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At a glance: The ONWARDS insulin icodec trials

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Advances in Therapy
Published in: Advances in Therapy 2/2021

01-02-2021 | Care | Review

Identifying Novel Biomarkers Ready for Evaluation in Low-Prevalence Populations for the Early Detection of Upper Gastrointestinal Cancers: A Systematic Review

Authors: Natalia Calanzani, Paige E. Druce, Claudia Snudden, Kristi M. Milley, Rachel Boscott, Dawnya Behiyat, Smiji Saji, Javiera Martinez-Gutierrez, Jasmeen Oberoi, Garth Funston, Mike Messenger, Jon Emery, Fiona M. Walter

Published in: Advances in Therapy | Issue 2/2021

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Abstract

Introduction

Detecting upper gastrointestinal (GI) cancers in primary care is challenging, as cancer symptoms are common, often non-specific, and most patients presenting with these symptoms will not have cancer. Substantial investment has been made to develop biomarkers for cancer detection, but few have reached routine clinical practice. We aimed to identify novel biomarkers for upper GI cancers which have been sufficiently validated to be ready for evaluation in low-prevalence populations.

Methods

We systematically searched MEDLINE, Embase, Emcare, and Web of Science for studies published in English from January 2000 to October 2019 (PROSPERO registration CRD42020165005). Reference lists of included studies were assessed. Studies had to report on second measures of diagnostic performance (beyond discovery phase) for biomarkers (single or in panels) used to detect pancreatic, oesophageal, gastric, and biliary tract cancers. We included all designs and excluded studies with less than 50 cases/controls. Data were extracted on types of biomarkers, populations and outcomes. Heterogeneity prevented pooling of outcomes.

Results

We identified 149 eligible studies, involving 22,264 cancer cases and 49,474 controls. A total of 431 biomarkers were identified (183 microRNAs and other RNAs, 79 autoantibodies and other immunological markers, 119 other proteins, 36 metabolic markers, 6 circulating tumour DNA and 8 other). Over half (n = 231) were reported in pancreatic cancer studies. Only 35 biomarkers had been investigated in at least two studies, with reported outcomes for that individual marker for the same tumour type. Apolipoproteins (apoAII-AT and apoAII-ATQ), and pepsinogens (PGI and PGII) were the most promising biomarkers for pancreatic and gastric cancer, respectively.

Conclusion

Most novel biomarkers for the early detection of upper GI cancers are still at an early stage of matureness. Further evidence is needed on biomarker performance in low-prevalence populations, in addition to implementation and health economic studies, before extensive adoption into clinical practice can be recommended.
Appendix
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Literature
1.
Arnold M, Abnet CC, Neale RE, et al. Global burden of 5 major types of gastrointestinal cancer. Gastroenterology. 2020;159(1):335–49.PubMedCrossRef
2.
Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.CrossRefPubMed
3.
Emery JD, Shaw K, Williams B, et al. The role of primary care in early detection and follow-up of cancer. Nat Rev Clin Oncol. 2014;11(1):38–48.PubMedCrossRef
4.
Rubin G, Berendsen A, Crawford SM, et al. The expanding role of primary care in cancer control. Lancet Oncol. 2015;16(12):1231–72.PubMedCrossRef
5.
Rubin G, Walter F, Emery J, et al. Reimagining the diagnostic pathway for gastrointestinal cancer. Nat Rev Gastroenterol Hepatol. 2018;15(3):181–8.PubMedCrossRef
6.
Hamilton W. The CAPER studies: five case-control studies aimed at identifying and quantifying the risk of cancer in symptomatic primary care patients. Br J Cancer. 2009;101(Suppl 2):S80–6.PubMedPubMedCentralCrossRef
7.
Rasmussen S, Haastrup PF, Balasubramaniam K, et al. Predictive values of upper gastrointestinal cancer alarm symptoms in the general population: a nationwide cohort study. BMC Cancer. 2018;18(1):440.PubMedPubMedCentralCrossRef
8.
Hippisley-Cox J, Coupland C. Development and validation of risk prediction algorithms to estimate future risk of common cancers in men and women: prospective cohort study. BMJ Open. 2015;5(3):e007825.PubMedPubMedCentralCrossRef
9.
10.
Lyratzopoulos G, Wardle J, Rubin G. Rethinking diagnostic delay in cancer: how difficult is the diagnosis? BMJ Br Med J. 2014;349:g7400.CrossRef
11.
12.
Ioannidis JPA, Bossuyt PMM. Waste, leaks, and failures in the biomarker pipeline. Clin Chem. 2017;63(5):963–72.PubMedCrossRef
13.
Worm Ørntoft MB. Review of blood-based colorectal cancer screening: how far are circulating cell-free DNA methylation markers from clinical implementation? Clin Colorectal Cancer. 2018;17(2):e415–33.PubMedCrossRef
14.
15.
Walter FM, Thompson MJ, Wellwood I, et al. Evaluating diagnostic strategies for early detection of cancer: the CanTest framework. BMC Cancer. 2019;19(1):586.PubMedPubMedCentralCrossRef
16.
Rutjes AW, Reitsma JB, Vandenbroucke JP, et al. Case-control and two-gate designs in diagnostic accuracy studies. Clin Chem. 2005;51(8):1335–41.PubMedCrossRef
17.
Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.PubMedPubMedCentralCrossRef
18.
Pepe MS, Etzioni R, Feng Z, et al. Phases of biomarker development for early detection of cancer. J Natl Cancer Inst. 2001;93(14):1054–61.PubMedCrossRef
19.
Uttley L, Whiteman BL, Woods HB, et al. Building the evidence base of blood-based biomarkers for early detection of cancer: a rapid systematic mapping review. EBioMedicine. 2016;10:164–73.PubMedPubMedCentralCrossRef
20.
21.
Whiting PF, Rutjes AW, Westwood ME, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155(8):529–36.CrossRefPubMed
22.
Popay J, Roberts H, Sowden A, et al. Guidance on the conduct of narrative synthesis in systematic reviews. a product from the ESRC methods programme: ESRC Methods Programme; 2006.
23.
Cai H, Yuan Y, Hao YF, et al. Plasma microRNAs serve as novel potential biomarkers for early detection of gastric cancer. Med Oncol. 2013;30(1):452.PubMedCrossRef
24.
Chen T, Sun L, He C, et al. Serum OPN expression for identification of gastric cancer and atrophic gastritis and its influencing factors. PLoS ONE. 2014;9(12):e114005.PubMedPubMedCentralCrossRef
25.
Chen C, Chen Q, Zhao Q, et al. Value of combined detection of serum CEA, CA72-4, CA19-9, CA15-3 and CA12-5 in the diagnosis of gastric cancer. Ann Clin Lab Sci. 2017;47(3):260–3.PubMed
26.
Chung HW, Kim JJ, Choi JI, et al. A disintegrin and metalloproteinase 8 as a potential blood biomarker for early diagnosis of gastric cancer. Yonsei Med J. 2019;60(8):713–9.PubMedPubMedCentralCrossRef
27.
Ding J, Che C, Liang YY, et al. Serum long non-coding RNA signatures serve as novel noninvasive biomarkers for diagnosis and prognosis of gastric cancer. Int J Clin Exp Pathol. 2017;10(5):5227–39.
28.
Dong X, Wang G, Zhang G, et al. The endothelial lipase protein is promising urinary biomarker for diagnosis of gastric cancer. Diagn Pathol. 2013;8:45.PubMedPubMedCentralCrossRef
29.
Gantuya B, Oyuntsetseg K, Bolor D, et al. Evaluation of serum markers for gastric cancer and its precursor diseases among high incidence and mortality rate of gastric cancer area. Gastric Cancer. 2019;22(1):104–12.PubMedCrossRef
30.
Gwak HK, Lee JH, Park SG. Preliminary evaluation of clinical utility of CYFRA 21–1, CA 72–4, NSE, CA19-9 and CEA in stomach cancer. Asian Pac J Cancer Prev. 2014;15(12):4933–8.PubMedCrossRef
31.
He CZ, Zhang KH, Li Q, et al. Combined use of AFP, CEA, CA125 and CAl9-9 improves the sensitivity for the diagnosis of gastric cancer. BMC Gastroenterol. 2013;13:87.PubMedPubMedCentralCrossRef
32.
Hoshino I, Nagata M, Takiguchi N, et al. Panel of autoantibodies against multiple tumor-associated antigens for detecting gastric cancer. Cancer Sci. 2017;108(3):308–15.PubMedPubMedCentralCrossRef
33.
Huang Z, Zhang X, Lu H, et al. Serum trefoil factor 3 is a promising non-invasive biomarker for gastric cancer screening: a monocentric cohort study in China. BMC Gastroenterol. 2014;14(1):74.PubMedPubMedCentralCrossRef
34.
Huang S, Wang J, Li J, et al. Serum microRNA expression profile as a diagnostic panel for gastric cancer. Jpn J Clin Oncol. 2016;46(9):811–8.PubMedCrossRef
35.
Huang Z, Zhu D, Wu L, et al. Six serum-based miRNAs as potential diagnostic biomarkers for gastric cancer. Cancer Epidemiol Biomarkers Prev. 2017;26(2):188–96.PubMedCrossRef
36.
Iwasaki H, Shimura T, Yamada T, et al. A novel urinary microRNA biomarker panel for detecting gastric cancer. J Gastroenterol. 2019;25:25.
37.
Ji B, Huang Y, Gu T, et al. Potential diagnostic and prognostic value of plasma long noncoding RNA LINC00086 and miR-214 expression in gastric cancer. Cancer Biomark. 2019;24(2):249–55.PubMedCrossRef
38.
39.
Kaise M, Miwa J, Tashiro J, et al. The combination of serum trefoil factor 3 and pepsinogen testing is a valid non-endoscopic biomarker for predicting the presence of gastric cancer: a new marker for gastric cancer risk. J Gastroenterol. 2011;46(6):736–45.PubMedCrossRef
40.
Kang JM, Kim N, Yoo JY, et al. The role of serum pepsinogen and gastrin test for the detection of gastric cancer in Korea. Helicobacter. 2008;13(2):146–56.PubMedCrossRef
41.
Kikuchi R, Abe Y, Iijima K, et al. Low serum levels of pepsinogen and gastrin 17 are predictive of extensive gastric atrophy with high-risk of early gastric cancer. Tohoku J Exp Med. 2011;223(1):35–44.PubMedCrossRef
42.
Kim M, Kim HJ, Choi BY, et al. Identification of potential serum biomarkers for gastric cancer by a novel computational method, multiple normal tissues corrected differential analysis. Clin Chim Acta. 2012;413(3):428–33.PubMedCrossRef
43.
Kurilovich S, Belkovets A, Reshetnikov O, et al. Stomach-specific biomarkers (GastroPanel) can predict the development of gastric cancer in a caucasian population: a longitudinal nested case–control study in Siberia. Anticancer Res. 2016;36(1):247–53.PubMed
44.
Li BS, Zhao YL, Guo G, et al. Plasma microRNAs, miR-223, miR-21 and miR-218, as novel potential biomarkers for gastric cancer detection. PLoS ONE. 2012;7(7):e41629.PubMedPubMedCentralCrossRef
45.
Li Q, Shao Y, Zhang X, et al. Plasma long noncoding RNA protected by exosomes as a potential stable biomarker for gastric cancer. Tumour Biol. 2015;36(3):2007–12.PubMedCrossRef
46.
Li FX, Guo YN, Liu JT, et al. The significance of elevated plasma expression of microRNA 106b similar to 25 clusters in gastric cancer. PLoS ONE. 2017;12(5):12.
47.
Li F, Yoshizawa JM, Kim KM, et al. Discovery and validation of salivary extracellular RNA biomarkers for noninvasive detection of gastric cancer. Clin Chem. 2018;64(10):1513–21.PubMedPubMedCentralCrossRef
48.
49.
Lim JB, Kim DK, Chung HW. Clinical significance of serum thymus and activation-regulated chemokine in gastric cancer: potential as a serum biomarker. Cancer Sci. 2014;105(10):1327–33.PubMedPubMedCentralCrossRef
50.
Lim JB, Chung HW. Serum ENA78/CXCL5, SDF-1/CXCL12, and their combinations as potential biomarkers for prediction of the presence and distant metastasis of primary gastric cancer. Cytokine. 2015;73(1):16–22.PubMedCrossRef
51.
Lin LY, Yang L, Zeng Q, et al. Tumor-originated exosomal lncUEGC1 as a circulating biomarker for early-stage gastric cancer. Mol Cancer. 2018;17(1):84.PubMedPubMedCentralCrossRef
52.
Liu R, Zhang C, Hu Z, et al. A five-microRNA signature identified from genome-wide serum microRNA expression profiling serves as a fingerprint for gastric cancer diagnosis. Eur J Cancer. 2011;47(5):784–91.PubMedCrossRef
53.
Liu WL, Liu D, Cheng K, et al. Evaluating the diagnostic and prognostic value of circulating cathepsin S in gastric cancer. Oncotarget. 2016;7(19):28124–38.PubMedPubMedCentralCrossRef
54.
Liu J, Wang J, Song Y, et al. A panel consisting of three novel circulating lncRNAs, is it a predictive tool for gastric cancer? J Cell Mol Med. 2018;22(7):3605–13.PubMedPubMedCentralCrossRef
55.
Meistere I, Werner S, Zayakin P, et al. The prevalence of cancer-associated autoantibodies in patients with gastric cancer and progressive grades of premalignant lesions. Cancer Epidemiol Biomarkers Prev. 2017;26(10):1564.PubMedCrossRef
56.
Mroczko B, Groblewska M, Lukaszewicz-Zajac M, et al. Pre-treatment serum and plasma levels of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) in gastric cancer patients. Clin Chem Lab Med. 2009;47(9):1133–9.PubMedCrossRef
57.
Ning S, Wei W, Li J, et al. Clinical significance and diagnostic capacity of serum TK1, CEA, CA 19–9 and CA 72–4 levels in gastric and colorectal cancer patients. J Cancer. 2018;9(3):494–501.PubMedPubMedCentralCrossRef
58.
Oue N, Sentani K, Noguchi T, et al. Serum olfactomedin 4 (GWI 12, hGC4) in combination with Reg IV is a highly sensitive biomarker for gastric cancer patients. Int J Cancer. 2009;125(10):2383–92.PubMedCrossRef
59.
Pan YQ, Ruan YY, Peng JB, et al. Diagnostic significance of soluble human leukocyte antigen-G for gastric cancer. Hum Immunol. 2016;77(4):317–24.PubMedCrossRef
60.
Park KU, Lee HE, Nam SK, et al. The quantification of HER2 and MYC gene fragments in cell-free plasma as putative biomarkers for gastric cancer diagnosis. Clin Chem Lab Med. 2014;52(7):1033–40.PubMedCrossRef
61.
Parvaee P, Sarmadian H, Khansarinejad B, et al. Plasma level of microRNAs, MiR-107, MiR-194 and MiR-210 as potential biomarkers for diagnosis intestinal-type gastric cancer in human. Asian Pac J Cancer Prev. 2019;20(5):1421–6.PubMedPubMedCentralCrossRef
62.
Qin J, Wang S, Shi J, et al. Using recursive partitioning approach to select tumor-associated antigens in immunodiagnosis of gastric adenocarcinoma. Cancer Sci. 2019;110(6):1829–41.PubMedPubMedCentralCrossRef
63.
64.
Song MY, Pan KF, Su HJ, et al. Identification of serum microRNAs as novel non-invasive biomarkers for early detection of gastric cancer. PLoS ONE. 2012;7(3):e33608.PubMedPubMedCentralCrossRef
65.
Su Y, Shen J, Qian H, et al. Diagnosis of gastric cancer using decision tree classification of mass spectral data. Cancer Sci. 2007;98(1):37–43.PubMedCrossRef
66.
Sun L, Tu H, Chen T, et al. Three-dimensional combined biomarkers assay could improve diagnostic accuracy for gastric cancer. Sci Rep. 2017;7(1):11621.PubMedPubMedCentralCrossRef
67.
Tsalikidis C, Papachristou F, Pitiakoudis M, et al. Soluble E-cadherin as a diagnostic and prognostic marker in gastric carcinoma. Folia Med (Plovdiv). 2013;55(3–4):26–32.CrossRef
68.
Wang CS, Wu TL, Tsao KC, et al. Serum TIMP-1 in gastric cancer patients: a potential prognostic biomarker. Ann Clin Lab Sci. 2006;36(1):23–30.PubMed
69.
Wang J, Zhang H, Zhou X, et al. Five serum-based miRNAs were identified as potential diagnostic biomarkers in gastric cardia adenocarcinoma. Cancer Biomark. 2018;23(2):193–203.PubMedCrossRef
70.
Wang S, Qin J, Ye H, et al. Using a panel of multiple tumor-associated antigens to enhance autoantibody detection for immunodiagnosis of gastric cancer. Oncoimmunology. 2018;7(8):e1452582.PubMedPubMedCentralCrossRef
71.
Wang M, Wang J, Jiang H. Diagnostic value of apolipoprotein C-I, transthyretin and apolipoprotein C-III in gastric cancer. Oncol Lett. 2019;17(3):3227–32.PubMedPubMedCentral
72.
Werner S, Chen H, Butt J, et al. Evaluation of the diagnostic value of 64 simultaneously measured autoantibodies for early detection of gastric cancer. Sci Rep. 2016;6:25467.PubMedPubMedCentralCrossRef
73.
Wu J, Li G, Yao Y, et al. MicroRNA-421 is a new potential diagnosis biomarker with higher sensitivity and specificity than carcinoembryonic antigen and cancer antigen 125 in gastric cancer. Biomarkers. 2015;20(1):58–63.PubMedCrossRef
74.
Wu X, Wang Q, Zhu Z, et al. Serum cell free DNA by branched DNA in patients with gastric cancer. Int J Clin Exp Med. 2016;9(6):11175–83.
75.
Wu Y, Jiang M, Qin Y, et al. Single and combined use of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and carcinoembryonic antigen in diagnosing gastric cancer. Clin Chim Acta. 2018;481:20–4.PubMedCrossRef
76.
Yanaoka K, Oka M, Mukoubayashi C, et al. Cancer high-risk subjects identified by serum pepsinogen tests: outcomes after 10-year follow-up in asymptomatic middle-aged males. Cancer Epidemiol Biomarkers Prev. 2008;17(4):838–45.PubMedCrossRef
77.
Yang JJ, Yang JH, Kim J, et al. Soluble c-Met protein as a susceptible biomarker for gastric cancer risk: a nested case-control study within the Korean multicenter cancer cohort. Int J Cancer. 2013;132(9):2148–56.PubMedCrossRef
78.
Yang Z, Sun Y, Liu R, et al. Plasma long noncoding RNAs PANDAR, FOXD2-AS1, and SMARCC2 as potential novel diagnostic biomarkers for gastric cancer. Cancer Manag Res. 2019;11:6175–84.PubMedPubMedCentralCrossRef
79.
80.
Yun ZY, Li N, Zhang X, et al. Mean platelet volume, platelet distribution width and carcinoembryonic antigen to discriminate gastric cancer from gastric ulcer. Oncotarget. 2017;8(37):62600–5.PubMedPubMedCentralCrossRef
81.
Zayakin P, Ancans G, Silina K, et al. Tumor-associated autoantibody signature for the early detection of gastric cancer. Int J Cancer. 2013;132(1):137–47.PubMedCrossRef
82.
Zhang Y, Qiu L, Wang Y, et al. Unsaturated free fatty acids: a potential biomarker panel for early detection of gastric cancer. Biomarkers. 2014a;19(8):667–73.PubMedCrossRef
83.
Zhang KC, Xi HQ, Cui JX, et al. Hemolysis-free plasma miR-214 as novel biomarker of gastric cancer and is correlated with distant metastasis. Am J Cancer Res. 2015;5(2):821–9.PubMedPubMedCentral
84.
Zhang K, Shi H, Xi H, et al. Genome-wide lncRNA microarray profiling identifies novel circulating lncRNAs for detection of gastric cancer. Theranostics. 2017;7(1):213–27.PubMedPubMedCentralCrossRef
85.
Zhou X, Ji G, Chen H, et al. Clinical role of circulating miR-223 as a novel biomarker in early diagnosis of cancer patients. Int J Clin Exp Med. 2015;8(9):16890–8.PubMedPubMedCentral
86.
87.
Zhou X, Yin C, Dang Y, et al. Identification of the long non-coding RNA H19 in plasma as a novel biomarker for diagnosis of gastric cancer. Sci Rep. 2015;5:11516.PubMedPubMedCentralCrossRef
88.
Akita H, Ritchie SA, Takemasa I, et al. Serum metabolite profiling for the detection of pancreatic cancer: results of a large independent validation study. Pancreas. 2016;45(10):1418–23.PubMedCrossRef
89.
Balasenthil S, Huang Y, Liu S, et al. A plasma biomarker panel to identify surgically resectable early-stage pancreatic cancer. J Natl Cancer Inst. 2017;109(8):01.CrossRef
90.
91.
92.
Capello M, Bantis LE, Scelo G, et al. Sequential validation of blood-based protein biomarker candidates for early-stage pancreatic cancer. J Natl Cancer Inst. 2017;109(4):01.CrossRef
93.
Chung HW, Lim JB. Clinical significance of serum levels of immune-associated molecules, uric acid and soluble MHC class I chain-related molecules A and B, as diagnostic tumor markers for pancreatic ductal adenocarcinoma. Cancer Sci. 2011;102(9):1673–9.PubMedCrossRef
94.
Chung HW, Jang S, Lim JB. Clinical implications and diagnostic usefulness of correlation between soluble major histocompatibility complex class I chain-related molecule a and protumorigenic cytokines in pancreatic ductal adenocarcinoma. Cancer. 2013;119(1):233–44.PubMedCrossRef
95.
Deng T, Yuan Y, Zhang C, et al. Identification of circulating MiR-25 as a potential biomarker for pancreatic cancer diagnosis. Cell Physiol Biochem. 2016;39(5):1716–22.PubMedCrossRef
96.
Duraker N, Hot S, Polat Y, et al. CEA, CA 19–9, and CA 125 in the differential diagnosis of benign and malignant pancreatic diseases with or without jaundice. J Surg Oncol. 2007;95(2):142–7.PubMedCrossRef
97.
Firpo MA, Gay DZ, Granger SR, et al. Improved diagnosis of pancreatic adenocarcinoma using haptoglobin and serum amyloid A in a panel screen. World J Surg. 2009;33(4):716–22.PubMedPubMedCentralCrossRef
98.
Fukutake N, Ueno M, Hiraoka N, et al. A novel multivariate index for pancreatic cancer detection based on the plasma free amino acid profile. PLoS ONE. 2015;10(7):e0132223.PubMedPubMedCentralCrossRef
99.
Gao L, He SB, Li DC. Effects of miR-16 plus CA19-9 detections on pancreatic cancer diagnostic performance. Clin Lab. 2014;60(1):73–7.PubMed
100.
David VG, David EM, Zhiliang Y, et al. New MUC1 serum immunoassay differentiates pancreatic cancer from pancreatitis. J Clin Oncol. 2006;24(2):252–8.CrossRef
101.
Gold DV, Gaedcke J, Ghadimi BM, et al. PAM4 enzyme immunoassay alone and in combination with CA 19–9 for the detection of pancreatic adenocarcinoma. Cancer. 2013;119(3):522–8.PubMedCrossRef
102.
Groblewska M, Mroczko B, Wereszczyńska-Siemiatkowska U, et al. Serum levels of granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF) in pancreatic cancer patients. Clin Chem Lab Med. 2007;45(1):30–4.PubMedCrossRef
103.
Guo X, Lv XH, Fang C, et al. Dysbindin as a novel biomarker for pancreatic ductal adenocarcinoma identified by proteomic profiling. Int J Cancer. 2016;139(8):1821–9.PubMedCrossRef
104.
Honda K, Okusaka T, Felix K, et al. Altered plasma apolipoprotein modifications in patients with pancreatic cancer: protein characterization and multi-institutional validation. PLoS ONE. 2012;7(10):e46908.PubMedPubMedCentralCrossRef
105.
Honda K, Kobayashi M, Okusaka T, et al. Plasma biomarker for detection of early stage pancreatic cancer and risk factors for pancreatic malignancy using antibodies for apolipoprotein-AII isoforms. Sci Rep. 2015;5:15921.PubMedPubMedCentralCrossRef
106.
Honda K, Katzke VA, Husing A, et al. CA19-9 and apolipoprotein-A2 isoforms as detection markers for pancreatic cancer: a prospective evaluation. Int J Cancer. 2019;144(8):1877–87.PubMedCrossRef
107.
108.
Kaur S, Smith LM, Patel A, et al. A combination of MUC5AC and CA19-9 improves the diagnosis of pancreatic cancer: a multicenter study. Am J Gastroenterol. 2017;112(1):172–83.PubMedCrossRef
109.
Kim J, Bamlet WR, Oberg AL, et al. Detection of early pancreatic ductal adenocarcinoma with thrombospondin-2 and CA19-9 blood markers. Sci Transl Med. 2017;9(398):12.CrossRef
110.
Kuwatani M, Kawakami H, Kubota Y, et al. Verification of the effectiveness of fucosylated haptoglobin as a pancreatic cancer marker in clinical diagnosis. Pancreatology. 2019;19(4):569–77.PubMedCrossRef
111.
Le Calvez-Kelm F, Foll M, Wozniak MB, et al. KRAS mutations in blood circulating cell-free DNA: a pancreatic cancer case-control. Oncotarget. 2016;7(48):78827–40.PubMedPubMedCentralCrossRef
112.
Lee JH. The feasibility of serum multiple tumor markers test between patients with primary pancreatic cancer and those with benign pancreatic cystic disease. Clin Lab. 2019;65(10):01.
113.
Liao WC, Wu MS, Wang HP, et al. Serum heat shock protein 27 is increased in chronic pancreatitis and pancreatic carcinoma. Pancreas. 2009;38(4):422–6.PubMedCrossRef
114.
Liu J, Gao J, Du Y, et al. Combination of plasma microRNAs with serum CA19-9 for early detection of pancreatic cancer. Int J Cancer. 2012;131(3):683–91.PubMedCrossRef
115.
Liu R, Chen X, Du Y, et al. Serum microRNA expression profile as a biomarker in the diagnosis and prognosis of pancreatic cancer. Clin Chem. 2012;58(3):610–8.PubMedCrossRef
116.
117.
Matsubara J, Honda K, Ono M, et al. Reduced plasma level of CXC chemokine ligand 7 in patients with pancreatic cancer. Cancer Epidemiol Biomarkers Prev. 2011;20(1):160–71.PubMedCrossRef
118.
Mayerle J, Kalthoff H, Reszka R, et al. Metabolic biomarker signature to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis. Gut. 2018;67(1):128–37.CrossRefPubMed
119.
Mellby LD, Nyberg AP, Johansen JS, et al. Serum biomarker signature-based liquid biopsy for diagnosis of early-stage pancreatic cancer. J Clin Oncol. 2018;36(28):2887–94.PubMedPubMedCentralCrossRef
120.
Mizuno S, Isayama H, Nakai Y, et al. Diagnostic yield of the plasma free amino acid index for pancreatic cancer in patients with diabetes mellitus. Pancreatology. 2019;19(5):695–8.PubMedCrossRef
121.
O’Brien DP, Sandanayake NS, Jenkinson C, et al. Serum CA19-9 is significantly upregulated up to 2 years before diagnosis with pancreatic cancer: implications for early disease detection. Clin Cancer Res. 2015;21(3):622–31.PubMedCrossRef
122.
Park HD, Kang ES, Kim JW, et al. Serum CA19-9, cathepsin D, and matrix metalloproteinase-7 as a diagnostic panel for pancreatic ductal adenocarcinoma. Proteomics. 2012;12(23–24):3590–7.PubMedCrossRef
123.
Park J, Lee E, Park KJ, et al. Large-scale clinical validation of biomarkers for pancreatic cancer using a mass spectrometry-based proteomics approach. Oncotarget. 2017;8(26):42761–71.PubMedPubMedCentralCrossRef
124.
Peng HY, Chang MC, Hu CM, et al. Thrombospondin-2 is a highly specific diagnostic marker and is associated with prognosis in pancreatic cancer. Ann Surg Oncol. 2019;26(3):807–14.PubMedCrossRef
125.
Poruk KE, Firpo MA, Scaife CL, et al. Serum osteopontin and tissue inhibitor of metalloproteinase 1 as diagnostic and prognostic biomarkers for pancreatic adenocarcinoma. Pancreas. 2013;42(2):193–7.PubMedPubMedCentralCrossRef
126.
Ritchie SA, Chitou B, Zheng Q, et al. Pancreatic cancer serum biomarker PC-594: diagnostic performance and comparison to CA19-9. World J Gastroenterol. 2015;21(21):6604–12.PubMedPubMedCentralCrossRef
127.
Rychlíková J, Vecka M, Jáchymová M, et al. Osteopontin as a discriminating marker for pancreatic cancer and chronic pancreatitis. Cancer Biomark. 2016;17(1):55–65.PubMedCrossRef
128.
Sakai Y, Honda M, Matsui S, et al. Development of novel diagnostic system for pancreatic cancer, including early stages, measuring mRNA of whole blood cells. Cancer Sci. 2019;110(4):1364–88.PubMedPubMedCentralCrossRef
129.
Song J, Sokoll LJ, Pasay JJ, et al. Identification of serum biomarker panels for the early detection of pancreatic cancer. Cancer Epidemiol Biomarkers Prev. 2019;28(1):174–82.PubMedCrossRef
130.
131.
Talar-Wojnarowska R, Gasiorowska A, Olakowski M, et al. Clinical value of serum neopterin, tissue polypeptide-specific antigen and CA19-9 levels in differential diagnosis between pancreatic cancer and chronic pancreatitis. Pancreatology. 2010;10(6):689–94.PubMedCrossRef
132.
Tavano F, Gioffreda D, Valvano MR, et al. Droplet digital PCR quantification of miR-1290 as a circulating biomarker for pancreatic cancer. Sci Rep. 2018;8(1):16389.PubMedPubMedCentralCrossRef
133.
Ward DG, Wei W, Buckels J, et al. Detection of pancreatic adenocarcinoma using circulating fragments of fibrinogen. Eur J Gastroenterol Hepatol. 2010;22(11):1358–63.PubMedCrossRef
134.
Xu J, Cao Z, Liu W, et al. Plasma miRNAs effectively distinguish patients with pancreatic cancer from controls: a multicenter study. Ann Surg. 2016;263(6):1173–9.PubMedCrossRef
135.
Zhang P, Zou M, Wen X, et al. Development of serum parameters panels for the early detection of pancreatic cancer. Int J Cancer. 2014;134(11):2646–55.PubMedCrossRef
136.
Zhang Y, Qiu L, Wang Y, et al. High-throughput and high-sensitivity quantitative analysis of serum unsaturated fatty acids by chip-based nanoelectrospray ionization-Fourier transform ion cyclotron resonance mass spectrometry: early stage diagnostic biomarkers of pancreatic cancer. Analyst. 2014b;139(7):1697–706.PubMedCrossRef
137.
Zhong A, Qin R, Qin W, et al. Diagnostic significance of serum IgG galactosylation in CA19-9-negative pancreatic carcinoma patients. Front Oncol. 2019;9:114.PubMedPubMedCentralCrossRef
138.
Zhou YF, Xu LX, Huang LY, et al. Combined detection of serum UL16-binding protein 2 and macrophage inhibitory cytokine-1 improves early diagnosis and prognostic prediction of pancreatic cancer. Oncol Lett. 2014;8(5):2096–102.PubMedPubMedCentralCrossRef
139.
Zhou CY, Dong YP, Sun X, et al. High levels of serum glypican-1 indicate poor prognosis in pancreatic ductal adenocarcinoma. Cancer Med. 2018;7(11):5525–33.PubMedPubMedCentralCrossRef
140.
Zhou X, Lu Z, Wang T, et al. Plasma miRNAs in diagnosis and prognosis of pancreatic cancer: a miRNA expression analysis. Gene. 2018;673:181–93.PubMedCrossRef
141.
Bagaria B, Sood S, Sharma R, et al. Diagnostic precision of carcinoembryonic antigen level in esophageal carcinoma. Biomed Res (Aligarh). 2013a;24(3):353–8.
142.
Bai Y, Lin H, Fang Z, et al. Plasma microRNA-19a as a potential biomarker for esophageal squamous cell carcinoma diagnosis and prognosis. Biomark Med. 2017;11(5):431–41.PubMedCrossRef
143.
Bagaria B, Bagaria A, Singh M, et al. Diagnostic sensitivity of serum carcinoembryonic antigen, carbohydrate antigen 19–9, alpha-fetoprotein, and beta-human chorionic gonadotropin in esophageal carcinoma (receiver operating characteristic curve analysis). Clin Cancer Investig J. 2015;4(3):312–7.
144.
Brockmann JG, St Nottberg H, Glodny B, et al. Analysis of serum CYFRA 21–1 concentrations in patients with esophageal cancer. Anticancer Res. 2000;20(6D):4899–904.PubMed
145.
Huang Z, Zhang L, Zhu D, et al. A novel serum microRNA signature to screen esophageal squamous cell carcinoma. Cancer Med. 2017;6(1):109–19.PubMedCrossRef
146.
Jia K, Li W, Wang F, et al. Novel circulating peptide biomarkers for esophageal squamous cell carcinoma revealed by a magnetic bead-based MALDI-TOFMS assay. Oncotarget. 2016;7(17):23569–80.PubMedPubMedCentralCrossRef
147.
Liao Y, Xing S, Xu B, et al. Evaluation of the circulating level of fibroblast activation protein alpha for diagnosis of esophageal squamous cell carcinoma. Oncotarget. 2017;8(18):30050–62.PubMedPubMedCentralCrossRef
148.
Lukaszewicz-Zajac M, Mroczko B, Kozlowski M, et al. Stem cell factor in the serum of patients with esophageal cancer in relation to its histological types. Arch Med Sci. 2017;13(6):1357–64.PubMedCrossRef
149.
Lv H, He Z, Wang H, et al. Differential expression of miR-21 and miR-75 in esophageal carcinoma patients and its clinical implication. Am J Transl Res. 2016;8(7):3288–98.PubMedPubMedCentral
150.
Pan J, Zheng QZ, Li Y, et al. Discovery and validation of a serologic autoantibody panel for early diagnosis of esophageal squamous cell carcinoma. Cancer Epidemiol Biomark Prev. 2019;28(9):1454–60.CrossRef
151.
Peng YH, Xu YW, Guo H, et al. Combined detection of serum Dickkopf-1 and its autoantibodies to diagnose esophageal squamous cell carcinoma. Cancer Med. 2016;5(7):1388–96.PubMedPubMedCentralCrossRef
152.
Sudo K, Kato K, Matsuzaki J, et al. Development and validation of an esophageal squamous cell carcinoma detection model by large-scale MicroRNA profiling. JAMA Netw Open. 2019;2(5):e194573.PubMedPubMedCentralCrossRef
153.
Wang C, Guan S, Liu F, et al. Prognostic and diagnostic potential of miR-146a in oesophageal squamous cell carcinoma. Br J Cancer. 2016;114(3):290–7.PubMedPubMedCentralCrossRef
154.
Xing S, Zheng X, Wei LQ, et al. Development and validation of a serum biomarker panel for the detection of esophageal squamous cell Carcinoma through RNA transcriptome sequencing. J Cancer. 2017;8(12):2346–55.PubMedPubMedCentralCrossRef
155.
Xu YW, Peng YH, Chen B, et al. Autoantibodies as potential biomarkers for the early detection of esophageal squamous cell carcinoma. Am J Gastroenterol. 2014;109(1):36–45.PubMedCrossRef
156.
Xu YW, Chen H, Guo HP, et al. Combined detection of serum autoantibodies as diagnostic biomarkers in esophagogastric junction adenocarcinoma. Gastric Cancer. 2019;22(3):546–57.PubMedCrossRef
157.
Yan L, Dong X, Gao J, et al. A novel rapid quantitative method reveals stathmin-1 as a promising marker for esophageal squamous cell carcinoma. Cancer Med. 2018;7(5):1802–13.PubMedPubMedCentralCrossRef
158.
Zhang T, Wang Q, Zhao D, et al. The oncogenetic role of microRNA-31 as a potential biomarker in oesophageal squamous cell carcinoma. Clin Sci. 2011;121(10):437–47.CrossRef
159.
Zhang B, Zhang Z, Zhang X, et al. Serological antibodies against LY6K as a diagnostic biomarker in esophageal squamous cell carcinoma. Biomarkers. 2012;17(4):372–8.PubMedCrossRef
160.
Zhang T, Zhao D, Wang Q, et al. MicroRNA-1322 regulates ECRG2 allele specifically and acts as a potential biomarker in patients with esophageal squamous cell carcinoma. Mol Carcinog. 2013;52(8):581–90.PubMedCrossRef
161.
Zhang HF, Qin JJ, Ren PF, et al. A panel of autoantibodies against multiple tumor-associated antigens in the immunodiagnosis of esophageal squamous cell cancer. Cancer Immunol Immunother. 2016;65(10):1233–42.PubMedCrossRef
162.
Zhang JB, Cao M, Chen J, et al. Serum anti-TOPO48 autoantibody as a biomarker for early diagnosis and prognosis in patients with esophageal squamous cell carcinoma. Clin Res Hepatol Gastroenterol. 2018;42(3):276–84.PubMedCrossRef
163.
Zheng X, Xing S, Liu XM, et al. Establishment of using serum YKL-40 and SCCA in combination for the diagnosis of patients with esophageal squamous cell carcinoma. BMC Cancer. 2014;14:490.PubMedPubMedCentralCrossRef
164.
Zhou SL, Yue WB, Fan ZM, et al. Autoantibody detection to tumor-associated antigens of P53, IMP1, P16, cyclin B1, P62, C-myc, Survivn, and Koc for the screening of high-risk subjects and early detection of esophageal squamous cell carcinoma. Dis Esophagus. 2014;27(8):790–7.PubMedCrossRef
165.
Deng YW, Zhong RH, Xie XY, et al. Serum CEA, CA125, CA19-9, and CA724 levels for the diagnosis and staging of cholangiocarcinoma. Biomed Res (Aligarh). 2017;28(3):1413–8.
166.
Leelawat K, Narong S, Wannaprasert J, et al. Prospective study of MMP7 serum levels in the diagnosis of cholangiocarcinoma. World J Gastroenterol. 2010;16(37):4697–703.PubMedPubMedCentralCrossRef
167.
Wang YF, Feng FL, Zhao XH, et al. Combined detection tumor markers for diagnosis and prognosis of gallbladder cancer. World J Gastroenterol. 2014;20(14):4085–92.PubMedPubMedCentralCrossRef
168.
Bagaria B, Sood S, Sharma R, et al. Comparative study of CEA and CA19-9 in esophageal, gastric and colon cancers individually and in combination (ROC curve analysis). Cancer Biol Med. 2013b;10(3):148–57.PubMedPubMedCentral
169.
Markar SR, Wiggins T, Antonowicz S, et al. Assessment of a noninvasive exhaled breath test for the diagnosis of oesophagogastric cancer. JAMA Oncol. 2018;4(7):970–6.PubMedPubMedCentralCrossRef
170.
Ren S, Zhang Z, Xu C, et al. Distribution of IgG galactosylation as a promising biomarker for cancer screening in multiple cancer types. Cell Res. 2016;26(8):963–6.PubMedPubMedCentralCrossRef
171.
Schneider J, Bitterlich N, Schulze G. Improved sensitivity in the diagnosis of gastro-intestinal tumors by fuzzy logic-based tumor marker profiles including the tumor M2-PK. Anticancer Res. 2005;25(3A):1507–15.PubMed
172.
Schultz NA, Dehlendorff C, Jensen BV, et al. MicroRNA biomarkers in whole blood for detection of pancreatic cancer. JAMA. 2014;311(4):392–404.PubMedCrossRef
173.
Huang Y-K, Yu J-C, Kang W-M, et al. Significance of serum pepsinogens as a biomarker for gastric cancer and atrophic gastritis screening: a systematic review and meta-analysis. PLoS ONE. 2015;10(11):e0142080.PubMedPubMedCentralCrossRef
174.
Cohen JD, Li L, Wang Y, et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science. 2018;359(6378):926.PubMedPubMedCentralCrossRef
175.
Bossuyt PM, Reitsma JB, Bruns DE, et al. STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. BMJ. 2015;351:h5527.PubMedPubMedCentralCrossRef
176.
Jüni P, Holenstein F, Sterne J, et al. Direction and impact of language bias in meta-analyses of controlled trials: empirical study. Int J Epidemiol. 2002;31(1):115–23.PubMedCrossRef
177.
Nussbaumer-Streit B, Klerings I, Dobrescu AI, et al. Excluding non-english publications from evidence-syntheses did not change conclusions: a meta-epidemiological study. J Clin Epidemiol. 2020;118:42–54.PubMedCrossRef
178.
Elliott JH, Turner T, Clavisi O, et al. Living systematic reviews: an emerging opportunity to narrow the evidence-practice gap. PLoS Med. 2014;11(2):e1001603.PubMedPubMedCentralCrossRef
179.
Westwood M, Lang S, Armstrong N, et al. Faecal immunochemical tests (FIT) can help to rule out colorectal cancer in patients presenting in primary care with lower abdominal symptoms: a systematic review conducted to inform new NICE DG30 diagnostic guidance. BMC Med. 2017;15(1):189.PubMedPubMedCentralCrossRef
180.
van Melle M, Yep Manzano SI, Wilson H, et al. Faecal immunochemical test to triage patients with abdominal symptoms for suspected colorectal cancer in primary care: review of international use and guidelines. Fam Pract. 2020 (epub 8 May 2020).
Metadata
Title
Identifying Novel Biomarkers Ready for Evaluation in Low-Prevalence Populations for the Early Detection of Upper Gastrointestinal Cancers: A Systematic Review
Authors
Natalia Calanzani
Paige E. Druce
Claudia Snudden
Kristi M. Milley
Rachel Boscott
Dawnya Behiyat
Smiji Saji
Javiera Martinez-Gutierrez
Jasmeen Oberoi
Garth Funston
Mike Messenger
Jon Emery
Fiona M. Walter
Publication date
01-02-2021
Publisher
Springer Healthcare
Keywords
Care
Biomarkers
Published in
Advances in Therapy / Issue 2/2021
Print ISSN: 0741-238X
Electronic ISSN: 1865-8652
DOI
https://doi.org/10.1007/s12325-020-01571-z

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