Top

Published in:

01-10-2020 | Gastric Cancer | Original Article

The Ratio of ssDNA to dsDNA in Circulating Cell-Free DNA Extract is a Stable Indicator for Diagnosis of Gastric Cancer

Authors: Xuewen Huang, Qi Zhao, Xianyuan An, Jie Pan, Lanjing Zhao, Lanfeng Shen, Yiqiu Xu, Dandan Yuan

Published in: Pathology & Oncology Research | Issue 4/2020

Abstract

Due to the different mechanisms of cell-free DNA production, the single-stranded DNA to double-stranded DNA ratio in blood maybe different between healthy individuals and gastric cancer (GC) patients. We aimed to explore the potential application of this ratio in GC diagnosis. The plasma cell-free DNA extracts from 118 healthy individuals and 106 GC patients were prepared. The levels of single-stranded DNA or double-stranded DNA in plasma, and the single-stranded DNA to double-stranded DNA ratio on the diagnostic efficiency for GC were assessed with ROC curve. The relationships between this ratio and the clinical characteristics of GC patients were analyzed. The ratios in 63 GC patients before and after surgery were compared. In healthy individuals, the single-stranded DNA to double-stranded DNA ratio was not affected by factors including age, gender and BMI, and subjected to normal distribution (P = 0.1090). GC patients had a lower value of this ratio than healthy individuals (P < 0.0001). Considering this ratio as a GC diagnostic indicator, the area under ROC curve (AUC) was 0.923[95% confidence interval (CI):0.880–0.955]. This ratio in unresectable GC was obviously lower than that in resectable GC (P = 0.0045). There was a rank correlation between this ratio and GC TNM staging (rho = −0.266, P = 0.0058), but it had no correlation with tumor size (r = 0.14, P = 0.145). Additionally, this ratio was not affected by hemolysis and repeated freeze-thaw of blood samples, and was significantly elevated after surgery(P < 0.0001). The single-stranded DNA to double-stranded DNA ratio in plasma is a stable non-invasive indicator for GC diagnosis.

Available only for authorised users

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424. https://doi.org/10.3322/caac.21492CrossRefPubMed

Herszenyi L, Tulassay Z (2010) Epidemiology of gastrointestinal and liver tumors. Eur Rev Med Pharmacol Sci 14(4):249–258PubMed

Kim YI, Kim YW, Choi IJ, Kim CG, Lee JY, Cho SJ, Eom BW, Yoon HM, Ryu KW, Kook MC (2015) Long-term survival after endoscopic resection versus surgery in early gastric cancers. Endoscopy 47(4):293–301. https://doi.org/10.1055/s-0034-1391284CrossRefPubMed

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J (2016) Cancer statistics in China, 2015. CA Cancer J Clin 66(2):115–132. https://doi.org/10.3322/caac.21338CrossRefPubMed

Zeng H, Zheng R, Guo Y, Zhang S, Zou X, Wang N, Zhang L, Tang J, Chen J, Wei K, Huang S, Wang J, Yu L, Zhao D, Song G, Chen J, Shen Y, Yang X, Gu X, Jin F, Li Q, Li Y, Ge H, Zhu F, Dong J, Guo G, Wu M, Du L, Sun X, He Y, Coleman MP, Baade P, Chen W, Yu XQ (2015) Cancer survival in China, 2003-2005: a population-based study. Int J Cancer 136(8):1921–1930. https://doi.org/10.1002/ijc.29227CrossRefPubMed

Ronellenfitsch U, Schwarzbach M, Hofheinz R, Kienle P, Kieser M, Slanger TE, Burmeister B, Kelsen D, Niedzwiecki D, Schuhmacher C, Urba S, van de Velde C, Walsh TN, Ychou M, Jensen K (2013) Preoperative chemo (radio) therapy versus primary surgery for gastroesophageal adenocarcinoma: systematic review with meta-analysis combining individual patient and aggregate data. Eur J Cancer 49(15):3149–3158. https://doi.org/10.1016/j.ejca.2013.05.029CrossRefPubMed

Alsina M, Miquel JM, Diez M, Castro S, Tabernero J (2019) How I treat gastric adenocarcinoma. ESMO Open 4(Suppl 2):e000521. https://doi.org/10.1136/esmoopen-2019-000521CrossRefPubMedPubMedCentral

Skrypkina I, Tsyba L, Onyshchenko K, Morderer D, Kashparova O, Nikolaienko O, Panasenko G, Vozianov S, Romanenko A, Rynditch A (2016) Concentration and methylation of cell-free DNA from blood plasma as diagnostic markers of renal Cancer. Dis Markers 2016:3693096. https://doi.org/10.1155/2016/3693096CrossRefPubMedPubMedCentral

Burnham P, Kim MS, Agbor-Enoh S, Luikart H, Valantine HA, Khush KK, De Vlaminck I (2016) Single-stranded DNA library preparation uncovers the origin and diversity of ultrashort cell-free DNA in plasma. Sci Rep 6:27859. https://doi.org/10.1038/srep27859CrossRefPubMedPubMedCentral

10.

Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, Bartlett BR, Wang H, Luber B, Alani RM, Antonarakis ES, Azad NS, Bardelli A, Brem H, Cameron JL, Lee CC, Fecher LA, Gallia GL, Gibbs P, Le D, Giuntoli RL, Goggins M, Hogarty MD, Holdhoff M, Hong SM, Jiao Y, Juhl HH, Kim JJ, Siravegna G, Laheru DA, Lauricella C, Lim M, Lipson EJ, Marie SK, Netto GJ, Oliner KS, Olivi A, Olsson L, Riggins GJ, Sartore-Bianchi A, Schmidt K, Shih LM, Oba-Shinjo SM, Siena S, Theodorescu D, Tie J, Harkins TT, Veronese S, Wang TL, Weingart JD, Wolfgang CL, Wood LD, Xing D, Hruban RH, Wu J, Allen PJ, Schmidt CM, Choti MA, Velculescu VE, Kinzler KW, Vogelstein B, Papadopoulos N, Diaz LA Jr (2014) Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med 6(224):224ra224. https://doi.org/10.1126/scitranslmed.3007094CrossRef

11.

Siravegna G, Marsoni S, Siena S, Bardelli A (2017) Integrating liquid biopsies into the management of cancer. Nat Rev Clin Oncol 14(9):531–548. https://doi.org/10.1038/nrclinonc.2017.14CrossRefPubMed

12.

Murtaza M, Dawson SJ, Tsui DW, Gale D, Forshew T, Piskorz AM, Parkinson C, Chin SF, Kingsbury Z, Wong AS, Marass F, Humphray S, Hadfield J, Bentley D, Chin TM, Brenton JD, Caldas C, Rosenfeld N (2013) Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature 497(7447):108–112. https://doi.org/10.1038/nature12065CrossRefPubMed

13.

Wu HC, Yang HI, Wang Q, Chen CJ, Santella RM (2017) Plasma DNA methylation marker and hepatocellular carcinoma risk prediction model for the general population. Carcinogenesis 38(10):1021–1028. https://doi.org/10.1093/carcin/bgx078CrossRefPubMedPubMedCentral

14.

Liao W, Mao Y, Ge P, Yang H, Xu H, Lu X, Sang X, Zhong S (2015) Value of quantitative and qualitative analyses of circulating cell-free DNA as diagnostic tools for hepatocellular carcinoma: a meta-analysis. Medicine (Baltimore) 94(14):e722. https://doi.org/10.1097/MD.0000000000000722CrossRef

15.

Volckmar AL, Sultmann H, Riediger A, Fioretos T, Schirmacher P, Endris V, Stenzinger A, Dietz S (2018) A field guide for cancer diagnostics using cell-free DNA: from principles to practice and clinical applications. Genes Chromosom Cancer 57(3):123–139. https://doi.org/10.1002/gcc.22517CrossRefPubMed

16.

Wei L, Wu W, Han L, Yu W, Du Y (2018) A quantitative analysis of the potential biomarkers of non-small cell lung cancer by circulating cell-free DNA. Oncol Lett 16(4):4353–4360. https://doi.org/10.3892/ol.2018.9198CrossRefPubMedPubMedCentral

17.

Ponti G, Maccaferri M, Manfredini M, Kaleci S, Mandrioli M, Pellacani G, Ozben T, Depenni R, Bianchi G, Pirola GM, Tomasi A (2018) The value of fluorimetry (Qubit) and spectrophotometry (NanoDrop) in the quantification of cell-free DNA (cfDNA) in malignant melanoma and prostate cancer patients. Clin Chim Acta 479:14–19. https://doi.org/10.1016/j.cca.2018.01.007CrossRefPubMed

18.

Lee TH, Montalvo L, Chrebtow V, Busch MP (2001) Quantitation of genomic DNA in plasma and serum samples: higher concentrations of genomic DNA found in serum than in plasma. Transfusion 41(2):276–282. https://doi.org/10.1046/j.1537-2995.2001.41020276.xCrossRefPubMed

19.

Macheret M, Halazonetis TD (2015) DNA replication stress as a hallmark of cancer. Annu Rev Pathol 10:425–448. https://doi.org/10.1146/annurev-pathol-012414-040424CrossRefPubMed

20.

Branzei D, Foiani M (2010) Maintaining genome stability at the replication fork. Nat Rev Mol Cell Biol 11(3):208–219. https://doi.org/10.1038/nrm2852CrossRefPubMed

21.

Zeman MK, Cimprich KA (2014) Causes and consequences of replication stress. Nat Cell Biol 16(1):2–9. https://doi.org/10.1038/ncb2897CrossRefPubMedPubMedCentral

22.

Gaillard H, Garcia-Muse T, Aguilera A (2015) Replication stress and cancer. Nat Rev Cancer 15(5):276–289. https://doi.org/10.1038/nrc3916CrossRefPubMed

23.

Thierry AR, El Messaoudi S, Gahan PB, Anker P, Stroun M (2016) Origins, structures, and functions of circulating DNA in oncology. Cancer Metastasis Rev 35(3):347–376. https://doi.org/10.1007/s10555-016-9629-xCrossRefPubMedPubMedCentral

24.

Snyder MW, Kircher M, Hill AJ, Daza RM, Shendure J (2016) Cell-free DNA comprises an in vivo nucleosome footprint that informs its tissues-of-origin. Cell 164(1–2):57–68. https://doi.org/10.1016/j.cell.2015.11.050CrossRefPubMedPubMedCentral

25.

Jahr S, Hentze H, Englisch S, Hardt D, Fackelmayer FO, Hesch RD, Knippers R (2001) DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res 61(4):1659–1665PubMed

26.

Zhang X, Wu Z, Shen Q, Li R, Jiang X, Wu J, Li D, Wang D, Zou C, Zhong Y, Cheng X (2019) Clinical significance of cell-free DNA concentration and integrity in serum of gastric cancer patients before and after surgery. Cell Mol Biol (Noisy-le-grand) 65(7):111–117CrossRef

27.

Park JL, Kim HJ, Choi BY, Lee HC, Jang HR, Song KS, Noh SM, Kim SY, Han DS, Kim YS (2012) Quantitative analysis of cell-free DNA in the plasma of gastric cancer patients. Oncol Lett 3(4):921–926. https://doi.org/10.3892/ol.2012.592CrossRefPubMedPubMedCentral

28.

You Y, Teng W, Wang J, Ma G, Ma A, Wang J, Liu P (2018) Hypertension and physical activity in middle-aged and older adults in China. Sci Rep 8(1):16098. https://doi.org/10.1038/s41598-018-34617-yCrossRefPubMedPubMedCentral

29.

Steevens J, Schouten LJ, Goldbohm RA, van den Brandt PA (2010) Alcohol consumption, cigarette smoking and risk of subtypes of oesophageal and gastric cancer: a prospective cohort study. Gut 59(1):39–48. https://doi.org/10.1136/gut.2009.191080CrossRefPubMed

30.

Sorber L, Zwaenepoel K, Deschoolmeester V, Roeyen G, Lardon F, Rolfo C, Pauwels P (2017) A comparison of cell-free DNA isolation kits: isolation and quantification of cell-free DNA in plasma. J Mol Diagn 19(1):162–168. https://doi.org/10.1016/j.jmoldx.2016.09.009CrossRefPubMed

31.

Sato A, Nakashima C, Abe T, Kato J, Hirai M, Nakamura T, Komiya K, Kimura S, Sueoka E, Sueoka-Aragane N (2018) Investigation of appropriate pre-analytical procedure for circulating free DNA from liquid biopsy. Oncotarget 9(61):31904–31914. https://doi.org/10.18632/oncotarget.25881CrossRefPubMedPubMedCentral

32.

Lippi G, Salvagno GL, Montagnana M, Brocco G, Guidi GC (2006) Influence of hemolysis on routine clinical chemistry testing. Clin Chem Lab Med 44(3):311–316. https://doi.org/10.1515/CCLM.2006.054CrossRefPubMed

33.

Chang Y, Tolani B, Nie X, Zhi X, Hu M, He B (2017) Review of the clinical applications and technological advances of circulating tumor DNA in cancer monitoring. Ther Clin Risk Manag 13:1363–1374. https://doi.org/10.2147/TCRM.S141991CrossRefPubMedPubMedCentral

34.

Mathurin P, Cadranel JF, Bouraya D, Bronstein JA, Collot G, Devergie B, Poynard T, Opolon P (1996) Marked increase in serum CA 19-9 level in patients with alcoholic cirrhosis: report of four cases. Eur J Gastroenterol Hepatol 8(11):1129–1131. https://doi.org/10.1097/00042737-199611000-00019CrossRefPubMed

35.

Shang X, Song C, Du X, Shao H, Xu D, Wang X (2017) The serum levels of tumor marker CA19-9, CEA, CA72-4, and NSE in type 2 diabetes without malignancy and the relations to the metabolic control. Saudi Med J 38(2):204–208. https://doi.org/10.15537/smj.2017.2.15649CrossRefPubMedPubMedCentral

36.

Zali H, Rezaei-Tavirani M, Azodi M (2011) Gastric cancer: prevention, risk factors and treatment. Gastroenterol Hepatol Bed Bench 4(4):175–185PubMedPubMedCentral

37.

Swets JA (1988) Measuring the accuracy of diagnostic systems. Science 240(4857):1285–1293. https://doi.org/10.1126/science.3287615CrossRefPubMed

Title: The Ratio of ssDNA to dsDNA in Circulating Cell-Free DNA Extract is a Stable Indicator for Diagnosis of Gastric Cancer
Authors: Xuewen Huang
Qi Zhao
Xianyuan An
Jie Pan
Lanjing Zhao
Lanfeng Shen
Yiqiu Xu
Dandan Yuan
Publication date: 01-10-2020
Publisher: Springer Netherlands
Keywords: Gastric Cancer
Gastric Cancer
Published in: Pathology & Oncology Research / Issue 4/2020
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI: https://doi.org/10.1007/s12253-020-00869-1

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2020

Aggressive Paraganglioma of the Urinary Bladder with Local Recurrence and Pelvic Metastasis

Aberrant Telomere Length in Circulating Cell-Free DNA as Possible Blood Biomarker with High Diagnostic Performance in Endometrial Cancer

Chromosome X riddle in SARS-CoV-2 (COVID-19) - related lung pathology

Loss of Interleukin-17RA Expression is Associated with Tumour Progression in Colorectal Carcinoma

Overexpression of Long Non-Coding RNA FGF14-AS2 Inhibits Colorectal Cancer Proliferation Via the RERG/Ras/ERK Signaling by Sponging microRNA-1288-3p

PD-L1 Expression in Small Cell and Large Cell Neuroendocrine Carcinomas of Lung: an Immunohistochemical Study with Review of Literature

Keynote webinar | Spotlight on antibody–drug conjugates in cancer