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Cancer Cell International
Published in: Cancer Cell International 1/2022

Open Access 01-12-2022 | Hepatocellular Carcinoma | Research

Establishment and validation of a novel prognostic model for non-virus-related hepatocellular carcinoma

Authors: Yu Jiang, Shulin Chen, Yaxian Wu, Yuanye Qu, Lina Jia, Qingxia Xu, Shuqin Dai, Ning Xue

Published in: Cancer Cell International | Issue 1/2022

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Abstract

Objective

The incidence of non-virus-related hepatocellular carcinoma (NV-HCC) in hepatocellular carcinoma (HCC) is steadily increasing. The aim of this study was to establish a prognostic model to evaluate the overall survival (OS) of NV-HCC patients.

Methods

Overall, 261 patients with NV-HCC were enrolled in this study. A prognostic model was developed by using LASSO-Cox regression analysis. The prognostic power was appraised by the concordance index (C-index), and the time-dependent receiver operating characteristic curve (TD-ROC). Kaplan–Meier (K–M) survival analysis was used to evaluate the predictive ability in the respective subgroups stratified by the prognostic model risk score. A nomogram for survival prediction was established by integrating the prognostic model, TNM stage, and treatment.

Results

According to the LASSO-Cox regression results, the number of nodules, lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), alkaline phosphatase (ALP), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (SLR) and C-reactive protein (CRP) were included for prognostic model construction. The C-index of the prognostic model was 0.759 (95% CI 0.723–0.797) in the development cohort and 0.796 (95% CI 0.737–0.855) in the validation cohort, and its predictive ability was better than TNM stage and treatment. The TD-ROC showed similar results. K–M survival analysis showed that NV-HCC patients with low risk scores had a better prognosis (P < 0.05). A nomogram based on the prognostic model, TNM stage, and treatment was constructed with sufficient discriminatory power with C-indexes of 0.78 and 0.85 in the development and validation cohort, respectively.

Conclusion

For NV-HCC, this prognostic model could predict an OS benefit for patients, which may assist clinicians in designing individualized therapeutic strategies.
Literature
1.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. 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.PubMedCrossRef
2.
Amini M, Looha MA, Zarean E, Pourhoseingholi MA. Global pattern of trends in incidence, mortality, and mortality-to-incidence ratio rates related to liver cancer, 1990–2019: a longitudinal analysis based on the global burden of disease study. BMC Public Health. 2022;22(1):604.PubMedPubMedCentralCrossRef
3.
Perisetti A, Goyal H, Yendala R, Thandassery RB, Giorgakis E. Non-cirrhotic hepatocellular carcinoma in chronic viral hepatitis: current insights and advancements. World J Gastroenterol. 2021;27(24):3466–82.PubMedPubMedCentralCrossRef
4.
Bosch FX, Ribes J, Borras J. Epidemiology of primary liver cancer. Semin Liver Dis. 1999;19(3):271–85.PubMedCrossRef
5.
Wallace MC, Preen D, Jeffrey GP, Adams LA. The evolving epidemiology of hepatocellular carcinoma: a global perspective. Expert Rev Gastroenterol Hepatol. 2015;9(6):765–79.PubMedCrossRef
6.
7.
Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH, Group R-HS. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295(1):65–73.PubMedCrossRef
8.
Qu LS, Jin F, Huang XW, Shen XZ. High hepatitis B viral load predicts recurrence of small hepatocellular carcinoma after curative resection. J Gastrointest Surg. 2010;14(7):1111–20.PubMedCrossRef
9.
Sohn W, Paik YH, Kim JM, Kwon CH, Joh JW, Cho JY, Gwak GY, Choi MS, Lee JH, Koh KC, et al. HBV DNA and HBsAg levels as risk predictors of early and late recurrence after curative resection of HBV-related hepatocellular carcinoma. Ann Surg Oncol. 2014;21(7):2429–35.PubMedCrossRef
10.
Kadalayil L, Benini R, Pallan L, O’Beirne J, Marelli L, Yu D, Hackshaw A, Fox R, Johnson P, Burroughs AK, et al. A simple prognostic scoring system for patients receiving transarterial embolisation for hepatocellular cancer. Ann Oncol. 2013;24(10):2565–70.PubMedPubMedCentralCrossRef
11.
Chon YE, Park H, Hyun HK, Ha Y, Kim MN, Kim BK, Lee JH, Kim SU, Kim DY, Ahn SH, et al. Development of a new nomogram including neutrophil-to-lymphocyte ratio to predict survival in patients with hepatocellular carcinoma undergoing transarterial chemoembolization. Cancers. 2019;11(4):509.PubMedCentralCrossRef
12.
Goto T, Yoshida H, Tateishi R, Enooku K, Goto E, Sato T, Ohki T, Masuzaki R, Imamura J, Shiina S, et al. Influence of serum HBV DNA load on recurrence of hepatocellular carcinoma after treatment with percutaneous radiofrequency ablation. Hepatol Int. 2011;5(3):767–73.PubMedCrossRef
13.
Bruix J, Cheng AL, Meinhardt G, Nakajima K, De Sanctis Y, Llovet J. Prognostic factors and predictors of sorafenib benefit in patients with hepatocellular carcinoma: analysis of two phase III studies. J Hepatol. 2017;67(5):999–1008.PubMedCrossRef
14.
Harimoto N, Shirabe K, Nakagawara H, Toshima T, Yamashita Y, Ikegami T, Yoshizumi T, Soejima Y, Ikeda T, Maehara Y. Prognostic factors affecting survival at recurrence of hepatocellular carcinoma after living-donor liver transplantation: with special reference to neutrophil/lymphocyte ratio. Transplantation. 2013;96(11):1008–12.PubMedCrossRef
15.
Huang J, Liu FC, Li L, Zhou WP, Jiang BG, Pan ZY. Nomograms to predict the long-time prognosis in patients with alpha-fetoprotein negative hepatocellular carcinoma following radical resection. Cancer Med. 2020;9(8):2791–802.PubMedPubMedCentralCrossRef
16.
Pinero F, Marciano S, Anders M, Orozco Ganem F, Zerega A, Cagliani J, Andriani O, de Santibanes E, Gil O, Podesta LG, et al. Identifying patients at higher risk of hepatocellular carcinoma recurrence after liver transplantation in a multicenter cohort study from Argentina. Eur J Gastroenterol Hepatol. 2016;28(4):421–7.PubMedCrossRef
17.
Witjes CD, IJzermans JN, van der Eijk AA, Hansen BE, Verhoef C, de Man RA. Quantitative HBV DNA and AST are strong predictors for survival after HCC detection in chronic HBV patients. Neth J Med. 2011;69(11):508–13.PubMed
18.
Lai Q, Castro Santa E, Rico Juri JM, Pinheiro RS, Lerut J. Neutrophil and platelet-to-lymphocyte ratio as new predictors of dropout and recurrence after liver transplantation for hepatocellular cancer. Transplant Int. 2014;27(1):32–41.CrossRef
19.
Zhang M, Bi LF, Fang JH, Su XL, Da GL, Kuwamori T, Kagamimori S. Beneficial effects of taurine on serum lipids in overweight or obese non-diabetic subjects. Amino Acids. 2004;26(3):267–71.PubMedCrossRef
20.
Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol. 2019;16(10):589–604.PubMedPubMedCentralCrossRef
21.
Omata M, Cheng AL, Kokudo N, Kudo M, Lee JM, Jia J, Tateishi R, Han KH, Chawla YK, Shiina S, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hep Intl. 2017;11(4):317–70.CrossRef
22.
Chang MH, You SL, Chen CJ, Liu CJ, Lee CM, Lin SM, Chu HC, Wu TC, Yang SS, Kuo HS, et al. Decreased incidence of hepatocellular carcinoma in hepatitis B vaccinees: a 20-year follow-up study. J Natl Cancer Inst. 2009;101(19):1348–55.PubMedCrossRef
23.
Birim O, Kappetein AP, Waleboer M, Puvimanasinghe JP, Eijkemans MJ, Steyerberg EW, Versteegh MI, Bogers AJ. Long-term survival after non-small cell lung cancer surgery: development and validation of a prognostic model with a preoperative and postoperative mode. J Thorac Cardiovasc Surg. 2006;132(3):491–8.PubMedCrossRef
24.
Yau T, Tang VY, Yao TJ, Fan ST, Lo CM, Poon RT. Development of Hong Kong Liver Cancer staging system with treatment stratification for patients with hepatocellular carcinoma. Gastroenterology. 2014;146(7):1691.e1693-1700.CrossRef
25.
Liu MZ, Tang LL, Zong JF, Huang Y, Sun Y, Mao YP, Liu LZ, Lin AH, Ma J. Evaluation of sixth edition of AJCC staging system for nasopharyngeal carcinoma and proposed improvement. Int J Radiat Oncol Biol Phys. 2008;70(4):1115–23.PubMedCrossRef
26.
Tibshirani R. The lasso method for variable selection in the Cox model. Stat Med. 1997;16(4):385–95.PubMedCrossRef
27.
Mazzotta AD, Pascale A, Cano L, Rosmorduc O, Allard MA, Sa Cunha A, Adam R, Cherqui D, Vibert E, Golse N. Number of hepatocellular carcinoma nodules in patients listed for liver transplantation within alpha-fetoprotein score: a new prognostic risk factor. Transpl Int. 2021;34(5):954–63.PubMedCrossRef
28.
Singh J, Shukla D, Gupta S, Shrivastav BR, Tiwari PK. Clinical epidemiology of gallbladder cancer in North-Central India and association of immunological markers, NLR, MLR and PLR in the diagnostic/prognostic prediction of GBC. Cancer Treat Res Commun. 2021;28:100431.PubMedCrossRef
29.
Wang J, Li H, Xu R, Lu T, Zhao J, Zhang P, Qu L, Zhang S, Guo J, Zhang L. The MLR, NLR, PLR and D-dimer are associated with clinical outcome in lung cancer patients treated with surgery. BMC Pulm Med. 2022;22(1):104.PubMedPubMedCentralCrossRef
30.
Zhang Z, Lin Q, Chen Y, Su C, Lin W, Wei D, Zhang L, Liu H. Prognostic evaluation of metastasis-related lymphocyte/monocyte ratio in stage—breast cancer receiving chemotherapy. Front Oncol. 2021;11:782383.PubMedCrossRef
31.
Kuang DM, Peng C, Zhao Q, Wu Y, Chen MS, Zheng L. Activated monocytes in peritumoral stroma of hepatocellular carcinoma promote expansion of memory T helper 17 cells. Hepatology. 2010;51(1):154–64.PubMedCrossRef
32.
Drotman RB, Lawhorn GT. Serum enzymes as indicators of chemically induced liver damage. Drug Chem Toxicol. 1978;1(2):163–71.PubMedCrossRef
33.
Wei XL, Zhang DS, He MM, Jin Y, Wang DS, Zhou YX, Bai L, Li ZZ, Luo HY, Wang FH, et al. The predictive value of alkaline phosphatase and lactate dehydrogenase for overall survival in patients with esophageal squamous cell carcinoma. Tumour Biol. 2016;37(2):1879–87.PubMedCrossRef
34.
Ji F, Fu SJ, Guo ZY, Pang H, Ju WQ, Wang DP, Hua YP, He XS. Prognostic value of combined preoperative lactate dehydrogenase and alkaline phosphatase levels in patients with resectable pancreatic ductal adenocarcinoma. Medicine. 2016;95(27):e4065.PubMedPubMedCentralCrossRef
35.
Kim SY, Yoon MJ, Park YI, Kim MJ, Nam BH, Park SR. Nomograms predicting survival of patients with unresectable or metastatic gastric cancer who receive combination cytotoxic chemotherapy as first-line treatment. Gastric Cancer. 2018;21(3):453–63.PubMedCrossRef
36.
Xu XS, Wan Y, Song SD, Chen W, Miao RC, Zhou YY, Zhang LQ, Qu K, Liu SN, Zhang YL, et al. Model based on gamma-glutamyltransferase and alkaline phosphatase for hepatocellular carcinoma prognosis. World J Gastroenterol. 2014;20(31):10944–52.PubMedPubMedCentralCrossRef
37.
Chen SL, Li JP, Li LF, Zeng T, He X. Elevated preoperative serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio is associated with better prognosis in patients undergoing curative treatment for gastric adenocarcinoma. Int J Mol Sci. 2016;17(6):911.PubMedCentralCrossRef
38.
Li L, Zeng Q, Xue N, Wu M, Liang Y, Xu Q, Feng L, Xing S, Chen S. A nomogram based on aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio to predict prognosis after surgery in gastric cancer patients. Cancer Control. 2020;27(1):1073274820954458.PubMedPubMedCentralCrossRef
39.
40.
Tokunaga R, Sakamoto Y, Nakagawa S, Miyamoto Y, Yoshida N, Oki E, Watanabe M, Baba H. Prognostic nutritional index predicts severe complications, recurrence, and poor prognosis in patients with colorectal cancer undergoing primary tumor resection. Dis Colon Rectum. 2015;58(11):1048–57.PubMedCrossRef
41.
Mohri T, Mohri Y, Shigemori T, Takeuchi K, Itoh Y, Kato T. Impact of prognostic nutritional index on long-term outcomes in patients with breast cancer. World J Surg Oncol. 2016;14(1):170.PubMedPubMedCentralCrossRef
42.
Kanda M, Fujii T, Kodera Y, Nagai S, Takeda S, Nakao A. Nutritional predictors of postoperative outcome in pancreatic cancer. Br J Surg. 2011;98(2):268–74.PubMedCrossRef
Metadata
Title
Establishment and validation of a novel prognostic model for non-virus-related hepatocellular carcinoma
Authors
Yu Jiang
Shulin Chen
Yaxian Wu
Yuanye Qu
Lina Jia
Qingxia Xu
Shuqin Dai
Ning Xue
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2022
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-022-02725-5

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