Construction of overall survival model for gastric cancer based on clinical characteristics and genomics_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

HU Renwang ,  GONG Jianping

Department of Gastrointestinal Surgery, Tongji Hospital, Tongji Medical College in Huazhong University of Science and Technology, Wuhan 430030, P. R. China;

Corresponding author：

GONG Jianping, Email: jpgong@tjh.tjmu.edu.cn

Keywords：

gastric cancer; predictive model; overall survival rate

DOI：

10.7507/1007-9424.202007053

Video：

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Objective To construct a new model for predicting the overall survival rate of gastric cancer and to guide the clinical work.Methods The clinical information and gene expression information of patients with gastric cancer were downloaded through The Cancer Genome Atlas (TCGA) database. The clinicopathologic characteristics and gene expression information affecting the overall survival rate of gastric cancer patients were screened by univariate COX regression and Lasson regression, then the predictive model was constructed by multiple COX regression model, and the predictive model was tested by receiver operating characteristic curve, calibration curve and decision curve analysis curve. The effect of genes included in the predictive model on the overall survival rate of patients with gastric cancer was discussed, and the predictive model diagram was drawn.Results Through repeated screening and comparison of the model, the patient’s age, T stage, N stage, M stage and 12 genes (INCENP, IGHD3-16, ITFG1-AS1, NEK5, MATN3, YWHABP2, SYT12, LINC01210, ZNF385C, LINC01980, CYMP-AS1 and FAT3) were included in the predictive model. The prediction ability of this model was close to or more than 80%, which was significantly higher than that of the traditional TNM staging prediction system. All the indexes included in the model were significantly different by univariate and multivariate COX regression analysis（P<0.05）, and the 12 genes included were the risk factors affecting the overall survival rate of gastric cancer.Conclusion The gastric cancer prediction model constructed by combining clinical characteristics and genomics has good predictive ability and can guide clinical work.

Citation： HU Renwang, GONG Jianping. Construction of overall survival model for gastric cancer based on clinical characteristics and genomics. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(4): 465-471. doi: 10.7507/1007-9424.202007053 Copy

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4.	Liu J, Lichtenberg T, Hoadley KA, et al. An integrated TCGA pan-cancer clinical data resource to drive high-quality survival outcome analytics. Cell, 2018, 173(2): 400-416.
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9.	Petrovchich I, Ford JM. Genetic predisposition to gastric cancer. Semin Oncol, 2016, 43(5): 554-559.
10.	Gu Y, Chen T, Li G, et al. LncRNAs: emerging biomarkers in gastric cancer. Future Oncol, 2015, 11(17): 2427-2441.
11.	Sun M, Nie FQ, Wang ZX, et al. Involvement of lncRNA dysregulation in gastric cancer. Histol Histopathol, 2016, 31(1): 33-39.
12.	Khorkova O, Hsiao J, Wahlestedt C. Basic biology and therapeutic implications of lncRNA. Adv Drug Deliv Rev, 2015, 87: 15-24.
13.	Peng WX, Koirala P, Mo YY. LncRNA-mediated regulation of cell signaling in cancer. Oncogene, 2017, 36(41): 5661-5667.
14.	Ma Y, Zhang J, Wen L, et al. Membrane-lipid associated lncRNA: A new regulator in cancer signaling. Cancer Lett, 2018, 419: 27-29.
15.	Lv X, Zhao Y, Zhang L, et al. Development of a novel gene signature in patients without Helicobacter pylori infection gastric cancer. J Cell Biochem, 2020, 121(2): 1842-1854.
16.	Zhao L, Jiang L, He L, et al. Identification of a novel cell cycle-related gene signature predicting survival in patients with gastric cancer. J Cell Physiol, 2019, 234(5): 6350-6360.
17.	Prosser SL, Sahota NK, Pelletier L, et al. Nek5 promotes centrosome integrity in interphase and loss of centrosome cohesion in mitosis. J Cell Biol, 2015, 209(3): 339-348.
18.	Pei J, Zhang J, Yang X, et al. NEK5 promotes breast cancer cell proliferation through up-regulation of Cyclin A2. Mol Carcinog, 2019, 58(6): 933-943.
19.	Melo-Hanchuk TD, Martins MB, Cunha LL, et al. Expression of the NEK family in normal and cancer tissue: an immuno-histochemical study. BMC Cancer, 2020, 20(1): 23.
20.	Zhang C, Liang Y, Ma MH, et al. KRT15, INHBA, MATN3, and AGT are aberrantly methylated and differentially expressed in gastric cancer and associated with prognosis. Pathol Res Pract, 2019, 215(5): 893-899.
21.	Wu PL, He YF, Yao HH, et al. Martrilin-3 (MATN3) overexpression in gastric adenocarcinoma and its prognostic significance. Med Sci Monit, 2018, 24: 348-355.
22.	Liu K, Luo J, Shao C, et al. Synaptotagmin 12 (SYT12) gene expression promotes cell proliferation and progression of lung adenocarcinoma and involves the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway. Med Sci Monit, 2020, 26: e920351.
23.	Eizuka K, Nakashima D, Oka N, et al. SYT12 plays a critical role in oral cancer and may be a novel therapeutic target. J Cancer, 2019, 10(20): 4913-4920.
24.	Ojasalu K, Brehm C, Hartung K, et al. Upregulation of mesothelial genes in ovarian carcinoma cells is associated with an unfavorable clinical outcome and the promotion of cancer cell adhesion. Mol Oncol, 2020, 14(9): 2142-2162.
25.	Katoh M. Function and cancer genomics of FAT family genes (review). Int J Oncol, 2012, 41(6): 1913-1918.
26.	Zhang C, Liu J, Zhang Y, et al. LINC01210 accelerates proliferation, invasion and migration in ovarian cancer through epigenetically downregulating KLF4. Biomed Pharmacother, 2019, 119: 109431.
27.	Zhang S, Liang Y, Wu Y, et al. Upregulation of a novel lncRNA LINC01980 promotes tumor growth of esophageal squamous cell carcinoma. Biochem Biophys Res Commun, 2019, 513(1): 73-80.
28.	Liang X, Wu Z, Shen S, et al. LINC01980 facilitates esophageal squamous cell carcinoma progression via regulation of miR-190a-5p/MYO5A pathway. Arch Biochem Biophys, 2020, 686: 108371.

1. Wagner AD, Syn NL, Moehler M, et al. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev, 2017, 8(8): CD004064.
2. Wittekind C. The development of the TNM classification of gastric cancer. Pathol Int, 2015, 65(8): 399-403.
3. Lin JX, Lin JP, Xie JW, et al. Is the AJCC TNM staging system still appropriate for gastric cancer patients survival after 5 years? Eur J Surg Oncol, 2019, 45(6): 1115-1120.
4. Liu J, Lichtenberg T, Hoadley KA, et al. An integrated TCGA pan-cancer clinical data resource to drive high-quality survival outcome analytics. Cell, 2018, 173(2): 400-416.
5. Rousson V, Zumbrunn T. Decision curve analysis revisited: overall net benefit, relationships to ROC curve analysis, and application to case-control studies. BMC Med Inform Decis Mak, 2011, 11: 45.
6. Kerr KF, Brown MD, Zhu K, et al. Assessing the clinical impact of risk prediction models with decision curves: guidance for correct interpretation and appropriate use. J Clin Oncol, 2016, 34(21): 2534-2540.
7. Strong VE. Progress in gastric cancer. Updates Surg, 2018, 70(2): 157-159.
8. Elimova E, Wadhwa R, Shiozaki H, et al. Molecular biomarkers in gastric cancer. J Natl Compr Canc Netw, 2015, 13(4): e19-e29.
9. Petrovchich I, Ford JM. Genetic predisposition to gastric cancer. Semin Oncol, 2016, 43(5): 554-559.
10. Gu Y, Chen T, Li G, et al. LncRNAs: emerging biomarkers in gastric cancer. Future Oncol, 2015, 11(17): 2427-2441.
11. Sun M, Nie FQ, Wang ZX, et al. Involvement of lncRNA dysregulation in gastric cancer. Histol Histopathol, 2016, 31(1): 33-39.
12. Khorkova O, Hsiao J, Wahlestedt C. Basic biology and therapeutic implications of lncRNA. Adv Drug Deliv Rev, 2015, 87: 15-24.
13. Peng WX, Koirala P, Mo YY. LncRNA-mediated regulation of cell signaling in cancer. Oncogene, 2017, 36(41): 5661-5667.
14. Ma Y, Zhang J, Wen L, et al. Membrane-lipid associated lncRNA: A new regulator in cancer signaling. Cancer Lett, 2018, 419: 27-29.
15. Lv X, Zhao Y, Zhang L, et al. Development of a novel gene signature in patients without Helicobacter pylori infection gastric cancer. J Cell Biochem, 2020, 121(2): 1842-1854.
16. Zhao L, Jiang L, He L, et al. Identification of a novel cell cycle-related gene signature predicting survival in patients with gastric cancer. J Cell Physiol, 2019, 234(5): 6350-6360.
17. Prosser SL, Sahota NK, Pelletier L, et al. Nek5 promotes centrosome integrity in interphase and loss of centrosome cohesion in mitosis. J Cell Biol, 2015, 209(3): 339-348.
18. Pei J, Zhang J, Yang X, et al. NEK5 promotes breast cancer cell proliferation through up-regulation of Cyclin A2. Mol Carcinog, 2019, 58(6): 933-943.
19. Melo-Hanchuk TD, Martins MB, Cunha LL, et al. Expression of the NEK family in normal and cancer tissue: an immuno-histochemical study. BMC Cancer, 2020, 20(1): 23.
20. Zhang C, Liang Y, Ma MH, et al. KRT15, INHBA, MATN3, and AGT are aberrantly methylated and differentially expressed in gastric cancer and associated with prognosis. Pathol Res Pract, 2019, 215(5): 893-899.
21. Wu PL, He YF, Yao HH, et al. Martrilin-3 (MATN3) overexpression in gastric adenocarcinoma and its prognostic significance. Med Sci Monit, 2018, 24: 348-355.
22. Liu K, Luo J, Shao C, et al. Synaptotagmin 12 (SYT12) gene expression promotes cell proliferation and progression of lung adenocarcinoma and involves the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway. Med Sci Monit, 2020, 26: e920351.
23. Eizuka K, Nakashima D, Oka N, et al. SYT12 plays a critical role in oral cancer and may be a novel therapeutic target. J Cancer, 2019, 10(20): 4913-4920.
24. Ojasalu K, Brehm C, Hartung K, et al. Upregulation of mesothelial genes in ovarian carcinoma cells is associated with an unfavorable clinical outcome and the promotion of cancer cell adhesion. Mol Oncol, 2020, 14(9): 2142-2162.
25. Katoh M. Function and cancer genomics of FAT family genes (review). Int J Oncol, 2012, 41(6): 1913-1918.
26. Zhang C, Liu J, Zhang Y, et al. LINC01210 accelerates proliferation, invasion and migration in ovarian cancer through epigenetically downregulating KLF4. Biomed Pharmacother, 2019, 119: 109431.
27. Zhang S, Liang Y, Wu Y, et al. Upregulation of a novel lncRNA LINC01980 promotes tumor growth of esophageal squamous cell carcinoma. Biochem Biophys Res Commun, 2019, 513(1): 73-80.
28. Liang X, Wu Z, Shen S, et al. LINC01980 facilitates esophageal squamous cell carcinoma progression via regulation of miR-190a-5p/MYO5A pathway. Arch Biochem Biophys, 2020, 686: 108371.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Construction of overall survival model for gastric cancer based on clinical characteristics and genomics

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