Predicted Prognosis of Patients with Pancreatic Cancer by Machine Learning

Abstract

Purpose: Pancreatic cancer remains a disease of high mortality despite advanced diagnostic techniques. Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in pancreatic cancers. MUC1 and MUC4 expression are related to the aggressive behavior of human neoplasms and a poor patient outcome. In contrast, MUC2 is a tumor suppressor, and we have previously reported that MUC2 is a favorable prognostic factor in pancreatic neoplasia. This study investigates whether the methylation status of three mucin genes from postoperative tissue specimens from patients with pancreatic neoplasms could serve as a predictive biomarker for outcome after surgery.Experimental Design: We evaluated the methylation status of MUC1, MUC2, and MUC4 promoter regions in pancreatic tissue samples from 191 patients with various pancreatic lesions using methylation-specific electrophoresis. Then, integrating these results and clinicopathologic features, we used support vector machine-, neural network-, and multinomial-based methods to develop a prognostic classifier.Results: Significant differences were identified between the positive-and negative-prediction classifiers of patients in 5-year overall survival (OS) in the cross-validation test. Multivariate analysis revealed that these prognostic classifiers were independent prognostic factors analyzed by not only neoplastic tissues but also nonneoplastic tissues. These classifiers had higher predictive accuracy for OS than tumor size, lymph node metastasis, distant metastasis, and age and can complement the prognostic value of the TNM staging system.Conclusions: Analysis of epigenetic changes in mucin genes may be of diagnostic utility and one of the prognostic predictors for patients with pancreatic ductal adenocarcinoma.

Prognostic value of Glypican family genes in early-stage pancreatic ductal adenocarcinoma after pancreaticoduodenectomy and possible mechanisms

“…In pancreatic cancer, the transcription factor hif- 2α can speed up metabolism and promote tumor proliferation and high level of hif- 2α correlates with worse OS [ 61 , 62 ]. The methylation status of GRAP2 , ICAM3 , A2ML1 , MUC1, and MUC4 can influence the expression of these genes, which is associated with survival of pancreatic cancer [ 63 , 64 ]. Phosphatidylserine is related to apoptosis of pancreatic cancer cells with the involvement of microparticles [ 65 ].…”

Expression signature, prognosis value, and immune characteristics of MUC1 identified by pan-cancer analysis

“…This study also revealed that the expression of several DNA methylation/demethylation factors have a signi cant correlation with MUC1 methylation status. Subsequent studies also concluded that aberrant methylation of MUC1 promoters are potential prognostic biomarkers for pancreatic ductal adenocarcinomas [49]. DNA methylation refers to the chemical modi cation that transfers methyl to speci c bases in the DNA chain under the action of DNA methylase.…”

Prognostic value of Glypican family genes in early-stage pancreatic ductal adenocarcinoma after pancreaticoduodenectomy and possible mechanisms

“…For pancreatic cancer, the transcription factor, hif-2α, can speed up metabolism and promote tumor proliferation and high level of hif-2α correlates with worse patients OS (61,62). Methylation status of GRAP2, ICAM3, A2ML1, MUC1 and MUC4 can in uence expression of these genes, which is associated with survival of pancreatic cancer (63,64). Phosphatidylserine is related to the apoptosis of pancreatic cancer cells with the intervention of microparticles (65).…”