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在胰腺癌中,通过预测总生存期的致癌基因和肿瘤抑制基因的突变特征:贝叶斯网络荟萃分析。

The Mutation Portraits of Oncogenes and Tumor Supressor Genes in Predicting the Overall Survival in Pancreatic Cancer: A Bayesian Network Meta-Analysis.

机构信息

Digestive Surgery Training Program, Department of Surgery, Hasanuddin University, Dr. Wahidin Sudirohusodo General Hospital, Makassar, Sulawesi Selatan, Indonesia.

Division of Digestive Surgery, Department of Surgery, Hasanuddin University, Dr. Wahidin Sudirohusodo General Hospital, Makassar, Sulawesi Selatan, Indonesia.

出版信息

Asian Pac J Cancer Prev. 2023 Aug 1;24(8):2895-2902. doi: 10.31557/APJCP.2023.24.8.2895.

Abstract

INTRODUCTION

In pancreatic cancer, the carcinogenesis can not be separated from genetics mutations. The portraits of genes alterations majorily including oncogenes (KRAS, HER2, PD-L1) and tumor supressor genes (P53, CDKN2A, SMAD4). Besides being notorious a screening marker, the genetic mutations were related to the prognosis of pancreatic cancer. The aim of this study is to determine the genetic mutations portrait in predicting the overall survival in pancreatic cancer.

METHODS

The network meta analysis (NMA) was registered in PROSPERO (CRD42023397976) and conducted in accordance with the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) in addition of NMA extension guidance. Comprehensive searches were done including all studies which reported the overall survival of pancreatic cancer subjects with KRAS, HER2, PD-L1, P53, CDKN2A, SMAD4. Data were collected and analysis will be done based on Bayesian method, Markov Chain Monte Carlo algorithm, using BUGSnet package in R studio. Transivity was controlled by methods and consistency of the NMA will be fitted by deviance information criterion. Data analysis in NMA were presented in Sucra plot, league table, and forest plot.

RESULTS

Twenty-four studies were included in this NMA with 4613 total subjects. The NMA was conducted in random-effects, consistent, and convergence model. Relative to control, the genetic mutation of SMAD4 (HR 1.84; 95%CI 1.39-2.46), HER2 (HR 1.76; 95%CI 1.14-2.71), and KRAS (HR 1.7; 95%CI 1.19-2.48) were significant to have worse survival. The mutations of PD-L1, P53, and CDKN2A also showed poor survival, but not statistically significant compared to control.

CONCLUSION

In pancreatic cancer, the mutation of SMAD4 predicted the worst overall survival, compared to control, also mutation of HER2, KRAS, PD-L1, P53, and CDKN2A.

摘要

简介

在胰腺癌中,癌变过程与基因突变密不可分。主要的基因改变特征包括癌基因(KRAS、HER2、PD-L1)和肿瘤抑制基因(P53、CDKN2A、SMAD4)。除了作为著名的筛查标志物外,基因突变还与胰腺癌的预后相关。本研究旨在确定基因突变为预测胰腺癌总生存期的特征。

方法

网络荟萃分析(NMA)在 PROSPERO(CRD42023397976)中进行注册,并按照 PRISMA-P(系统评价和荟萃分析报告的首选项目)以及 NMA 扩展指南进行。全面检索了所有报告胰腺癌患者 KRAS、HER2、PD-L1、P53、CDKN2A、SMAD4 总生存期的研究。收集数据并基于贝叶斯方法、马尔可夫链蒙特卡罗算法进行分析,使用 R 工作室中的 BUGSnet 包进行分析。通过方法控制transitivity,通过偏差信息准则拟合 NMA 的一致性。NMA 中的数据分析以 Sucra 图、联赛表和森林图呈现。

结果

本 NMA 纳入了 24 项研究,共计 4613 例患者。NMA 采用随机效应、一致和收敛模型进行分析。与对照组相比,SMAD4(HR 1.84;95%CI 1.39-2.46)、HER2(HR 1.76;95%CI 1.14-2.71)和 KRAS(HR 1.7;95%CI 1.19-2.48)的基因突变与较差的生存显著相关。PD-L1、P53 和 CDKN2A 的突变也表现出较差的生存,但与对照组相比无统计学意义。

结论

在胰腺癌中,与对照组相比,SMAD4 突变预测总生存最差,HER2、KRAS、PD-L1、P53 和 CDKN2A 突变也是如此。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c879/10685232/f7e066c89edc/APJCP-24-2895-g001.jpg

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