In silico development and clinical validation of novel 8 gene signature based on lipid metabolism related genes in colon adenocarcinoma

作者: Lei Gu , Chunhui Jiang , Chunjie Xu , Ye Liu , Siyuan Wen

DOI: 10.1016/J.PHRS.2021.105644

关键词:

摘要: Abstract Background Changes in lipid metabolism pathways play a major role colon carcinogenesis and development. Hence, we conducted systematic analysis of metabolism-related genes to explore new markers that predict the prognosis adenocarcinoma (COAD). Methods The non-negative Matrix Factorization (NMF) algorithm was applied identify molecular subtypes based on genes. A weighted correlation network (WCGNA) used co-expressed genes, Lasso multivariate Cox performed build risk model. timer database analyze immune infiltration gene signature GSCALite for genome-wide signature. Results TCGA-COAD samples were divided into 3 2739 identified by WGCNA analysis. Finally, an 8-gene (RTN2, FYN, HEYL, FAM69A, FBXL5, HMGN2, LGALS4, STOX1) constructed demonstrated good robustness different datasets, as well independent factor cancer patients’ prognosis. In addition, our model’s predictive efficacy overall higher than other published models, 8 genes’ expression indicated RTN2, STOX1 all expressed highly significantly COAD, while FYN HMGN2 poorly tissues, which confirmed immunohistochemistry. differently COAD correlated with clinical variables. Genome-wide revealed mutation frequency highest, genome methylation influenced significantly; further, HEYL FBXL5 positively Copy number variation (CNV) regulated CNV most cancers. austocystin d bafilomycin played important anti-tumor immunotherapy. RTN2 associated EMT pathway’s activation, LGALS4 inhibition. Conclusion This study novel marker survival.

参考文章(62)
Dingzhi Wang, Lingchen Fu, Haiyan Sun, Lixia Guo, Raymond N. DuBois, Prostaglandin E2 Promotes Colorectal Cancer Stem Cell Expansion and Metastasis in Mice Gastroenterology. ,vol. 149, pp. 1884- 1895 ,(2015) , 10.1053/J.GASTRO.2015.07.064
Weidong Wu, Honghua Ding, Jun Cao, Weihao Zhang, None, FBXL5 Inhibits Metastasis of Gastric Cancer Through Suppressing Snail1 Cellular Physiology and Biochemistry. ,vol. 35, pp. 1764- 1772 ,(2015) , 10.1159/000373988
Yoshihito D. Saito, Ana R. Jensen, Ravi Salgia, Edwin M. Posadas, Fyn: a novel molecular target in cancer. Cancer. ,vol. 116, pp. 1629- 1637 ,(2010) , 10.1002/CNCR.24879
Subhra K. Biswas, Metabolic Reprogramming of Immune Cells in Cancer Progression. Immunity. ,vol. 43, pp. 435- 449 ,(2015) , 10.1016/J.IMMUNI.2015.09.001
Daniel Elias, Henrik J. Ditzel, Fyn is an important molecule in cancer pathogenesis and drug resistance. Pharmacological Research. ,vol. 100, pp. 250- 254 ,(2015) , 10.1016/J.PHRS.2015.08.010
Kung-Kai Kuo, Shu-Fang Jian, Yi-Jin Li, Shi-Wei Wan, Ching-Chieh Weng, KuanTe Fang, Deng-Chyang Wu, Kuang-Hung Cheng, Epigenetic inactivation of transforming growth factor-β1 target gene HEYL, a novel tumor suppressor, is involved in the P53-induced apoptotic pathway in hepatocellular carcinoma Hepatology Research. ,vol. 45, pp. 782- 793 ,(2015) , 10.1111/HEPR.12414
Peter Langfelder, Steve Horvath, WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. ,vol. 9, pp. 559- 559 ,(2008) , 10.1186/1471-2105-9-559
Marie van Dijk, Sascha Drewlo, Cees B.M. Oudejans, Differential methylation of STOX1 in human placenta. Epigenetics. ,vol. 5, pp. 736- 742 ,(2010) , 10.4161/EPI.5.8.13084
GUOJUN LIANG, ENJIE XU, CHAOQUN YANG, CHENGLIN ZHANG, XIAOLONG SHENG, XUHUI ZHOU, Nucleosome-binding protein HMGN2 exhibits antitumor activity in human SaO2 and U2-OS osteosarcoma cell lines. Oncology Reports. ,vol. 33, pp. 1300- 1306 ,(2015) , 10.3892/OR.2014.3689
PEIYING YANG, CARRIE A. CARTWRIGHT, JIN LI, SIJIN WEN, INA N. PROKHOROVA, IMAD SHUREIQI, PATRICIA TRONCOSO, NORA M. NAVONE, ROBERT A. NEWMAN, JERI KIM, Arachidonic acid metabolism in human prostate cancer International Journal of Oncology. ,vol. 41, pp. 1495- 1503 ,(2012) , 10.3892/IJO.2012.1588