Research Paper Volume 12, Issue 2 pp 1828—1842

Autophagy-related gene P4HB: a novel diagnosis and prognosis marker for kidney renal clear cell carcinoma

Longxiang Xie 1, *, , Huimin Li 1, *, , Lu Zhang 1, *, , Xiaoyu Ma 1, , Yifang Dang 1, , Jinshuai Guo 1, , Jiahao Liu 1, , Linna Ge 1, , Fangmei Nan 1, , Huan Dong 1, , Zhongyi Yan 1, , Xiangqian Guo 1, ,

  • 1 Department of Predictive Medicine, Institute of Biomedical Informatics, Cell Signal Transduction Laboratory, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Henan University, Kaifeng 475004, China
* Co-first authors

received: September 1, 2019 ; accepted: January 2, 2020 ; published: January 30, 2020 ;

https://doi.org/10.18632/aging.102715
How to Cite

Copyright © 2020 Xie et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Autophagy can protect cells and organisms from stressors such as nutrient deprivation, and is involved in many pathological processes including human cancer. Therefore, it is necessary to investigate the role of autophagy-related genes (ARGs) in cancer. In this study, we investigated the gene expression of 222 ARGs in 1048 Kidney Renal Clear Cell Carcinoma (KIRC) cases, from 5 independent cohorts. The gene expression of ARGs were first evaluated in the The Cancer Genome Atlas (TCGA) by Recevier Operating Characteristic (ROC) analysis to select potential biomarkers with extremely high ability in KIRC detection (AUC≥0.85 and p<0.0001). Then in silico procedure progressively leads to the selection of two genes in a three rounds of validation performed in four human KIRC-patients datasets including two independent Gene Expression Omnibus (GEO) datasets, Oncomine dataset and Human Protein Atlas dataset. Finally, only P4HB (Prolyl 4-hydroxylase, beta polypeptide) gene was experimentally validated by RT-PCR between control kidney cells and cancer cells. Following univariate and multivariate analyses of TCGA-KIRC clinical data showed that P4HB expression is an independent prognostic indicator of unfavorable overall survival (OS) for KIRC patients. Based on these findings, we proposed that P4HB might be one potential novel KIRC diagnostic and prognostic biomarker at both mRNA and protein levels.

Abbreviations

ARGs: Autophagy-related genes; TCGA: The Cancer Genome Atlas; GEO: Gene Expression Omnibus; HPA: Human Protein Atlas; KIRC: Kidney Renal Clear Cell Carcinoma; P4HB: Prolyl 4-hydroxylase; beta polypeptide; PPI: Protein-protein interactions; EMT: Epithelial to mesenchymal transition; GABAR: GABA type A receptor associated protein like 1; AUC: Area under the curve; ROC: Receiver operating characteristic; ER: Endoplasmic reticulum; OS: Over-all survival; CALR: calreticulin; HSP90B1: heat shock protein 90kDa beta member 1; HSPA5: heat shock protein family A member 5; PPIB: peptidylprolyl isomerase B; MTTP: microsomal triglyceride transfer protein; P4HA3: prolyl 4-hydroxylase subunit alpha 3; PDIA6: protein disulfide isomerase family A member 6; PRKCSH: protein kinase C substrate 80K-H; CALU: calumenin.