Prediction of Prognostic Biomarkers and Construction of an Autophagy Prognostic Model for Colorectal Cancer Using Bioinformatics

Overview

Journal Technol Cancer Res Treat

Specialties Biomedical Engineering
Oncology
Pharmacology

Date 2020 Dec 28

PMID 33357130

Citations 7

Authors

Ting-Ting Liu

Shu-Min Liu

Affiliations

Soon will be listed here.

Abstract

Objective: The incidence of colorectal cancer is increasing every year, and autophagy may be related closely to the pathogenesis of colorectal cancer. Autophagy is a natural catabolic mechanism that allows the degradation of cellular components in eukaryotic cells. However, autophagy plays a dual role in tumorigenesis. It not only promotes normal cell survival and tumor growth but also induces cell death and suppresses tumors survival. In addition, the pathogenesis of various conditions, including inflammation, neurodegenerative diseases, or tumors, is associated with abnormal autophagy. The present work aimed to examine the significance of autophagy-related genes (ARGs) in prognosis prediction, to construct an autophagy prognostic model, and to identify independent prognostic factors for colorectal cancer (CRC).

Methods: This study discovered a total of 36 ARGs in CRC cases using The Cancer Genome Atlas (TCGA) and Human Autophagy-dedicated (HADd) databases along with functional enrichment analysis. Then, an autophagy prognostic model was constructed using univariate Cox regression analysis, and the key prognostic genes were screened. Finally, independent prognostic markers were determined through independent prognostic analysis and clinical correlation analysis of key genes.

Results: Of the 36 differentially expressed ARGs, 13 were related to prognosis, as determined by univariate Cox regression analysis. A total of 6 key genes were obtained by a multivariate Cox regression analysis. Independent prognostic values were shown by 3 genes, namely, microtubule-associated protein 1 light chain 3 (MAP1LC3C), small GTPase superfamily and Rab family (RAB7A), and WD-repeat domain phosphoinositide-interacting protein 2 (WIPI2) by independent prognostic analysis and clinical correlation.

Conclusions: In this study, molecular bioinformatics technology was employed to determine and construct a prognostic model of autophagy for colon cancer patients, which revealed 3 autophagy-related features, namely, MAP1LC3C, WIPI2, and RAB7A.

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References

Liao C, Ho M, Liang S, Liang C . Recombinant protein rVP1 upregulates BECN1-independent autophagy, MAPK1/3 phosphorylation and MMP9 activity via WIPI1/WIPI2 to promote macrophage migration. Autophagy. 2012; 9(1):5-19. PMC: 3542217. DOI: 10.4161/auto.22379. View

Mowers E, Sharifi M, Macleod K . Autophagy in cancer metastasis. Oncogene. 2016; 36(12):1619-1630. PMC: 5337449. DOI: 10.1038/onc.2016.333. View

Bakula D, Takacs Z, Proikas-Cezanne T . WIPI β-propellers in autophagy-related diseases and longevity. Biochem Soc Trans. 2013; 41(4):962-7. DOI: 10.1042/BST20130039. View

Tian S, Guo X, Yu C, Sun C, Jiang J . miR-138-5p suppresses autophagy in pancreatic cancer by targeting SIRT1. Oncotarget. 2017; 8(7):11071-11082. PMC: 5355247. DOI: 10.18632/oncotarget.14360. View

Liang X, Yu J, Brown K, Levine B . Beclin 1 contains a leucine-rich nuclear export signal that is required for its autophagy and tumor suppressor function. Cancer Res. 2001; 61(8):3443-9. View

Grimmel M, Backhaus C, Proikas-Cezanne T . WIPI-Mediated Autophagy and Longevity. Cells. 2015; 4(2):202-17. PMC: 4493456. DOI: 10.3390/cells4020202. View

Gafar A, Draz H, Goldberg A, Bashandy M, Bakry S, Khalifa M . Lithocholic acid induces endoplasmic reticulum stress, autophagy and mitochondrial dysfunction in human prostate cancer cells. PeerJ. 2016; 4:e2445. PMC: 5119235. DOI: 10.7717/peerj.2445. View

Guerra F, Bucci C . Role of the RAB7 Protein in Tumor Progression and Cisplatin Chemoresistance. Cancers (Basel). 2019; 11(8). PMC: 6721790. DOI: 10.3390/cancers11081096. View

Zhou H, Yuan M, Yu Q, Zhou X, Min W, Gao D . Autophagy regulation and its role in gastric cancer and colorectal cancer. Cancer Biomark. 2016; 17(1):1-10. DOI: 10.3233/CBM-160613. View

10.

Gonzalez-Gaitan M, Stenmark H . Endocytosis and signaling: a relationship under development. Cell. 2003; 115(5):513-21. DOI: 10.1016/s0092-8674(03)00932-2. View

11.

Snider M . A role for rab7 GTPase in growth factor-regulated cell nutrition and apoptosis. Mol Cell. 2003; 12(4):796-7. DOI: 10.1016/s1097-2765(03)00401-5. View

12.

Zhang C, Jiang J, Wang L, Zheng L, Xu J, Qi X . Identification of Autophagy-Associated Biomarkers and Corresponding Regulatory Factors in the Progression of Colorectal Cancer. Front Genet. 2020; 11:245. PMC: 7100633. DOI: 10.3389/fgene.2020.00245. View

13.

Zhong Z, Sanchez-Lopez E, Karin M . Autophagy, Inflammation, and Immunity: A Troika Governing Cancer and Its Treatment. Cell. 2016; 166(2):288-298. PMC: 4947210. DOI: 10.1016/j.cell.2016.05.051. View

14.

Brody H . Colorectal cancer. Nature. 2015; 521(7551):S1. DOI: 10.1038/521S1a. View

15.

Towers C, Thorburn A . Therapeutic Targeting of Autophagy. EBioMedicine. 2016; 14:15-23. PMC: 5161418. DOI: 10.1016/j.ebiom.2016.10.034. View

16.

Weiser M, Gonen M, Chou J, Kattan M, Schrag D . Predicting survival after curative colectomy for cancer: individualizing colon cancer staging. J Clin Oncol. 2011; 29(36):4796-802. PMC: 3664036. DOI: 10.1200/JCO.2011.36.5080. View

17.

Liu P, Leung C, Chang Y, Cheng J, Chen J, Weng C . ATG4B promotes colorectal cancer growth independent of autophagic flux. Autophagy. 2014; 10(8):1454-65. PMC: 4203521. DOI: 10.4161/auto.29556. View

18.

Mo S, Dai W, Xiang W, Li Y, Feng Y, Zhang L . Prognostic and predictive value of an autophagy-related signature for early relapse in stages I-III colon cancer. Carcinogenesis. 2019; 40(7):861-870. DOI: 10.1093/carcin/bgz031. View

19.

Dooley H, Razi M, Polson H, Girardin S, Wilson M, Tooze S . WIPI2 links LC3 conjugation with PI3P, autophagosome formation, and pathogen clearance by recruiting Atg12-5-16L1. Mol Cell. 2014; 55(2):238-52. PMC: 4104028. DOI: 10.1016/j.molcel.2014.05.021. View

20.

He Y, Zhang L, Tan F, Wang L, Liu D, Wang R . MiR-153-5p promotes sensibility of colorectal cancer cells to oxaliplatin via targeting Bcl-2-mediated autophagy pathway. Biosci Biotechnol Biochem. 2020; 84(8):1645-1651. DOI: 10.1080/09168451.2020.1760784. View