Pan-cancer gene expression analysis: Identification of deregulated autophagy genes and drugs to target them

Identifying suitable deregulated targets in autophagy pathway is essential for developing autophagy modulating cancer therapies. With this aim, we systematically analyzed the expression levels of genes that contribute to the execution of autophagy in 21 cancers. Deregulated genes for 21 cancers were analyzed using the level 3 mRNA data from TCGAbiolinks. A total of 574 autophagy genes were mapped to the deregulated genes across 21 cancers. PPI network, cluster analysis, gene enrichment, gene ontology, KEGG pathway, patient survival, protein expression and cMap analysis were performed. Among the autophagy genes, 260 were upregulated, and 43 were downregulated across pan-cancer. The upregulated autophagy genes -CDKN2A and BIRC5 -were the most frequent signatures in cancers and could be universal cancer biomarkers. Significant involvement of autophagy process was found in 8 cancers (CHOL, HNSC, GBM, KICH, KIRC, KIRP, LIHC and SARC). Fifteen autophagy hub genes (ATP6V0C, BIRC5, HDAC1, IL4, ITGB1, ITGB4, MAPK3, mTOR, cMYC, PTK2, SRC, TCIRG1, TP63, TP73 and ULK1) were found to be linked with patients survival and also expressed in cancer patients tissue samples, making them as potential drug targets for these cancers. The deregulated autophagy genes were further used to identify drugs Losartan, BMS-345541, Embelin, Abexinostat, Panobinostat, Vorinostat, PD-184352, PP-1, XMD-1150, Triplotide, Doxorubicin and Ouabain, which could target one or more autophagy hub genes. Overall, our findings shed light on the most frequent cancer-associated autophagy genes, potential autophagy targets and molecules for cancer treatment. These findings can accelerate autophagy modulation in cancer therapy.

Automated summary

This study identifies important autophagy genes and potential drug targets by analyzing the expression levels of genes in 21 cancers. The findings shed light on the role of autophagy in cancer and provide potential targets for cancer treatment.