Insights from a Computational-Based Approach for Analyzing Autophagy Genes across Human Cancers

Genes (Basel). 2023 Jul 28;14(8):1550. doi: 10.3390/genes14081550.

Abstract

In the last decade, there has been a boost in autophagy reports due to its role in cancer progression and its association with tumor resistance to treatment. Despite this, many questions remain to be elucidated and explored among the different tumors. Here, we used omics-based cancer datasets to identify autophagy genes as prognostic markers in cancer. We then combined these findings with independent studies to further characterize the clinical significance of these genes in cancer. Our observations highlight the importance of innovative approaches to analyze tumor heterogeneity, potentially affecting the expression of autophagy-related genes with either pro-tumoral or anti-tumoral functions. In silico analysis allowed for identifying three genes (TBC1D12, KERA, and TUBA3D) not previously described as associated with autophagy pathways in cancer. While autophagy-related genes were rarely mutated across human cancers, the expression profiles of these genes allowed the clustering of different cancers into three independent groups. We have also analyzed datasets highlighting the effects of drugs or regulatory RNAs on autophagy. Altogether, these data provide a comprehensive list of targets to further the understanding of autophagy mechanisms in cancer and investigate possible therapeutic targets.

Keywords: autophagy; cancer; cancer dataset; cell phenotype; systems biology.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / genetics
  • Clinical Relevance
  • Cluster Analysis
  • Humans
  • Neoplasms* / genetics
  • RNA

Substances

  • RNA

Grants and funding

This research was funded by grants #2019/05583-0 (Fundação de Amparo à Pesquisa do Estado de São Paulo, FAPESP to A.G.M.C. and R.C.), 305239/2022-8 (Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq to R.C.), and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil (CAPES)—Finance Code 001 (A.G.M.C., R.C., G.G. and A.F.R.).