Abstract
Gastrointestinal (GI) cancers are among the most fatal diseases in the world. Numerous studies have demonstrated the relationship between autophagy and development of gastrointestinal cancers. However, whether autophagy-related genes can predict prognosis of GI cancers in individuals of Asian ancestry has not been defined. This study, evaluated the prognostic value of autophagy-related genes in gastrointestinal cancer. Expression profile of autophagy-related genes for 296 gastrointestinal cancer patients of Asian ancestry was downloaded from the TCGA database (TCGA-LIHC, TCGA-STAD, TCGA-ESCA, TCGA-PAAD, TCGA-COAD, TCGA-CHOL, and TCGA-READ). The prognostic value of the autophagy-related genes was evaluated using univariate Cox, LASSO, and multivariate Cox regression analyses. The risk score of the autophagy-related gene signature was calculated to assess its predictive prognostic value for GI cancers. Forty-seven differentially expressed autophagy-related genes, in Asian patients with gastrointestinal cancers, were identified. Of the 47 genes, 4 were associated with prognosis of GI cancer (SQSTM1, BIRC5, NRG3, and CXCR4). A prognostic model for GI cancer, based on the expression of the above 4 genes in the training set, showed that cancer patients were stratified into high-risk and low-risk groups (P < 0.05). The utility of the model for overall survival (OS) of GI cancer patients was consistent across the entire set, training set, and test set (entire set: P = 4.568 × 10−4; train set: P = 5.718 × 10−3; test set: P = 3.516 × 10−2). The sensitivity and specificity of the ROC curve of the above prognostic model in predicting the 5-year prognosis of GI cancer was satisfactory (entire set: 0.728; train set: 0.727; test set: 0.733). Analysis of clinical samples validated the overexpression of the 4 genes (SQSTM1, BIRC5, NRG3, and CXCR4) in tumor tissues relative to paired normal tissues, consistent with bioinformatic findings. Expression of the 4 autophagy-related genes (SQSTM1, BIRC5, NRG3, and CXCR4) can accurately predict the prognosis of gastrointestinal tumors in Asian patients.
Highlights
Digestive tract diseases are currently some of the most serious health problems worldwide
The mRNA expression profiles and the corresponding clinical data of 296 GI cancer patients of Asian ancestry were obtained from the The Cancer Genome Atlas (TCGA) dataset
The Gene Ontology (GO) enrichment analyses revealed that the differently expressed genes (DEGs) participated in autophageal processes, macroautophagy, neuron death, and intrinsic apoptotic signaling pathway
Summary
Digestive tract diseases are currently some of the most serious health problems worldwide. Aided by ATGs, autophagosomes fuse with the lysosome to form autolysomoses, which release the monomembranous particles that degrade the target materials [7] This pathway is regulated by numerous molecules including core ATG protein, master cell growth regulator serine/threonine kinase mTOR, Beclin, and antiapoptotic molecule BCL2 [8]. Identifying autophagy-related genes may unravel the genetic prognostic indicators for GI cancers It may form a basis upon which novel drugs that address the different patient responses to chemotherapy can be developed. In the past two years, many studies have provided new evidence for tumor therapy response using prognostic prediction models of autophagy-related genes. A five autophagy-related gene model that independently predicts the OS of endometrial cancer (EC) patients has been developed [16]. The sensitivity and specificity of this model were validated using several patient datasets
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