Upregulation of SQSTM۱(P۶۲) correlates with tumor progression and autophagy in gastric cancer; A bioinformatic study

Gastric cancer (GC) is the most common type of upper gastrointestinal tract cancer and is the fifth most common cancer and the third most common cause of death in worldwide. Considering the challenges of GC treatment, the use of combined drugs along with chemotherapy or surgery can be effective through various pathways, including the autophagy pathway. Autophagy has a conserved mechanism whose main role is to recycle cellular components and maintain homeostasis through the removal of undesirable proteins. Some important genes involved in autophagy are ATGs, BECLIN-۱(BECN۱), SQSTM۱(P۶۲), MAP۱LC۳(LC۳). It has been found that the expression of SQSTM۱(P۶۲) is high in early stages of the GC. Here, we aimed to explore the function of SQSTM۱(P۶۲) gene in the autophagy pathway involved in GC. Methods: Clinical information and mRNA expression levels of SQSTM۱(P۶۲) in patients with GC were obtained from The Cancer Genome Atlas (TCGA, https://portal.gdc.cancer.gov) based on the following selection criteria including basic clinical information of stage, sample types (the normal and primary tumor), nodal metastasis status and histological subtypes. All requirements were conducted on a large sample size (>۲۵۰). Datasets were then compared to obtain the significant p-value. Results: Our results indicate that the expression level of SQSTM۱(P۶۲) up-regulated in GC compared with normal tissue. This increase was the more considerable in stage ۳ of individual cancer. The TCGA analysis revealed significantly higher expression levels of the target gene in primary tumor samples compared to normal tissue. The analysis examined the nodal metastasis status (N stage) in relation to gene expression levels, revealed that N۱ is the highest expression of SQSTM۱(P۶۲). In the case of histological subtypes, the expression of SQSTM۱(P۶۲) in adenocarcinoma shows more Increase compared with adenopapillary (p-value < ۰.۰۰۱). Conclusion: Our study revealed that SQSTM۱(P۶۲) can be considered as an influential factor in GC progress with diagnostic and prognostic values.

کلیدواژه ها:

Tumor biomarkers ، Gastric cancer (GC) ، Autophagy ، SQSTM۱(P۶۲) ، The Cancer Genome Atlas (TCGA)