Identification of autophagy-related genes for regulating cancer stem cell characteristics in colon adenocarcinoma by the analysis of transcriptome data stemness indices

Abstract

The emergence of cancer stem cells (CSCs) is the barrier to effective clinical outcomes for Colon adenocarcinoma (COAD) patients. Autophagy was found to play an important role on CSCs stemness regulation. However, the specific role of autophagy-related genes in COAD stemness remains unclear. In this study, by processing on two independent stemness indices, mRNAsi and mDNAsi, TP53INP2 among 29 differentially expressed autophagy-related genes(ARGs) in COAD was identified to be the hub ARGs in COAD stemness elimination. COAD patients with high stemness indices scores usually showed a down-regulated TP53INP2 expression which was correlated to a higher chemotherapy resistance and poorer RFS than the others. Two TFs, KLF9 and SETBP1 were involved in CSCs TP53INP2 expression promotion. Additionally, the decreased expression level of TP53INP2 was found to be significantly correlated to the COAD immune subtypes of C4 which contributed to the immunoresistance with low density infiltration of TH2, Treg cells, macrophages, monocyte and dendritic cells. In conclusion, TP53INP2 was found to be a valid indicator for poor prognosis of COAD patients with high stemness. All these results would provide a new strategy in seeking potential COAD therapeutic targets.