摘要
      癌症干细胞（CSC）的出现是结肠腺癌（COAD）患者有效临床结局的障碍。自噬在CSCs干性调节中起着重要作用。然而，自噬相关基因在COAD干性中的具体作用尚不清楚。在本研究中，通过处理mRNAsi和mDNAsi两个独立的干性指数，在COAD中29个差异表达的自噬相关基因（ARGs）中，TP53INP2被确定为COAD干性消除的中枢ARGs。具有高干性指数评分的COAD患者通常表现出TP53INP2表达下调，这与比其他患者更高的化疗耐药性和较差的RFS相关。两种转录因子KLF9和SETBP1参与了CSCs TP53INP2的表达促进。此外，发现TP53INP2表达水平的降低与C4的COAD免疫亚型显著相关，这有助于TH2、Treg细胞、巨噬细胞、单核细胞和树突状细胞的低密度浸润的免疫抵抗。总之，TP53INP2被发现是高干性COAD患者预后不良的有效指标。所有这些结果将为寻找潜在的COAD治疗靶点提供一种新的策略。
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.

https://assets.researchsquare.com/files/rs-2401860/v1/3af4ecae-aac3-462b-9da6-04cb1780823b.pdf?c=1673032467