HEPACAM2作为结直肠癌潜在预后生物标志物和免疫治疗靶点的综合分析与实验验证

Comprehensive Analysis and Experimental Validation of HEPACAM2 as a Potential Prognosis Biomarker and Immunotherapy Target in Colorectal Cancer.

作者信息

Wang Shouguang, Zhang Lijuan, Li Dongbing, Gou Miaomiao

机构信息

Department of General Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.

Medical Oncology Department, The Fifth Medical Center, Chinese People's Liberation Army General Hospital, Beijing 100071, China.

出版信息

Curr Gene Ther. 2024 Nov 1. doi: 10.2174/0115665232325395241018103006.

DOI:10.2174/0115665232325395241018103006

PMID:39492767

Abstract

BACKGROUND

The role of HEPACAM family member 2 (HEPACAM2) is unclear in colorectal cancer (CRC).

OBJECTIVE

The objective of this study was to perform an extensive examination of HEPACAM2 and validate it experimentally in CRC.

METHODS

This study investigated the significance of HEPACAM2 in CRC and its potential diagnostic utility utilizing data from the Cancer Genome Atlas (TCGA) database. Additionally, the study examined potential regulatory networks involving HEPACAM2, including its associations with immune infiltration, immune checkpoint genes, tumor mutational burden (TMB), microsatellite instability (MSI), mRNA expression-based stemness index (mRNAsi), and drug sensitivity in CRC. The expression of HEPACAM2 was further validated using the GSE89076 dataset, and quantitative reverse transcription PCR (qRT-PCR) was employed to confirm HEPACAM2 expression levels in six pairs of CRC tissue samples.

RESULTS

HEPACAM2 exhibited abnormal expression patterns in various types of cancer, including CRC. A decrease in HEPACAM2 expression levels in CRC was found to be significantly correlated with the T stage (p < 0.001). Reduced HEPACAM2 expression in CRC patients was also linked to poorer overall survival (OS) (p = 0.007). The expression levels of HEPACAM2 in CRC patients were identified as an independent prognostic factor (p = 0.016). Furthermore, HEPACAM2 was associated with TCF-dependent signaling in response to WNT, G2/M checkpoints, and other pathways. The expression of HEPACAM2 in CRC was found to be associated with immune infiltration, immune checkpoint genes, TMB / MSI, and mRNAsi. Additionally, the expression of HEPACAM2 in CRC was significantly and inversely correlated with the drug sensitivities to gw772405x and 6-phenyl-6h-indeno[1,2-c]isoquinoline-5,11-dione. qRT-PCR confirmed that the expression level of HEPACAM2 was found to be lowly expressed in CRC tissues.

CONCLUSION

These findings suggest that HEPACAM2 may serve as a potential prognostic biomarker and immunotherapeutic target for CRC patients.

摘要

背景

肝癌相关分子2（HEPACAM2）在结直肠癌（CRC）中的作用尚不清楚。

目的

本研究旨在对HEPACAM2进行广泛研究，并在CRC中进行实验验证。

方法

本研究利用癌症基因组图谱（TCGA）数据库的数据，研究HEPACAM2在CRC中的意义及其潜在的诊断效用。此外，该研究还检查了涉及HEPACAM2的潜在调控网络，包括其与免疫浸润、免疫检查点基因、肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）、基于mRNA表达的干性指数（mRNAsi）以及CRC药物敏感性的关联。使用GSE89076数据集进一步验证HEPACAM2的表达，并采用定量逆转录PCR（qRT-PCR）确认6对CRC组织样本中HEPACAM2的表达水平。

结果

HEPACAM2在包括CRC在内的各种癌症中表现出异常表达模式。发现CRC中HEPACAM2表达水平的降低与T分期显著相关（p < 0.001）。CRC患者中HEPACAM2表达降低也与较差的总生存期（OS）相关（p = 0.007）。CRC患者中HEPACAM2的表达水平被确定为独立的预后因素（p = 0.016）。此外，HEPACAM2与WNT、G2/M检查点及其他途径应答中的TCF依赖性信号传导相关。发现CRC中HEPACAM2的表达与免疫浸润、免疫检查点基因、TMB/MSI和mRNAsi相关。此外，CRC中HEPACAM2的表达与对gw772405x和6-苯基-6H-茚并[1,2-c]异喹啉-5,11-二酮的药物敏感性显著负相关。qRT-PCR证实CRC组织中HEPACAM2的表达水平较低。