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

IF 3.8 4区医学 Q2 GENETICS & HEREDITY Current gene therapy Pub Date : 2024-11-01 DOI:10.2174/0115665232325395241018103006

Shouguang Wang, Lijuan Zhang, Dongbing Li, Miaomiao Gou

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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.

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HEPACAM2 作为结直肠癌潜在预后生物标记物和免疫疗法靶点的综合分析和实验验证

背景：HEPACAM 家族成员 2（HEPACAM2）在大肠癌（CRC）中的作用尚不明确：HEPACAM家族成员2（HEPACAM2）在结直肠癌（CRC）中的作用尚不明确：本研究的目的是对 HEPACAM2 进行广泛检查，并在 CRC 中进行实验验证：本研究利用癌症基因组图谱（TCGA）数据库中的数据，研究了HEPACAM2在CRC中的重要性及其潜在的诊断作用。此外，该研究还考察了涉及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）和药物敏感性的关联。利用GSE89076数据集进一步验证了HEPACAM2的表达，并采用定量反转录PCR（qRT-PCR）技术确认了6对CRC组织样本中HEPACAM2的表达水平：结果：HEPACAM2在包括CRC在内的多种癌症中均有异常表达。研究发现，CRC 中 HEPACAM2 表达水平的降低与 T 分期有显著相关性（p < 0.001）。HEPACAM2 在 CRC 患者中的表达减少还与总生存期（OS）较差有关（p = 0.007）。HEPACAM2在CRC患者中的表达水平被认为是一个独立的预后因素（p = 0.016）。此外，HEPACAM2 还与 TCF 依赖性信号转导、WNT、G2/M 检查点和其他通路有关。研究发现，HEPACAM2 在 CRC 中的表达与免疫浸润、免疫检查点基因、TMB / MSI 和 mRNAsi 相关。此外，HEPACAM2在CRC中的表达与对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成反比：这些研究结果表明，HEPACAM2 可作为 CRC 患者潜在的预后生物标志物和免疫治疗靶点。

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来源期刊

Current gene therapy 医学-遗传学

CiteScore

6.70

自引率

2.80%

发文量

期刊介绍： Current Gene Therapy is a bi-monthly peer-reviewed journal aimed at academic and industrial scientists with an interest in major topics concerning basic research and clinical applications of gene and cell therapy of diseases. Cell therapy manuscripts can also include application in diseases when cells have been genetically modified. Current Gene Therapy publishes full-length/mini reviews and original research on the latest developments in gene transfer and gene expression analysis, vector development, cellular genetic engineering, animal models and human clinical applications of gene and cell therapy for the treatment of diseases. Current Gene Therapy publishes reviews and original research containing experimental data on gene and cell therapy. The journal also includes manuscripts on technological advances, ethical and regulatory considerations of gene and cell therapy. Reviews should provide the reader with a comprehensive assessment of any area of experimental biology applied to molecular medicine that is not only of significance within a particular field of gene therapy and cell therapy but also of interest to investigators in other fields. Authors are encouraged to provide their own assessment and vision for future advances. Reviews are also welcome on late breaking discoveries on which substantial literature has not yet been amassed. Such reviews provide a forum for sharply focused topics of recent experimental investigations in gene therapy primarily to make these results accessible to both clinical and basic researchers. Manuscripts containing experimental data should be original data, not previously published.