SLC10A3 对结直肠腺癌预后和免疫微环境的影响。

The impact of SLC10A3 on prognosis and immune microenvironment in colorectal adenocarcinoma.

机构信息

Digestive Endoscopy Department, The First Affiliated Hospital With Nanjing Medical University and Jiangsu Province Hospital, Nanjing, Jiangsu, China.

Gastroenterology Department, The Forth Affiliated Hospital With Nanjing Medical University, Nanjing, China.

出版信息

Eur J Med Res. 2024 Jan 4;29(1):20. doi: 10.1186/s40001-023-01526-4.

DOI:10.1186/s40001-023-01526-4

PMID:38178258

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10765936/

Abstract

BACKGROUND

SLC10A3, a gene upregulated in pan-cancer, lacks full understanding regarding its prognostic implications and association with immune infiltration in colorectal cancer (CRC). This study comprehensively analyzed SLC10A3 in CRC, evaluating its prognostic significance and influence on the tumor's immune microenvironment.

METHODS

Transcriptomic data from TCGA were obtained to compare SLC10A3 expression in both colorectal cancer (CRC) and normal tissues. Prognostic value was assessed for overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). DNA methylation patterns of SLC10A3 and correlation with DNA mismatch repair (MMR) were explored. Genetic alterations in SLC10A3 were scrutinized. The study also delved into the influence of SLC10A3 on the immune microenvironment of CRC, including immune cell infiltration and chemokines. Involvement of cancer-associated fibroblasts (CAFs) was explored. Methylation status of specific CpG islands in the SLC10A3 gene correlated with CRC patient prognosis. CRC tissue microarray was performed to verify the expression of SLC10A3 and its relationship with prognosis.

RESULTS

The research revealed that SLC10A3 is significantly upregulated in CRC and holds promise as a potential diagnostic marker. Elevated SLC10A3 expression was linked to poorer OS, DSS, and PFI. Methylation patterns of SLC10A3 displayed prognostic relevance, and genetic alterations in the gene were identified. SLC10A3 was shown to impact the immune microenvironment, with significant correlations observed between its expression and various immune cell types, chemokines, and markers associated with CAFs. Furthermore, an inverse relationship between SLC10A3 and MMR molecules was established. Methylation status of specific CpG islands within the SLC10A3 gene was associated with CRC patient prognosis. Tissue microarray showed that SLC10A3 was highly expressed in CRC and significantly correlated with poor prognosis.

CONCLUSION

The study underscores the importance of elevated SLC10A3 in CRC, associating it with decreased survival and immune infiltration, proposing it as a diagnostic biomarker and appealing immunotherapy target, given its significant overexpression and influence on the immune microenvironment and prognosis through methylation patterns.

摘要

背景

SLC10A3 是一种在多种癌症中上调的基因，但其预后意义及其与结直肠癌（CRC）免疫浸润的关系仍未得到充分理解。本研究全面分析了 SLC10A3 在 CRC 中的表达，评估了其预后意义以及对肿瘤免疫微环境的影响。

方法

从 TCGA 获得转录组数据，比较 SLC10A3 在结直肠癌（CRC）和正常组织中的表达。评估总生存期（OS）、疾病特异性生存期（DSS）和无进展间隔（PFI）的预后价值。探索 SLC10A3 的 DNA 甲基化模式及其与 DNA 错配修复（MMR）的相关性。研究 SLC10A3 的遗传改变。还研究了 SLC10A3 对 CRC 免疫微环境的影响，包括免疫细胞浸润和趋化因子。探讨了癌症相关成纤维细胞（CAFs）的参与。SLC10A3 基因特定 CpG 岛的甲基化状态与 CRC 患者的预后相关。进行了 CRC 组织微阵列以验证 SLC10A3 的表达及其与预后的关系。

结果

研究表明 SLC10A3 在 CRC 中显著上调，有望成为一种潜在的诊断标志物。SLC10A3 表达升高与 OS、DSS 和 PFI 较差相关。SLC10A3 的 DNA 甲基化模式具有预后相关性，并鉴定出该基因的遗传改变。SLC10A3 影响免疫微环境，其表达与多种免疫细胞类型、趋化因子和与 CAFs 相关的标志物之间存在显著相关性。此外，还建立了 SLC10A3 与 MMR 分子之间的负相关关系。SLC10A3 基因特定 CpG 岛内的甲基化状态与 CRC 患者的预后相关。组织微阵列显示 SLC10A3 在 CRC 中高表达，与预后不良显著相关。