Qin Yan, Wang Lulu, Zhang Lihua, Li Jiasheng, Liao Lixian, Huang Lihaoyun, Li Wei, Yang Jianrong
Department of Health Management, The People's Hospital of Guangxi Zhuang Autonomous Region Nanning 530021, Guangxi, China.
Research Center of Health Management, Guangxi Academy of Medical Sciences Nanning 530021, Guangxi, China.
Am J Transl Res. 2022 May 15;14(5):2844-2860. eCollection 2022.
CLEC10A is expressed in a variety of cells, involved in a variety of biological pathways including immune response, and is closely related to the development of tumor immune response. However, the role of CLEC10A from a pan-cancer perspective has not yet been analyzed, and its role in human cancer prognosis and immunology remains largely unclear.
We studied the expression levels of CLEC10A and investigated its prognostic value in various cancers across distinct datasets including Oncomine, cBioPortal, and TCGA, and conducted immunohistochemical experiments using fresh bladder cancer and breast cancer samples to verify the results. In addition, we also performed GSEA of CLEC10A and explored the relationship between CLEC10A expression and immune infiltration, immune checkpoints, immune activation genes, immunosuppressive genes, chemokines and chemokine receptors.
The results showed that the expression level of CLEC10A in most tumors was significantly lower compared with non-cancerous tissue, and the decreased expression was related to poor prognosis and more advanced cancer stages. We also found that the expression of CLEC10A was significantly related to the immunomodulatory interaction between lymph and non-lymphocytes. Furthermore, the expression of CLEC10A was not only significantly correlated with the level of infiltration of CD4+T cells and CD8+T cells, but also closely related to immune checkpoints, immune activation genes, immunosuppressive genes, chemokines, and chemokine receptors. Importantly, our analysis of the relationship between CLEC10A and TMB and MSI also confirmed the speculation that CLEC10A may influence antitumor immunity by regulating the composition and immune mechanisms of the tumor microenvironment.
In conclusion, CLEC10A may serve as a new target for tumor immunotherapy and has great potential as a molecular biomarker for predicting pan-cancer prognosis and immune infiltration.
CLEC10A在多种细胞中表达，参与包括免疫反应在内的多种生物学途径，与肿瘤免疫反应的发展密切相关。然而，从泛癌角度对CLEC10A的作用尚未进行分析，其在人类癌症预后和免疫学中的作用仍 largely不清楚。
我们研究了CLEC10A的表达水平，并在包括Oncomine、cBioPortal和TCGA在内的不同数据集中调查了其在各种癌症中的预后价值，并使用新鲜的膀胱癌和乳腺癌样本进行免疫组化实验以验证结果。此外，我们还对CLEC10A进行了基因集富集分析（GSEA），并探讨了CLEC10A表达与免疫浸润、免疫检查点、免疫激活基因、免疫抑制基因、趋化因子和趋化因子受体之间的关系。
结果显示，与非癌组织相比，大多数肿瘤中CLEC10A的表达水平显著降低，且表达降低与预后不良和癌症分期更晚有关联。我们还发现，CLEC10A的表达与淋巴细胞和非淋巴细胞之间的免疫调节相互作用显著相关。此外，CLEC10A的表达不仅与CD4+T细胞和CD8+T细胞的浸润水平显著相关，还与免疫检查点、免疫激活基因、免疫抑制基因、趋化因子和趋化因子受体密切相关。重要的是，我们对CLEC10A与肿瘤突变负荷（TMB）和微卫星不稳定性（MSI）之间关系的分析也证实了以下推测，即CLEC10A可能通过调节肿瘤微环境的组成和免疫机制来影响抗肿瘤免疫。
总之，CLEC10A可能作为肿瘤免疫治疗的新靶点，作为预测泛癌预后和免疫浸润的分子生物标志物具有巨大潜力。
