Zhang Chiyuan, Guo Cuishan, Li Yan, Liu Kuiran, Zhao Qi, Ouyang Ling
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
School of Computer Science and Software Engineering, University of Science and Technology Liaoning, Anshan, China.
Front Cell Dev Biol. 2021 Aug 2;9:726656. doi: 10.3389/fcell.2021.726656. eCollection 2021.
Claudin-6 (CLDN6) is one of the 27 family members of claudins and majorly involved in the tight junction and cell-to-cell adhesion of epithelial cell sheets, playing a significant role in cancer initiation and progression. To provide a more systematic and comprehensive dimension of identifying the diverse significance of CLDN6 in a variety of malignant tumors, we explored CLDN6 through multiple omics data integrative analysis, including gene expression level in pan-cancer and comparison of CLDN6 expression in different molecular subtypes and immune subtypes of pan-cancer, targeted protein, biological functions, molecular signatures, diagnostic value, and prognostic value in pan-cancer. Furthermore, we focused on uterine corpus endometrial carcinoma (UCEC) and further investigated CLDN6 from the perspective of the correlations with clinical characteristics, prognosis in different clinical subgroups, co-expression genes, and differentially expressed genes (DEGs), basing on discussing the validation of its established monoclonal antibody by immunohistochemical staining and semi-quantification reported in the previous study. As a result, CLDN6 expression differs significantly not only in most cancers but also in different molecular and immune subtypes of cancers. Besides, high accuracy in predicting cancers and notable correlations with prognosis of certain cancers suggest that CLDN6 might be a potential diagnostic and prognostic biomarker of cancers. Additionally, CLDN6 is identified to be significantly correlated with age, stage, weight, histological type, histologic grade, and menopause status in UCEC. Moreover, CLDN6 high expression can lead to a worse overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in UCEC, especially in different clinical subgroups of UCEC. Taken together, CLDN6 may be a remarkable molecular biomarker for diagnosis and prognosis in pan-cancer and an independent prognostic risk factor of UCEC, presenting to be a promising molecular target for cancer therapy.
Claudin-6（CLDN6）是claudin家族27个成员之一，主要参与上皮细胞层的紧密连接和细胞间黏附，在癌症的发生和发展中发挥重要作用。为了更系统、全面地了解CLDN6在多种恶性肿瘤中的不同意义，我们通过多组学数据综合分析对CLDN6进行了探索，包括泛癌中的基因表达水平、泛癌不同分子亚型和免疫亚型中CLDN6表达的比较、靶向蛋白、生物学功能、分子特征、诊断价值和预后价值。此外，我们聚焦于子宫内膜癌（UCEC），在前一项研究报道的免疫组织化学染色和半定量验证其已建立的单克隆抗体的基础上，进一步从与临床特征、不同临床亚组的预后、共表达基因和差异表达基因（DEG）的相关性角度研究CLDN6。结果表明，CLDN6的表达不仅在大多数癌症中存在显著差异，而且在癌症的不同分子和免疫亚型中也有显著差异。此外，CLDN6在预测癌症方面具有较高的准确性，并且与某些癌症的预后显著相关，这表明CLDN6可能是一种潜在的癌症诊断和预后生物标志物。此外，在UCEC中，CLDN6被确定与年龄、分期、体重、组织学类型、组织学分级和绝经状态显著相关。此外，CLDN6高表达可导致UCEC患者的总生存期（OS）、疾病特异性生存期（DSS）和无进展生存期（PFI）更差，尤其是在UCEC的不同临床亚组中。综上所述，CLDN6可能是泛癌诊断和预后的重要分子生物标志物，也是UCEC的独立预后危险因素，有望成为癌症治疗的分子靶点。
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