OCLN 作为肾透明细胞癌预后和免疫浸润的新型生物标志物：综合计算和实验特征分析。
OCLN as a novel biomarker for prognosis and immune infiltrates in kidney renal clear cell carcinoma: an integrative computational and experimental characterization.
机构信息
Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Center for Systems Biology, Department of Bioinformatics, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China.
出版信息
Front Immunol. 2023 Sep 22;14:1224904. doi: 10.3389/fimmu.2023.1224904. eCollection 2023.
BACKGROUND
Occludin (OCLN) is an important tight junction protein and has been reported to be abnormally expressed in the development of malignant tumors. However, its biomarker and carcinogenic roles in kidney renal clear cell carcinoma (KIRC) are less investigated.
METHODS
The Cancer Genome Atlas database and Human Protein Atlas database were used to analyze the expression of OCLN in KIRC. UALCAN database and methylation-specific PCR assay were used to evaluate the methylation level of OCLN in KIRC. Univariate and multivariate Cox regression analyses were performed to model the prognostic significance of OCLN in KIRC patient cohorts. The correlation between OCLN expression and the immune cell infiltration, immune-related function and immune checkpoints were explored. Finally, EdU, scratch assay and transwell experiments were conducted to validate the role of OCLN in KIRC development.
RESULTS
The expression of OCLN was significantly downregulated in KIRC, compared with normal renal tissues (p<0.001). Patients with low OCLN expression showed a worse prognosis and poorer clinicopathological characteristics. Functional enrichment analysis revealed that OCLN was mainly involved in biological processes such as immune response, immunoglobulin complex circulating and cytokine and chemokine receptor to mediate KIRC development. Immune-related analysis indicated that OCLN could potentially serve as a candidate target for KIRC immunotherapy. OCLN overexpression inhibited proliferation, migration and invasion of KIRC cells .
CONCLUSION
OCLN was validated as a candidate prognostic biomarker and therapeutic target of KIRC based both on computational and experimental approaches. More experiments will be conducted to decode its molecular mechanism in KIRC carcinogenesis in the future work.
背景
紧密连接蛋白 Occludin（OCLN）是一种重要的紧密连接蛋白，其在恶性肿瘤的发展过程中表达异常。然而，其在肾透明细胞癌（KIRC）中的生物标志物和致癌作用研究较少。
方法
使用癌症基因组图谱数据库和人类蛋白质图谱数据库分析 OCLN 在 KIRC 中的表达。使用 UALCAN 数据库和甲基化特异性 PCR 检测评估 OCLN 在 KIRC 中的甲基化水平。使用单变量和多变量 Cox 回归分析模型评估 OCLN 在 KIRC 患者队列中的预后意义。探索 OCLN 表达与免疫细胞浸润、免疫相关功能和免疫检查点的相关性。最后，通过 EdU、划痕实验和 Transwell 实验验证 OCLN 在 KIRC 发展中的作用。
结果
与正常肾组织相比，OCLN 在 KIRC 中的表达显著下调（p<0.001）。OCLN 低表达的患者预后较差，临床病理特征较差。功能富集分析表明，OCLN 主要参与免疫反应、免疫球蛋白复合物循环、细胞因子和趋化因子受体等生物学过程，介导 KIRC 的发展。免疫相关分析表明，OCLN 可能是 KIRC 免疫治疗的候选靶点。OCLN 过表达抑制 KIRC 细胞的增殖、迁移和侵袭。
结论
基于计算和实验方法，验证了 OCLN 是 KIRC 的候选预后生物标志物和治疗靶点。未来的工作将进行更多的实验来解码其在 KIRC 致癌中的分子机制。
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