Yang Liyun, Liu Junzhi, Gao Yuhuan, Huang Shuixian, Wu Geping
Department of Otolaryngology, Gongli Hospital of Shanghai Pudong New Area, Shanghai 200135, P.R. China.
Department of Otolaryngology, Zhangjiagang Hospital Affiliated to Soochow University, Suzhou, Jiangsu 215600, P.R. China.
Biomed Rep. 2025 Jun 12;23(2):137. doi: 10.3892/br.2025.2015. eCollection 2025 Aug.
Thyroid cancer (THCA) is a prevalent malignancy of the head and neck region, yet the mechanisms underlying its tumorigenesis and metastasis remain poorly understood. Given that Rho GTPase activating protein 36 (ARHGAP36) has been implicated in various cellular processes related to cancer progression, including cell migration and invasion, it represents a promising candidate for further investigation in THCA. To investigate the gene expression differences in ARHGAP36 between tumor and normal tissues, the GEPIA and UALCAN databases were utilized. Various factors were also evaluated, including sample types, cancer stages, demographics, histological characteristics and nodal status. The LinkedOmics database was used to constructed a co-expression network for ARHGAP36 in THCA. Gene Ontology (GO) process enrichment analysis for ARHGAP36-associated genes was conducted via Metascape. The TIMER and TISCH databases were employed to explore the relationships between ARHGAP36 and immune markers as well as cell clusters. Functional assays were performed to assess cellular behaviors such as proliferation, migration and apoptosis. The results indicated that ARHGAP36 expression was significantly elevated in THCA tissues compared with normal tissues. Co-expression analysis revealed significant links between ARHGAP36 and key genes, including IGSF1, DPYSL3, ZCCHC12, CD97, LOXL4, CST2 and WSCD. The enriched GO processes involved T-cell immunity, particularly highlighting the association between ARHGAP36 and CD4 T cell infiltration. Notably, the downregulation of ARHGAP36 reduced tumor cell proliferation, migration and invasion while enhancing apoptosis. In conclusion, the findings of the present study indicate that ARHGAP36 plays a crucial role in facilitating immune evasion and promoting THCA progression. This underscores its potential as a diagnostic marker and therapeutic target in THCA.
甲状腺癌（THCA）是头颈部常见的恶性肿瘤，但其肿瘤发生和转移的潜在机制仍知之甚少。鉴于Rho GTP酶激活蛋白36（ARHGAP36）与包括细胞迁移和侵袭在内的与癌症进展相关的各种细胞过程有关，它是THCA进一步研究的一个有希望的候选者。为了研究肿瘤组织和正常组织中ARHGAP36的基因表达差异，利用了GEPIA和UALCAN数据库。还评估了各种因素，包括样本类型、癌症分期、人口统计学、组织学特征和淋巴结状态。使用LinkedOmics数据库构建THCA中ARHGAP36的共表达网络。通过Metascape对ARHGAP36相关基因进行基因本体（GO）过程富集分析。使用TIMER和TISCH数据库探索ARHGAP36与免疫标志物以及细胞簇之间的关系。进行功能测定以评估细胞行为，如增殖、迁移和凋亡。结果表明，与正常组织相比，THCA组织中ARHGAP36的表达显著升高。共表达分析揭示了ARHGAP36与关键基因之间的显著联系，包括IGSF1、DPYSL3、ZCCHC12、CD97、LOXL4、CST2和WSCD。富集的GO过程涉及T细胞免疫，特别突出了ARHGAP36与CD4 T细胞浸润之间的关联。值得注意的是，ARHGAP36的下调减少了肿瘤细胞的增殖、迁移和侵袭，同时增强了凋亡。总之，本研究结果表明ARHGAP36在促进免疫逃逸和THCA进展中起关键作用。这突出了其作为THCA诊断标志物和治疗靶点的潜力。
