ARHGAP36 serves as a diagnostic and therapeutic marker that mediates immune escape and promotes thyroid cancer metastasis

Yang,Liyun; Liu,Junzhi; Gao,Yuhuan; Huang,Shuixian; Wu,Geping

doi:10.3892/br.2025.2015

ARHGAP36 serves as a diagnostic and therapeutic marker that mediates immune escape and promotes thyroid cancer metastasis

Authors:
- Liyun Yang
- Junzhi Liu
- Yuhuan Gao
- Shuixian Huang
- Geping Wu
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Affiliations: Department of Otolaryngology, Gongli Hospital of Shanghai Pudong New Area, Shanghai 200135, P.R. China, Department of Clinical Medicine, Medical College of Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China, Department of Otolaryngology, Zhangjiagang Hospital Affiliated to Soochow University, Suzhou, Jiangsu 215600, P.R. China
Published online on: June 12, 2025 https://doi.org/10.3892/br.2025.2015
Article Number: 137
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 in vitro 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.

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