Wang Lili, He Jiadi, Chen Jiaqing, Zeng Xueqing, Lu Wenjie, Qiu Yulan, Zhong Meigong, Li Qiuli, Long Qisheng, Ren Liangliang, Zhang Xin, Lu Yuanzhi
Department of Clinical Pathology, Jiangmen Maternity and Child Health Care Hospital, Jiangmen, 529099, Guangdong, People's Republic of China.
Jiangmen Key Laboratory of Precision and Clinical Translation Medicine, Clinical Experimental Center, Jiangmen Engineering Technology Research Center of Clinical Biobank and Translational Research, Jiangmen Central Hospital, Jiangmen, 529030, People's Republic of China.
Sci Rep. 2025 Jun 5;15(1):19738. doi: 10.1038/s41598-025-04695-w.
Breast cancer, a leading global health threat with rising incidence, demands precision medicine guided by molecular subtyping. ADGRV1, an adhesion G protein-coupled receptor gene implicated in tumorigenesis but unexplored in breast cancer, was investigated using TCGA data (1,231 cases) and a local cohort (408 cases). While ADGRV1 showed no differential expression between tumors and normal tissues (P = 0.210), it was significantly downregulated in basal-like subtypes (P < 0.001). The association between high ADGRV1 expression and poor prognosis remains significant in the overall cohort as well as within individual molecular subtype. Functional enrichment analyses linked ADGRV1 to ribosome suppression, ECM remodeling (positive ECM-receptor interaction), and immunosuppression (negative immune pathway regulation), suggesting its role in tumor metastasis. Drug sensitivity assays demonstrated ADGRV1-high tumors confer resistance to lapatinib, gemcitabine, and 5-fluorouracil, particularly in LumB subtypes. Mechanistically, copy number variations and promoter methylation (Pearson r =-0.45, P < 0.001) regulated ADGRV1 expression, with basal-like tumors showing hypermethylation-associated suppression. These findings position ADGRV1 as a prognostic biomarker and potential therapeutic target, highlighting its dual role in tumor microenvironment modulation and drug resistance.
乳腺癌是一种全球主要的健康威胁，其发病率不断上升，需要分子亚型指导下的精准医学。ADGRV1是一种参与肿瘤发生但在乳腺癌中未被研究的粘附G蛋白偶联受体基因，我们使用TCGA数据（1231例）和一个本地队列（408例）对其进行了研究。虽然ADGRV1在肿瘤组织和正常组织之间没有差异表达（P = 0.210），但在基底样亚型中显著下调（P < 0.001）。在整个队列以及各个分子亚型中，ADGRV1高表达与不良预后之间的关联仍然显著。功能富集分析将ADGRV1与核糖体抑制、细胞外基质重塑（正向细胞外基质-受体相互作用）和免疫抑制（负向免疫途径调节）联系起来，表明其在肿瘤转移中的作用。药物敏感性试验表明，ADGRV1高表达的肿瘤对拉帕替尼、吉西他滨和5-氟尿嘧啶具有抗性，尤其是在LumB亚型中。从机制上讲，拷贝数变异和启动子甲基化（Pearson r = -0.45，P < 0.001）调节ADGRV1的表达，基底样肿瘤表现出与高甲基化相关的抑制。这些发现将ADGRV1定位为一种预后生物标志物和潜在的治疗靶点，突出了其在肿瘤微环境调节和耐药性中的双重作用。
