Correlation between ADGRV1 expression and clinical pathological and prognostic features in breast cancer

Abstract

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.

Keywords: ADGRV1; Breast cancer; Drug sensitivity; Immune microenvironment; Methylation; Prognosis.

Fig. 1

Correlation between ADGRV1 gene expression and breast cancer. A: Box-scatter plot comparing mRNA expression of ADGRV1 between adjacent normal tissues (ANT, blue, n = 113) and all breast cancer tissues (Tumor, red, n = 1111). B: Differential mRNA expression of ADGRV1 in paired adjacent normal tissues (ANT, blue, n = 113) and breast cancer tissues (Tumor, red, n = 113). C: Distinct mRNA expression patterns of ADGRV1 in adjacent normal tissues (ANT, blue, n = 113) and four molecular subtypes of breast cancer: Luminal A (LumA, green, n = 408), Luminal B (LumB, orange, n = 329), HER2-enriched (Her2, purple, n = 108), and Basal-like (cyan, n = 196).

Fig. 2

Expression of ADGRV1 protein in breast cancer tissues. (A) H&E staining and IHC results (10× and 40× magnification) of benign tumors, LumA, LumB, Her2, and Basal-like subtypes. (B) Box plot of ADGRV1 IHC staining index in benign tumors and different molecular subtypes of malignant tumors. (C) Frequency distribution histogram of ADGRV1 IHC staining index.

Fig. 3

High expression of ADGRV1 mRNA in breast cancer tissues from TCGA data is associated with poor patient prognosis. A: Stage box plot of all breast cancer patients and adjacent normal tissues in the TCGA database. B: Stage box plot of Luminal A (LumA) breast cancer patients and adjacent normal tissues. C: Stage box plot of Luminal B (LumB) breast cancer patients and adjacent normal tissues. D: Stage box plot of HER2-enriched (Her2) breast cancer patients and adjacent normal tissues. E: Stage box plot of Basal-like breast cancer patients and adjacent normal tissues. F: Progression-free survival (PFS) curve for all TCGA breast cancer patients stratified by high/low ADGRV1 expression, with the x-axis in months. G: PFS curve for LumA breast cancer patients stratified by high/low ADGRV1 expression. H: PFS curve for LumB breast cancer patients stratified by high/low ADGRV1 expression. I: PFS curve for Her2 breast cancer patients stratified by high/low ADGRV1 expression. J: PFS curve for Basal-like breast cancer patients stratified by high/low ADGRV1 expression.

Fig. 4

Survival prognosis plots of 407 breast cancer patients from Jiangmen Maternity and Child Health Care Hospital and Jiangmen Central Hospital, stratified into ADGRV1 high/low expression groups based on IHC staining index. (A) Prognosis of all breast cancer patients. (B) Prognosis of LumA subtype. (C) Prognosis of LumB subtype. (D) Prognosis of Her2 subtype. (E) Prognosis of Basal-like subtype.

Fig. 5

Gene Set Enrichment Analysis (GSEA) results of ADGRV1 in different breast cancer subtypes. (A) Heatmap of GSEA-GO analysis. (B) Heatmap of GSEA-KEGG analysis. NES: Normalized Enrichment Score. The heatmap illustrates the magnitude of normalized enrichment scores, with black circles representing the absolute values of the normalized enrichment scores.

Fig. 6

Drug sensitivity profiles associated with high ADGRV1 expression in breast cancer tissues. (A) Heatmap of chemotherapy drug sensitivity scores. The heatmap represents log2-transformed fold changes in drug sensitivity between high/low ADGRV1 expression groups. Circles indicate three categories of p-value significance. (B) Box plot of gemcitabine sensitivity in TCGA data across all subtypes (All), HER2-enriched, and Luminal B (LumB) subtypes. (C) Box plot of 5-fluorouracil sensitivity in TCGA data across all subtypes (All) and LumB subtypes. (D) Box plot of epirubicin sensitivity in TCGA data across all subtypes (All) and LumB subtypes. (E) Box plot of lapatinib sensitivity in TCGA data across all subtypes (All) and LumB subtypes. (F) Box plot of docetaxel sensitivity in TCGA data across all subtypes (All) and LumB subtypes.

Fig. 7

Genetic and epigenetic alterations of ADGRV1 in breast cancer. (A) Mutation types of ADGRV1 in the TCGA database. (B) Mutation sites of ADGRV1 in the TCGA database. (C) Box plot comparing ADGRV1 mRNA expression levels and methylation status. (D) Heatmap of ADGRV1 methylation Beta values across molecular subtypes. (E) Correlation plot between ADGRV1 mRNA expression levels and methylation status.