THSD7A-Mediated Breast Cancer Cell Invasion and Its Potential Role in Tumor Metastasis

Abstract

Objective: To evaluate the association between THSD7A expression and breast cancer cell invasion and metastatic behaviour and to assessed the relationship of THSD7A expression with clinicopathological characteristics and determined its independent association with metastatic disease after adjustment for potential confounding factors.

Methodology: A retrospective study was conducted on 384 breast cancer cases at MTI Hayatabad Medical Complex, Peshawar, from September 2023 to February 2024. Clinical, pathological and molecular data were collected from available records. THSD7A expression was assessed according to staining intensity, percentage positivity and expression score. Associations between THSD7A expression and tumour characteristics were analysed using Chi-square tests. Binary logistic regression was performed to identify independent predictors of metastatic disease after adjustment for age, tumour size, grade, TNM stage, hormone receptor status and Ki67 expression.

Results: Among 384 patients, high THSD7A expression was observed in 153(39.8%) cases and low expression in 231(60.2%) cases. Distant metastasis was present in 74(19.3%) patients. High THSD7A expression was significantly associated with distant metastasis compared with low expression (43(28.1%) vs 31(13.4%), p=0.001). Lymph node involvement was also higher among patients with high THSD7A expression (93(60.8%) vs 113(48.9%), p=0.029). THSD7A expression showed significant associations with extracellular matrix invasion (54(35.3%) vs 56(24.2%), p=0.017), basement membrane breakdown (46(30.1%) vs 42(18.2%), p=0.007), lymphovascular invasion (55(35.9%) vs 60(26.0%), p=0.040) and high invasion status (78(51.0%) vs 85(36.8%), p=0.008). In multivariable analysis, high THSD7A expression remained independently associated with metastasis (adjusted OR=2.410, 95% CI: 1.420–4.090, p=0.001).

Conclusion: The findings indicate that increased THSD7A expression is associated with invasive and metastatic features of breast cancer. THSD7A may represent a potential biomarker for identifying aggressive tumour behaviour; however, further multicentre and functional studies are required to confirm its prognostic and therapeutic significance.

Keywords: Breast Neoplasms; Tumour Biomarkers; Neoplasm Metastasis; Cell Invasion; Thrombospondin Type 1 Domain Containing 7A