4.6 Article

Low TINAGL1 expression is a marker for poor prognosis in breast cancer

Journal

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
Volume 149, Issue 8, Pages 4771-4782

Publisher

SPRINGER
DOI: 10.1007/s00432-022-04394-3

Keywords

Tubulointerstitial nephritis antigen-like 1 (TINAGL1); Breast cancer; SEC23A; Prognostic biomarker

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The expression of TINAGL1 mRNA and protein is associated with prognosis in breast cancer patients, with low expression being correlated with poorer survival. In hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer patients, low TINAGL1 expression is even worse. Low TINAGL1 mRNA expression and lymph node positivity were identified as independent factors for poor disease-free survival in breast cancer patients.
Purpose Tubulointerstitial nephritis antigen-like 1 (TINAGL1) was reported to suppress tumor metastasis and growth in triple-negative (TN) breast cancer. We aimed to determine the associations of TINAGL1 expression with clinicopathological factors and prognosis in breast cancer patients with long-term follow-up. Methods A total of 599 consecutive primary invasive breast cancer patients with available tissue specimens from surgery in our hospital were included in the study. TINAGL1 mRNA expression was examined in all 599 tissue specimens using a TaqMan real-time PCR system. TINAGL1 protein expression was further examined in 299 patients with available tissue specimens for immunohistochemical staining. Survival analyses were performed using the Kaplan-Meier method and Cox proportional hazards models. Results The median follow-up period was 12.0 years. In the total patients, low TINAGL1 mRNA expression was associated with significantly shorter disease-free survival (DFS) and overall survival than high expression (P = 0.003 and P = 0.01, respectively). Furthermore, hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer patients with low TINAGL1 mRNA expression had a worse prognosis. Multivariate analysis identified low TINAGL1 mRNA expression, combined with lymph node positivity, as an independent poor prognostic factor for DFS in invasive breast cancer patients (HR 1.41; 95% CI 1.02-1.96; P = 0.036). TINAGL1 mRNA expression also varied with menopausal status, with low TINAGL1 mRNA expression being positively associated with poor prognosis in premenopausal patients, but not in postmenopausal patients. Conclusion Our findings demonstrate that TINAGL1 may be a promising candidate biomarker and therapeutic target in breast cancer patients.

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