Zhenduanxue lilun yu shijian (Apr 2024)
The clinicopathologic significance of AR, SKP2, SOX10, PD-L1 and TILs expression in triple-negative breast cancer
Abstract
Objective To explore the expression of androgen receptor (AR), S-phase kinase associated protein 2 (SKP2), Sry-related HMG box-containing factor 10 (SOX10), programmed death-ligand 1 (PD-L1) and tumor infiltrating lymphocytes (TILs) in triple-negative breast cancer (TNBC) and their relationships with clinical prognosis. Methods The proportion of TILs in 109 TNBCs was assessed on Hematoxylin-eosin stained sections ，and Leica Bond-Max automatic immunohistochemistry apparatus was used to detect the expressions of AR,SKP2,SOX10 and PD-L1 in TNBC tissue. The relationship between the above indicators and clinicopathological charactersitics was analyzed. Univariate survival analysis was performed by Kaplan-Meier, and survival by Log rank test. Multivariate survival analysis was performed by cox regression model. Results A total of 95 patients were followed-up with a median follow-up time of 48 months. For 95patients,the median disease-free survival (DFS) time was 42 months, and median overall survival (OS) time were 48 months. In TNBC, the expression of AR was associated with negative lymph node metastasis, maximum tumor diameter <2 cm. High expression of TILs was associated with low grade TNBC. The expression of SKP2 was associated with positive nerve/vasculature invasion and high grade TNBC. The expression of SOX10 was associated with high grade TNBC and positive lymph node metastasis. The expression of PD-L1 was associated with positive lymph node metastasis, positive nerve/vascular invasion, and high grade TNBC (all the P<0.05 as above). Survival analysis demonstrated that the positive expression of SKP2 or AR SOX10 was correlated with worse DFS (P=0.007、P<0.001) and OS (P=0.013、P<0.001), and patients with high expression of TILs showed better DFS (P=0.016) and OS (P=0.004). TNBC patients with AR+/SKP2- or AR+/SOX10- had better DFS (P=0.004、P<0.001) and OS (P=0.007、P<0.001), while those with SOX10+/low TILs or PD-L1+/low TILs had worse DFS (P=0.000、P=0.008) and OS (P=0.001、P=0.002), and AR-/low TILs had worse OS (P=0.014). Multivariate survival analysis showed positive expression SKP2 (HR=4.143, 95%CI 1.578-10.875), or SOX10 (HR=7.578, 95%CI 2.067-27.782) were independent prognostic factors for worse DFS, postive expression SKP2 (HR=3.758, 95%CI 1.400-10.084), or SOX10 (HR=5.131, 95%CI 1.316-20.000)， were independent prognostic factors for worse OS (all the P<0.05 as above) and higher TILs(HR=0.375,95%CI 0.154-0.917) was independent prognostic factors for better OS(all the P<0.05 as above). Conclusions High expression of AR and TILs in TNBC indicate better prognosis, while SKP2, SOX10 and PD-L1 expression demonstrate more aggressive clinicopathological features in TNBC. The expression of SKP2, SOX10 and TILs in TNBC are associated with prognosis, suggesting that these indicators may serve as new prognostic factors and potential therapeutic targets in TNBC.
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