[Effect of ADAM12, S100A8, and Serum Tumor Markers on Chemotherapy Outcomes and Prognosis in Patients With Triple-Negative Breast Cancer]

[ADAM12、S100A8 和血清肿瘤标志物对三阴性乳腺癌患者化疗疗效和预后的影响]

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Abstract

OBJECTIVE: To investigate the influence of a disintegrin and metalloproteinase 12 (ADAM12), S100 calcium binding protein A8 (S100A8), and serum tumor markers on chemotherapy outcomes and prognosis in patients with triple-negative breast cancer. METHODS: A totla of 300 patients with breast cancer admitted between January 2020 and January 2021 were included. Based on pathological immunohistochemistry findings, the patients were divided into a triple-negative group (n = 98, triple-negative breast cancer) and a non-triple-negative group (n = 202, non-triple-negative breast cancer). Serum tumor markers (carcinoembryonic antigen [CEA] and carbohydrate antigen 125 [CA125]), the levels of ADAM12 and S100A8, and tissue protein expression levels of ADAM12 and S100A8 were compared between the two groups. The relationship between the protein levels of ADAM12 and S100A8 in the cancer tissues and the clinicopathological characteristics of the triple-negative group was analyzed. Differences in the protein levels of ADAM12 and S100A8 between patients with different chemotherapy outcomes (remission vs. non-remission) and different follow-up outcomes (survival vs. death) were analyzed. Kaplan-Meier survival analysis was used to examine the relationship between the protein levels of ADAM12 and S100A8 in cancer tissues and the prognosis. RESULTS: The protein expression levels of ADAM12 and S100A8 in cancer tissues from the triple-negative group were higher than those in the non-triple-negative group (P < 0.05). The protein expression levels of ADAM12 and S100A8 in cancer tissues were correlated with tumor diameter, histological grading, axillary lymph node metastasis, TNM staging, and differentiation degree in the triple-negative group (P < 0.05). The levels of CEA, CA125, ADAM12, and S100A8, as well as the protein expression levels of ADAM12 and S100A8 in cancer tissues in the non-remission group, were higher than those in the remission group (P < 0.05). Similarly, these markers were also significantly elevated in the death group compared to those in the survival group (P < 0.05). After 3 years of follow-up, the overall survival (OS) of patients with low ADAM12 expression was 36.0 (8.0, 36.0) months, while that of patients with high ADAM12 expression was 32.5 (4.0, 36.0) months, showing a statistically significant difference (log rank χ (2) = 12.913, P < 0.001). The OS of patients with low S100A8 expression was 36.0 (7.0, 36.0) months, while that of the high-expression group was 31.0 (4.9, 36.0) months, also showing a statistically significant difference (log rank χ (2) = 24.151, P < 0.001). CONCLUSION: ADAM12 and S100A8 protein expression levels in triple-negative breast cancer tissues are higher than those in non- triple-negative breast cancer tissues. Serum tumor markers and ADAM12 and S100A8 protein expression levels (in both serum and tumor tissues) affect the chemotherapy outcomes and prognosis of triple-negative breast cancer patients, among which the expression levels of ADAM12 and S100A8 proteins in tumor tissues can serve as predictors of patient prognosis.

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