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. 2020 May 14:2020:5209695.
doi: 10.1155/2020/5209695. eCollection 2020.

Effect of COL4A1 Expression on the Survival of Neoadjuvant Chemotherapy Breast Cancer Patients

Shin-Mae Wang  1 , Po-Ming Chen  2   3 , Yu-Wen Sung  4 , Wei-Chieh Huang  3 , Hung-Sen Huang  3 , Pei-Yi Chu  5   6   7
Affiliations

Effect of COL4A1 Expression on the Survival of Neoadjuvant Chemotherapy Breast Cancer Patients

Shin-Mae Wang et al. J Oncol. .

Abstract

Optimal therapy for each patient depends on their subtype, anatomic cancer stage, gene status, and preferences. Neoadjuvant chemotherapy-treated tumors have shown attenuated tumor growth, but the therapy cannot completely reduce tumor cell dissemination to blood stream and distant metastasis. Though it has been indicated that the protein of the collagen type IV alpha 1 (COL4A1) gene is induced by p53 to inhibit angiogenesis and tumorigenic activity in cancer cells, its prognostic significance in breast cancer (BC) patients has not yet been fully elucidated. We analysed 206 BC and fresh paired-match adjacent normal breast tissue from tissue microarrays (TMAs) and COL4A1-stained TMAs using immunohistochemistry. These were used to evaluate COL4A1 expression in BC and to analyse the relationship between this expression and clinicopathological factors and prognosis. The expression of the COL4A1 protein was significantly higher in normal adjacent tissue than in the tumor tissues of BC (P < 0.0001). The low COL4A1 expression of the BC patients had decreased metastasis incidence ratio than those exhibiting high COL4A1 expression (P=0.034). Low COL4A1 expression in the tumor cells of BC patients was found to significantly reduce the overall survival (OS) and relapse-free survival (RFS) rates of neoadjuvant chemotherapy patients (P=0.047 and P=0.025, respectively). We also validated the results to ensure their consistency with a web server program for survival analysis from the Cancer Genome Atlas (TCGA) database (P=0.057). Additionally, COL4A1 expression was positively correlated with p53 expression (P=0.00076). Thus, we present clinical evidence that COL4A1 expression can be used as a biomarker of better prognosis of BC patients receiving neoadjuvant chemotherapy.

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Conflict of interest statement

The authors confirm that there are no conflicts of interest associated with this publication.

Figures

Figure 1
Figure 1
COL4A1 expression in adjacent normal and tumor breast tissue of BC patients. (a) Representative high COL4A1 immunostaining results in adjacent normal breast tissue. (b) Representative high COL4A1 immunostaining results in breast cancer tissue. (c) t-test for COL4A1 levels was compared in tumor and pair matched nontumor breast tissues of BC patients.
Figure 2
Figure 2
Kaplan–Meier analysis of different characteristics for patients. (a) Overall survival estimates for age. (b) Overall survival estimates for tumor stage. (c) Overall survival estimates for ER. (d) Overall survival estimates for PR. (e) Overall survival estimates for HER2. (f) Overall survival estimates for tumor metastasis. (g) Overall survival estimates for neoadjuvant chemotherapy. (h) Overall survival estimates for COL4A1 expression.
Figure 3
Figure 3
Cox regression analysis for the influence of parameters and COL4A1 on overall survival in all BC patients. Statistical tests were two sided. HR = hazard ratio and CI = confidence interval.
Figure 4
Figure 4
Kaplan–Meier analysis for the influence of COL4A1 expression, stage, and age on overall survival (OS) and relapse-free survival (RFS) in BC patients with neoadjuvant chemotherapy. (a) Overall survival estimates for COL4A1 expression. (b) Overall survival estimates for stage. (c) Overall survival estimates for age. (d) Relapse-free survival estimates for COL4A1 expression. (e) Relapse-free survival estimates for stage. (f) Relapse-free survival estimates for age.
Figure 5
Figure 5
The web server for the COL4A1 expression analysis. (a) Pearson's correlation for p53 and COL4A1 expression. (b) Kaplan–Meier analysis of the influence of and COL4A1 expression on overall survival (OS) in BC patients with neoadjuvant chemotherapy.
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