Aberrant promoter methylation of PCDH10 as a potential diagnostic and prognostic biomarker for patients with breast cancer

PCDH10 启动子异常甲基化可作为乳腺癌患者的潜在诊断和预后生物标志物

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作者:Wentao Liu, Jin Wu, Guangyue Shi, Xiaolong Yue, Dan Liu, Qingyuan Zhang

Abstract

Protocadherin-10 (PCDH10) is a tumor suppressor gene. Its expression level is downregulated by promoter methylation in certain types of human tumors. The aim of the present study was to examine the expression level and promoter methylation status of PCDH10 in breast cancer cells and to evaluate the association of PCDH10 methylation and tumor progression and prognosis. MethyLight was used to detect the methylation status of PCDH10 in breast cancer tissues and healthy breast tissues. Reverse transcription-quantitative polymerase chain reaction was used to assess the mRNA expression level of PCDH10, as well as to evaluate the association between PCDH10 methylation and clinicopathological features, along with patients' overall survival (OS). PCDH10 5'-C-phosphate-G-3' (CpG) methylated sites were identified in tumor tissues and matched healthy tissues (n=392). Tumor tissues and matched healthy tissues exhibited identifiable PCR results, with PCDH10 gene promoter methylation identified in ductal carcinoma in situ (66%), invasive ductal carcinoma (82%), invasive ductal carcinoma with lymph node metastasis (85.32%) and hereditary breast cancer tissues (72.37%). PCDH10 mRNA expression was significantly decreased in breast cancer tissues compared with healthy breast tissues (P=0.032). PCDH10 methylation was associated with tumor size (P=0.004), but not associated with other clinical factors. Survival analysis revealed that the patients exhibiting methylated-PCDH10 had significantly poorer OS times than patients exhibiting unmethylated-PCDH10 (P<0.0001). Receiver operating characteristic analysis indicated a sensitivity of 75%, a specificity of 62.5%, and an area under the curve of 0.682 for PCDH10. Additionally, the results of the present study indicated that PCDH10 methylation status may be a useful diagnostic and prognostic evaluation biomarker for breast cancer. The results suggested that PCDH10 methylation is a common occurrence in primary breast cancer and is associated with poor survival rates among patients with breast cancer.

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