乳腺癌中肽转运蛋白1的表达及临床病理意义

Expression of PEPT1 and its clinicopathologic significance in breast cancer

目的探讨肽转运蛋白1(peptide transporter 1,PEPT1)在乳腺癌中的表达及临床病理意义。方法利用TIMER 2.0数据库分析PEPT1在乳腺癌不同分子亚型和癌旁正常组织中的表达;通过Kaplan-Meier Plotter数据库分析其与乳腺癌预后的相关性。收集80例乳腺癌及40例癌旁正常组织蜡块及患者临床信息,采用免疫组化MaxVision法检测PEPT1的表达,分析其与临床病理特征及患者无进展生存期(progression free survival,PFS)的相关性。结果TIMER 2.0数据库分析显示,PEPT1在癌旁正常组织和乳腺癌不同亚型的表达,差异有显著性(P<0.001)。Kaplan-Meier Plotter数据库分析显示,Luminal A、Luminal B型及三阴型乳腺癌(triple negative breast cancer,TNBC)中PEPT1高表达,其20年无复发生存期(relapse-free survival,RFS)明显比低表达者长(P<0.005)。免疫组化结果显示,PEPT1高表达与乳腺癌的淋巴结转移、远处转移呈负相关(P均<0.05);TNBC中PEPT1高表达者(65.7%)明显高于非三阴型乳腺癌者(22.2%),且PEPT1高表达与TNBC患者术后化疗3年PFS呈正相关(P<0.05)。结论PEPT1在乳腺癌不同分子亚型中表达具有明显差异,在TNBC中的表达明显高于非三阴型乳腺癌,且与TNBC患者化疗预后关系密切,有望成为预测TNBC患者疗效的生物学指标。

Purpose To investigate the expression of peptide transporter 1(PEPT1)in breast cancer and to analysis its clinicopathologic significance.Methods TIMER 2.0 database was used to observe the expression of PEPT1 mRNA in different subtypes of breast cancer and adjacent non-malignant tissues.The study analyzed the correlation between PEPT1 and the prognosis of breast cancer by Kaplan-Meier Plotter database.Formalin-fixed and paraffin-embedded tissue sections of 80 breast cancer cases and 40 para-cancerous tissues were employed in the study.The expression of PEPT1 was detected by immunohistochemistry(IHC)and its correlation with clinicopathological features was analyzed.The follow-up information was collected to analyze the correlation between PEPT1 and progression-free survival(PFS).Results Data from TIMER 2.0 database revealed that the expression of PEPT1 between breast cancer tissues and different subtypes of breast cancer was statistically significant(P<0.001).Analysis by Kaplan-Meier Plotter database showed that patients with high expression of PEPT1 had higher 20-year relapse-free survival(RFS)than those with low expression in Luminal A,Luminal B,and triple negative breast cancer(TNBC)(P<0.001).Immunohistochemical results showed that high expression of PEPT1 was negatively correlated with the lymph node metastasis and distant metastasis in breast cancer(P<0.05).The high expression rate of PEPT1 in TNBC(65.7%)was higher than that non-TNBC(22.2%),and was correlated with three-year PFS of TNBC patients after postoperative chemotherapy(P<0.01).Conclusion There is a significant difference of PEPT1 expression among molecular subtype of breast cancer.The expression of PEPT1 in TNBC is significantly upregulated as compared to non-TNBC and correlate with better outcome after postoperative chemotherapy,which may be used as a novel biomarker for TNBC patients to predict clinical efficacy.