白细胞介素-28受体α亚基在乳腺癌组织中的表达及其临床意义

Expression of IL-28RA in breast cancer tissues and its clinical significance

摘要:

目的 探究白细胞介素-28受体α亚基（IL-28RA）在乳腺癌组织中的表达及其临床意义。方法 选取2018年1月—2020年9月新疆医科大学第三临床医学院附属肿瘤医院收治的女性乳腺癌患者88例，均行乳腺癌根治性切除术，术后采用免疫组织化学法检测雌激素受体（ER）、孕激素受体（PR）、人类表皮生长因子受体2（HER-2）、细胞黏附分子（CAM）、肿瘤蛋白53（p53）、Ki-67、IL-28RA表达，采用实时荧光定量聚合酶链反应检测乳腺癌组织及癌旁正常组织中IL28RA mRNA的表达。术后随访3年，根据预后结局分为无疾病生存期（DFS）组和非DFS组，分析乳腺癌患者病情进展的影响因素，分析IL-28RA mRNA与乳腺癌预后的关系。结果 截至随访日期，失访9例，有效随访率为89.77%。剩余79例乳腺癌患者中非DFS 16例（25.32%）。癌组织IL-28RA mRNA相对表达量低于癌旁正常组织（P <0.05）。非DFS组TNM Ⅲ期、低分化占比高于DFS组（P <0.05）。非DFS组IL-28RA阳性表达率、IL-28RA mRNA相对表达量均低于DFS组（P <0.05）。多因素逐步Logistic回归分析结果显示：TNM分期Ⅲ期［O^R=3.688（95% CI：1.183，11.495）］、低分化［O^R=3.607（95% CI：1.157，11.246）］、IL-28RA mRNA水平高［O^R=3.865（95% CI：1.239，12.050）］是乳腺癌患者病情进展的危险因素（P <0.05）。ROC曲线结果显示，IL-28RA mRNA预测乳腺癌病情进展的截断值为0.67，敏感性为81.7%（95% CI：0.752，0.941），特异性为72.9%（95% CI：0.651，0.829）。IL-28RA mRNA低表达患者的DFS短于IL-28RA mRNA高表达患者（P <0.05）。结论 IL-28RA表达降低与乳腺癌的DFS有关。

Abstract:

Objective To explore the expression and clinical significance of interleukin-28 receptor alpha subunit (IL-28RA) in breast cancer tissues.Methods A total of 88 female breast cancer patients who were admitted to the Affiliated Cancer Hospital of the Third Clinical Medical College of Xinjiang Medical University from January 2018 to September 2020 were selected, and all of them underwent radical mastectomy. Immunohistochemistry was performed to detect the expressions of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), cell adhesion molecule (CAM), tumor protein 53 (p53), Ki-67 and IL-28RA in postoperative breast cancer tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of IL-28RA mRNA in breast cancer tissues and adjacent normal tissues. After a 3-year follow-up post-surgery, patients were divided into the disease-free survival (DFS) group and the non-DFS group based on the prognosis. Factors influencing the progression of breast cancer and the relationship between IL-28RA mRNA and prognosis of breast cancer were analyzed.Results As of the follow-up date, 9 cases were lost to follow-up, resulting in an effective follow-up rate of 89.77%. Among the remaining 79 breast cancer patients, 16 cases (25.32%) experienced disease progression (non-DFS). IL-28RA mRNA expression in cancer tissues was lower than that in adjacent normal tissues (P < 0.05). Patients in the non-DFS group had a higher proportion of TNM stage Ⅲ and poorly-differentiated tumors compared to those in the DFS group (P < 0.05). The positive expression rate of IL-28RA and the relative mRNA expression of IL-28RA were both lower in the non-DFS group compared to the DFS group (P < 0.05). The multivariable stepwise Logistic regression analysis indicated that the TNM stage Ⅲ tumor [O^R = 3.688 (95% CI: 1.183, 11.495) ], poorly-differentiated tumor [O^R = 3.607 (95% CI:1.157, 11.246) ], and high mRNA expression of IL-28RA [O^R =3.865 (95% CI:1.239, 12.050) ] were risk factors for disease progression in breast cancer patients (P < 0.05). The receiver operating characteristic curve analysis revealed that the optimal cut-off value of IL-28RA mRNA in predicting the disease progression of breast cancer was 0.67, with a sensitivity of 81.7% (95% CI: 0.752, 0.941) and a specificity of 72.9% (95% CI: 0.651, 0.829). Patients with low expression of IL-28RA mRNA had a shorter DFS compared to those with high expression of IL-28RA mRNA (P < 0.05).Conclusion The decrease in IL-28RA expression is associated with the DFS of breast cancer.