Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China; Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, PR China.
Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.
Int Immunopharmacol. 2024 Aug 20;137:112411. doi: 10.1016/j.intimp.2024.112411. Epub 2024 Jun 8.
CLEC6A, (C-type lectin domain family 6, member A), plays a prominent role in regulating innate immunity and adaptive immunity. CLEC6A has shown great potential as a target for cancer immunotherapy. This study aims to explore the prognostic value of CLEC6A, and analyze the relationship associated with the common hematological parameters in breast cancer patients. We performed a retrospective analysis on 183 breast cancer patients data in hospital information system from January 2013 to December 2015. The expression of CLEC6A was recorded via semiquantitative immunohistochemistry in breast cancer. The association between expression of CLEC6A and relative parameters were performed by Chi-square test and Fisher's exact test. Kaplan-Meier assay and Log-rank test were performed to evaluate the survival time. The Cox proportional hazards regression analysis was applied to identify prognostic factors. Nomograms were conducted to predict 1-, 3-, and 5-year disease free survival (DFS) and overall survival (OS) for breast cancer, which could be a good reference in clinical practice. The nomogram model was estimated by calibration curve analysis for its function of discrimination. The accuracy and benefit of the nomogram model were appraised by comparing it to only CLEC6A via decision curve analysis (DCA). The prediction accuracy of CLEC6A was also determined by time-dependent receiver operating characteristics (TDROC) curves, and the area under the curve (AUC) for different survival time. There were 94 cases in the CLEC6A low-expression group and 89 cases in CLEC6A high-expression group. Compared to CLEC6A low-expression group, the CLEC6A high-expression group had better survival (DFS: 56.95 vs. 70.81 months, P = 0.0078 and OS: 67.98 vs. 79.05 months, P = 0.0089). The CLEC6A was a potential prognostic factor in multivariate analysis (DFS: P = 0.023, hazard ratio (HR): 0.454, 95 % confidence interval (CI): 0.229-0.898; OS: P = 0.020, HR: 0.504, 95 %CI: 0.284-0.897). The nomogram in accordance with these potential prognostic factors was constructed to predict survival and the calibration curve analysis had indicated that the predicted line was well-matched with reference line in 1-, 3-, and 5-year DFS and OS category. The 1-, 3-, and 5-year DCA curves have revealed that nomogram model yielded larger net benefits than CLEC6A alone. Finally, the TDROC curve indicated that CLEC6A could better predict 1-year DFS and OS than others. Furthermore, we combined these potential independent prognostic factors to analyze the relationship among these hematologic index and oxidative stress indicators, and indicated that higher CLEC6A level, higher CO2 level or low CHOL level or high HDL-CHO level would have survived longer and better prognosis. In breast cancer, high expression of CLEC6A can independently predict better survival. Our nomogram consisted of CLEC6A and other indicators has good predictive performance and can facilitate clinical decision-making.
CLEC6A(C 型凝集素结构域家族 6,成员 A)在调节先天免疫和适应性免疫方面发挥着重要作用。CLEC6A 作为癌症免疫治疗的靶点具有很大的潜力。本研究旨在探讨 CLEC6A 的预后价值,并分析与乳腺癌患者常见血液参数相关的关系。我们对 2013 年 1 月至 2015 年 12 月医院信息系统中 183 例乳腺癌患者的数据进行了回顾性分析。通过半定量免疫组织化学记录乳腺癌中 CLEC6A 的表达。采用卡方检验和 Fisher 确切检验分析 CLEC6A 表达与相关参数的关系。采用 Kaplan-Meier 检验和 Log-rank 检验评估生存时间。采用 Cox 比例风险回归分析识别预后因素。通过列线图预测乳腺癌的 1、3 和 5 年无病生存(DFS)和总生存(OS),为临床实践提供了很好的参考。通过校准曲线分析对列线图模型进行功能判别评估。通过决策曲线分析(DCA)将其与仅 CLEC6A 进行比较,评估列线图模型的准确性和获益。通过时间依赖的接收器操作特征(TDROC)曲线和不同生存时间的曲线下面积(AUC)来确定 CLEC6A 的预测准确性。在 CLEC6A 低表达组中有 94 例,在 CLEC6A 高表达组中有 89 例。与 CLEC6A 低表达组相比,CLEC6A 高表达组的生存情况更好(DFS:56.95 与 70.81 个月,P=0.0078 和 OS:67.98 与 79.05 个月,P=0.0089)。CLEC6A 在多变量分析中是一个潜在的预后因素(DFS:P=0.023,风险比(HR):0.454,95%置信区间(CI):0.229-0.898;OS:P=0.020,HR:0.504,95%CI:0.284-0.897)。根据这些潜在的预后因素构建了列线图来预测生存情况,校准曲线分析表明,预测线与参考线在 1、3 和 5 年 DFS 和 OS 类别中非常吻合。1、3 和 5 年 DCA 曲线表明,列线图模型比 CLEC6A 单独使用产生了更大的净收益。最后,TDROC 曲线表明,CLEC6A 能够更好地预测 1 年 DFS 和 OS。此外,我们结合这些潜在的独立预后因素,分析了这些血液学指标与氧化应激指标之间的关系,表明 CLEC6A 水平较高、CO2 水平较高或 CHOL 水平较低或 HDL-CHO 水平较高的患者生存时间更长,预后更好。在乳腺癌中,CLEC6A 的高表达可以独立预测更好的生存。我们的列线图由 CLEC6A 和其他指标组成,具有良好的预测性能,可以为临床决策提供帮助。