Data Sheet 1_Melanocortin-1 receptor expression as a predictive factor for postoperative outcomes in melanoma patients: a retrospective study.docx

Background and objectiveThis study aims to explore the relationship between melanocortin-1 receptor (MC1R) expression levels and clinical pathological parameters of melanoma, as well as its potential as a prognostic biomarker.
MethodsThis retrospective study included 99 melanoma patients in our hospital from June 2017 to July 2023. MC1R expression was assessed by immunohistochemistry assays. Histochemistry score (H-score) determined the level of MC1R immunohistochemistry expression in melanoma. The relationships among MC1R expression, clinical pathological parameters in melanoma patients were assessed using Chi-square and Fisher’s precision probability tests. Kaplan-Meier assay and log-rank test were utilized to estimate survival curves. Potential independent factors among the enrolled patients were investigated using COX regression analysis.
ResultsAccording to median value of H-score, 38 cases with low MC1R expression and 61 cases with high MC1R expression in melanoma tumor tissues were observed. Patients with high MC1R expression in melanoma tissues exhibited a worse prognosis compared to patients with low MC1R expression. The survival time difference was statistically significant [MC1R expression in melanoma tumor tissue (MC1RT): median DFS, 12.83 vs. 17.53 months, χ2 = 5.395, P=0.0202; median OS, 16.47 vs. 21.77 months, χ2 = 5.082, P=0.0243. MC1R expression in normal adjacent to melanoma tissue (MC1RN): median DFS, 12.03 vs. 14.29 months, χ2 = 6.864, P=0.0088; median OS, 16.73 vs. 21.77 months, χ2 = 5.649, P=0.0175]. Multivariate COX regression model analysis indicated that MC1RN, MC1RT, sex, ESR, tumor site, targeted therapy, and immunotherapy were potential prognostic factors for the DFS. Furthermore, MC1RN, MC1RT, sex, tumor site, TLN, PLN, and immunotherapy were potential prognostic factors for the OS. Calibration curve indicated the predicted probabilities of nomogram models were in accordance with the actual probabilities, and the prediction accuracy was relatively high at one year and three years following surgery. The decision clinical curve revealed that the nomogram models had better predictive performance for DFS and OS than the MC1RT or MC1RN thresholds.
ConclusionsLow MC1R expression in melanoma tumor tissues and adjacent normal tissue might be beneficial for the prognosis of melanoma patients. MC1R was a predictive factor for the prognosis of melanoma patients. Nomogram models based on MC1R demonstrated good prediction ability.

研究背景与目的
本研究旨在探讨黑皮质素-1受体（melanocortin-1 receptor, MC1R）的表达水平与黑色素瘤临床病理参数的关联，及其作为预后生物标志物的潜在价值。
研究方法
本研究为回顾性研究，纳入2017年6月至2023年7月于我院就诊的99例黑色素瘤患者。采用免疫组织化学法检测MC1R的表达水平，以组织化学评分（histochemistry score, H-score）量化黑色素瘤组织中MC1R的免疫组化表达水平。采用卡方检验与Fisher确切概率法分析MC1R表达与黑色素瘤患者临床病理参数之间的相关性。采用Kaplan-Meier法绘制生存曲线，并通过log-rank检验进行生存分析。采用COX回归分析探究纳入患者的潜在独立预后因素。
研究结果
依据H-score的中位数将患者分为两组，黑色素瘤组织中MC1R低表达组38例，高表达组61例。黑色素瘤组织MC1R高表达患者的预后较低表达组更差，两组生存时间差异具有统计学意义[黑色素瘤组织MC1R表达（MC1RT）：无病生存期（disease-free survival, DFS）中位数分别为12.83个月与17.53个月，χ²=5.395，P=0.0202；总生存期（overall survival, OS）中位数分别为16.47个月与21.77个月，χ²=5.082，P=0.0243。黑色素瘤癌旁正常组织MC1R表达（MC1RN）：DFS中位数分别为12.03个月与14.29个月，χ²=6.864，P=0.0088；OS中位数分别为16.73个月与21.77个月，χ²=5.649，P=0.0175]。多因素COX回归模型分析显示，MC1RN、MC1RT、性别、红细胞沉降率（erythrocyte sedimentation rate, ESR）、肿瘤部位、靶向治疗与免疫治疗为影响DFS的潜在预后因素；而MC1RN、MC1RT、性别、肿瘤部位、区域淋巴结（tumor-lymph node, TLN）、外周淋巴结（peripheral lymph node, PLN）与免疫治疗为影响OS的潜在预后因素。校准曲线显示，列线图模型的预测概率与实际概率相符，术后1年与3年的预测准确性较高。决策曲线分析显示，基于MC1R的列线图模型对DFS与OS的预测性能优于单纯以MC1RT或MC1RN作为截断值的模型。
研究结论
黑色素瘤组织及癌旁正常组织中MC1R低表达或可改善患者预后，MC1R可作为黑色素瘤患者预后的预测因子。基于MC1R构建的列线图模型具有良好的预测能力。