Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Korea.
Int J Mol Sci. 2021 Nov 6;22(21):12025. doi: 10.3390/ijms222112025.
Melanoma is one of the most aggressive types of skin cancer, with significant heterogeneity in overall survival. Currently, tumor-node-metastasis (TNM) staging is insufficient to provide accurate survival prediction and appropriate treatment decision making for several types of tumors, such as those in melanoma patients. Therefore, the identification of more reliable prognosis biomarkers is urgently essential. Recent studies have shown that low immune cells infiltration is significantly associated with unfavorable clinical outcome in melanoma patients. Here we constructed a prognostic-related gene signature for melanoma risk stratification by quantifying the levels of several cancer hallmarks and identify the Wnt/β-catenin activation pathway as a primary risk factor for low tumor immunity. A series of bioinformatics and statistical methods were combined and applied to construct a Wnt-immune-related prognosis gene signature. With this gene signature, we computed risk scores for individual patients that can predict overall survival. To evaluate the robustness of the result, we validated the signature in multiple independent GEO datasets. Finally, an overall survival-related nomogram was established based on the gene signature and clinicopathological features. The Wnt-immune-related prognostic risk score could better predict overall survival compared with standard clinicopathological features. Our results provide a comprehensive map of the oncogene-immune-related gene signature that can serve as valuable biomarkers for better clinical decision making.
黑色素瘤是最具侵袭性的皮肤癌之一，总体生存率存在显著异质性。目前，肿瘤-淋巴结-转移（TNM）分期不足以为某些类型的肿瘤（如黑色素瘤患者）提供准确的生存预测和适当的治疗决策。因此，迫切需要识别更可靠的预后生物标志物。最近的研究表明，低免疫细胞浸润与黑色素瘤患者的不良临床结局显著相关。在这里，我们通过量化几种癌症特征的水平，构建了一个用于黑色素瘤风险分层的预后相关基因特征，并确定 Wnt/β-catenin 激活途径是低肿瘤免疫的主要危险因素。我们结合了一系列生物信息学和统计学方法来构建 Wnt-免疫相关的预后基因特征。使用这个基因特征，我们计算了每个患者的风险评分，以预测总生存率。为了评估结果的稳健性，我们在多个独立的 GEO 数据集上验证了该特征。最后，基于基因特征和临床病理特征建立了一个总生存相关的列线图。与标准临床病理特征相比，Wnt-免疫相关的预后风险评分可以更好地预测总生存率。我们的研究结果提供了一个全面的致癌基因-免疫相关基因特征图谱，可作为更好的临床决策的有价值的生物标志物。
