Department of Hand Plastic Surgery, The First People's Hospital of Linping District, Hangzhou, China.
Department of Oncology, Huaibei People's Hospital, Anhui, China.
Medicine (Baltimore). 2022 Sep 9;101(36):e30280. doi: 10.1097/MD.0000000000030280.
Besides protecting normal cells from various internal and external perturbations, endoplasmic reticulum (ER) stress is also directly related to the pathogenesis of cutaneous melanoma (CM). However, due to the lack of specific molecular biomarkers, ER stress has not been considered a novel treatment target for CM. Here, we identified ER stress-related genes involved in the prognosis of CM patients and constructed an effective model for the prognostic prediction of these patients. First, gene expression data of CM and normal skin tissues from the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases were retrieved to identify differentially expressed ER stress-related genes in CM. Meanwhile, an independent cohort obtained from the Gene Expression Omnibus (GEO) database was used for validation. The ER stress genes (ZBP1, DIABLO, GNLY, FASLG, AURKA, TNFRSF21, and CD40LG) that were associated with CM prognosis were incorporated into our prognostic model. The functional analyses indicated that the prognostic model was correlated with patient survival, gender, and cancer growth. Multivariate and univariate Cox regressions revealed that the constructed model could serve as an independent prognostic factor for CM patients. The pathway enrichment analysis showed that the risk model was enriched in different immunity and cancer progression-associated pathways. Moreover, the signature model was significantly connected with the immune subtypes, infiltration of immune cells, immune microenvironment, as well as tumor stem cells. The gene function analysis revealed that 7 ER stress genes were differentially expressed in CM patients and were significantly associated with prognosis and several antitumor drugs. Overall, our current model presented predictive value for the prognosis of CM patients and can be further used in the development of novel therapeutic strategies for CM.
除了保护正常细胞免受各种内外扰动外，内质网（ER）应激也与皮肤黑色素瘤（CM）的发病机制直接相关。然而，由于缺乏特定的分子生物标志物，ER 应激尚未被认为是 CM 的一种新的治疗靶点。在这里，我们确定了与 CM 患者预后相关的 ER 应激相关基因，并构建了一个有效的模型来预测这些患者的预后。首先，从 Genotype-Tissue Expression（GTEx）和 The Cancer Genome Atlas（TCGA）数据库中检索了 CM 和正常皮肤组织的基因表达数据，以鉴定 CM 中差异表达的 ER 应激相关基因。同时，使用来自 Gene Expression Omnibus（GEO）数据库的独立队列进行验证。将与 CM 预后相关的 ER 应激基因（ZBP1、DIABLO、GNLY、FASLG、AURKA、TNFRSF21 和 CD40LG）纳入我们的预后模型。功能分析表明，该预后模型与患者的生存、性别和癌症生长有关。多变量和单变量 Cox 回归显示，构建的模型可以作为 CM 患者的独立预后因素。通路富集分析表明，风险模型富集在不同的免疫和癌症进展相关通路中。此外，该特征模型与免疫亚型、免疫细胞浸润、免疫微环境以及肿瘤干细胞显著相关。基因功能分析表明，7 个 ER 应激基因在 CM 患者中差异表达，与预后和几种抗肿瘤药物显著相关。总的来说，我们目前的模型对 CM 患者的预后具有预测价值，并可进一步用于开发 CM 的新型治疗策略。
