The expression pattern of pyroptosis-related genes predicts the prognosis and drug response of melanoma.
The expression pattern of pyroptosis-related genes predicts the prognosis and drug response of melanoma.
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DOI：
10.1038/s41598-022-24879-y
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发表时间：
2022-12-13
影响因子：
4.6
通讯作者：
Huang, Changzheng
中科院分区：
文献类型：
--
作者：
Zhou, Bin;Sha, Shanshan;Tao, Juan;Li, Jun;Shen, Chen;Zhu, Jinjin;Tan, Lulu;Dong, Liyun;Huang, Changzheng
皮肤黑色素瘤（CM，下文称为黑色素瘤）是典型地经历早期转移的高度恶性肿瘤。细胞凋亡作为一种释放炎性因子的特殊程序性细胞死亡过程，在肿瘤中已被广泛研究，但其在黑色素瘤中的作用尚未完全阐明。在这项研究中，我们通过对RNA测序数据的生物信息学分析来研究焦亡与黑色素瘤预后之间的关系。我们的研究结果表明，焦亡是一个保护性因素与黑色素瘤的预后。焦亡评分越高，总生存率越高。我们利用加权基因共表达网络分析（WGCNA）建立了一个基于12个热解相关基因的有效预后模型。然后，我们在两个独立的队列中验证了它。此外，结合临床病理特征和热解相关基因签名（PGS）评分的诺模图设计，以有效地评估黑色素瘤的预后。此外，我们分析了焦亡在肿瘤免疫微环境和药物反应中的潜在作用。有趣的是，我们发现多种免疫细胞，如CD 4 + T细胞，CD 8 + T细胞，树突状细胞和M1巨噬细胞的浸润增加可能与焦亡的发生有关。焦亡还与黑色素瘤对干扰素-α、紫杉醇、顺铂和伊马替尼的更好反应有关。通过斯皮尔曼相关性分析的12个热解相关基因和135个化疗药物的基因组学药物敏感性在癌症数据库中，我们确定溶质载体家族31成员2（SLC 31 A2）和胶原4型α 5链（COL 4A 5）与大多数这些药物的耐药性。总之，这种PGS是黑色素瘤中有效和新奇的预后指标，并且还与黑色素瘤免疫微环境和黑色素瘤治疗决策相关。
Cutaneous melanoma (CM, hereafter referred to as melanoma) is a highly malignant tumor that typically undergoes early metastasis. Pyroptosis, as a special programmed cell death process that releases inflammatory factors and has been widely studied in tumors, but its role in melanoma has not been fully elucidated. In this study, we examined the relationship between pyroptosis and the prognosis of melanoma through bioinformatic analysis of RNA-sequencing data. Our results demonstrated that pyroptosis is a protective factor associated with melanoma prognosis. A higher pyroptosis score was associated with a more favorable overall survival. We used weighted gene co-expression networks analysis (WGCNA) to establish an effective prognosis model based on 12 pyroptosis-related genes. We then validated it in two independent cohorts. Furthermore, a nomogram combining clinicopathological characteristics and a pyroptosis-related gene signature (PGS) score was designed to effectively evaluate the prognosis of melanoma. Additionally, we analyzed the potential roles of pyroptosis in the tumor immune microenvironment and drug response. Interestingly, we found that the elevated infiltration of multiple immune cells, such as CD4+ T cells, CD8+ T cells, dendritic cells, and M1 macrophages, may be associated with the occurrence of pyroptosis. Pyroptosis was also related to a better response of melanoma to interferon-α, paclitaxel, cisplatin and imatinib. Through Spearman correlation analysis of the 12 pyroptosis-related genes and 135 chemotherapeutic agents in the Genomics of Drug Sensitivity in Cancer database, we identified solute carrier family 31 member 2 (SLC31A2) and collagen type 4 alpha 5 chain (COL4A5) as being associated with resistance to most of these drugs. In conclusion, this PGS is an effective and novelty prognostic indicator in melanoma, and also has an association with the melanoma immune microenvironment and melanoma treatment decision-making.
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影响因子：
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作者：
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