Tian Jun, Cao Zi-Jian, Zhang Yuan, Zhou Jin-Ke, Yang Li
Department of Dermatology, Shaanxi Provincial People's Hospital, Xi'an, 710068, China.
Department of Dermatology, The 63600 Hospital of PLA, Lanzhou, 732750, China.
Heliyon. 2023 May 9;9(5):e16153. doi: 10.1016/j.heliyon.2023.e16153. eCollection 2023 May.
Anoikis, a form of apoptosis induced by cell detachment, plays a key role in cancer metastasis. However, the potential roles of anoikis-related genes (ARGs) in assessing the prognosis of skin cutaneous melanoma (SKCM) and the tumor microenvironment (TME) remain unclear.
The data from TCGA corresponding to transcriptomic expression patterns for patients with SKCM were downloaded and utilized to screen distinct molecular subtypes by a non-negative matrix factorization algorithm. The prognostic signature was constructed by least absolute shrinkage and selection operator (LASSO) Cox regression and was validated in SKCM patients from the GEO cohort. Moreover, the relationship of the ARG_score with prognosis, tumor-infiltrating immune cells, gene mutation, microsatellite instability (MSI), and immunotherapy efficacy.
We screened 100 anoikis-related differentially expressed genes between SKCM tissues and normal skin tissues, which could divide all patients into three different subtypes with significantly distinct prognosis and immune cell infiltration. Then, an anoikis-related signature was developed based on subtype-related DEGs, which could classify all SKCM patients into low and high ARG_score groups with differing overall survival (OS) rates. ARG_score was confirmed to be a strong independent prognostic indicator for SKCM patients. By combining ARG_score with clinicopathological features, a nomogram was constructed, which could accurately predict the individual OS of patients with SKCM. Moreover, low ARG_score patients presented with higher levels of immune cell infiltration, TME score, higher tumor mutation burden, and better immunotherapy responses.
Our comprehensive analysis of ARGs in SKCM provides important insights into the immunological microenvironment within the tumor of SKCM patients and helps to forecast prognosis and the response to immunotherapy in SKCM patients, thereby making it easier to tailor more effective treatment strategies to individual patients.
失巢凋亡是一种由细胞脱离诱导的凋亡形式，在癌症转移中起关键作用。然而，失巢凋亡相关基因（ARGs）在评估皮肤黑色素瘤（SKCM）预后和肿瘤微环境（TME）中的潜在作用仍不清楚。
下载来自TCGA的与SKCM患者转录组表达模式相对应的数据，并利用非负矩阵分解算法筛选不同的分子亚型。通过最小绝对收缩和选择算子（LASSO）Cox回归构建预后特征，并在来自GEO队列的SKCM患者中进行验证。此外，还分析了ARG_score与预后、肿瘤浸润免疫细胞、基因突变、微卫星不稳定性（MSI）和免疫治疗疗效之间的关系。
我们筛选出SKCM组织与正常皮肤组织之间100个失巢凋亡相关差异表达基因，这些基因可将所有患者分为三种不同亚型，其预后和免疫细胞浸润显著不同。然后，基于亚型相关的差异表达基因开发了一种失巢凋亡相关特征，可将所有SKCM患者分为ARG_score低分组和高分组，两组总生存率（OS）不同。ARG_score被证实是SKCM患者强有力的独立预后指标。通过将ARG_score与临床病理特征相结合，构建了一个列线图，可准确预测SKCM患者的个体OS。此外，低ARG_score患者表现出更高水平的免疫细胞浸润、TME评分、更高的肿瘤突变负担和更好的免疫治疗反应。
我们对SKCM中ARGs的综合分析为SKCM患者肿瘤内的免疫微环境提供了重要见解，并有助于预测SKCM患者的预后和免疫治疗反应，从而更容易为个体患者制定更有效的治疗策略。
