Department of Anesthesiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfengdong Road, Guangzhou 510060, China.
Guangdong Esophageal Cancer Institute, Guangzhou 510060, China.
Comput Math Methods Med. 2022 Aug 25;2022:6495301. doi: 10.1155/2022/6495301. eCollection 2022.
Acyl-CoA synthetase long-chain family member 4 (ACSL4) has been linked to the occurrence of tumors and is implicated in the ferroptosis process. Deep learning has been applied to many areas in health care, including imaging diagnosis, digital pathology, classification of cancer, and prediction of metastasis. Nonetheless, neither the level of ACSL4 expression nor its predictive significance in non-small-cell lung cancer (NSCLC) is well understood at this time. Predictions of the ACSL4 mRNA expressions in NSCLC and its link to NSCLC prognosis were made with the aid of the Oncomine and TCGA databases. By performing real-time PCR, we detected the levels of ACSL4 expression that were present in human NSCLC samples. Analyses of the diagnostic, as well as the prognostic significance of ACSL4 in NSCLC, were performed with the use of Kaplan-Meier curves. To assess the influence of ACSL4 on ferroptosis in NSCLC cell lines, an inducer of ferroptosis, namely, erastin, was utilized in this study. In NSCLC tissues, there was a substantial decrease in the level of ACSL4 expression ( < 0.001), and this was in line with the findings of the inquiry into the Oncomine and TCGA databases. After that, the findings of the immunohistochemistry analysis revealed that the ACSL4 staining was weakened in NSCLC samples in contrast with the normal samples. It was shown that the differential expression of ACSL4 was substantially linked to the stages of cancer, smoking behaviors, and the status of nodal metastases (all < 0.001). According to the findings of the survival analysis, both RFS and OS were favorable among NSCLC patients who had elevated expression of ACSL4. The ferroptosis sensitization in cancer cells may be reestablished with upregulation of ACSL4 through gene transfection. Mechanistically, protein ubiquitination could perform a remarkable function in ACSL4-induced ferroptosis. ACSL4, which has a function in ferroptosis as both a contributor and monitor, was shown to be downregulated in NSCLC. This finding suggests that ACSL4 might function as a helpful diagnostic and prognostic biological marker and might also be considered a novel possible treatment target for NSCLC.
酰基辅酶 A 合成酶长链家族成员 4（ACSL4）与肿瘤的发生有关，并与铁死亡过程有关。深度学习已应用于医疗保健的许多领域，包括成像诊断、数字病理学、癌症分类和转移预测。尽管如此，目前对于非小细胞肺癌（NSCLC）中 ACSL4 的表达水平及其预测意义仍了解甚少。借助 Oncomine 和 TCGA 数据库，对 NSCLC 中 ACSL4 mRNA 的表达及其与 NSCLC 预后的关系进行了预测。通过实时 PCR 检测了人 NSCLC 样本中 ACSL4 表达的水平。使用 Kaplan-Meier 曲线分析了 ACSL4 在 NSCLC 中的诊断和预后意义。为了评估 ACSL4 对 NSCLC 细胞系中铁死亡的影响，本研究使用了铁死亡诱导剂 erastin。在 NSCLC 组织中，ACSL4 表达水平显著降低（<0.001），这与 Oncomine 和 TCGA 数据库的研究结果一致。随后，免疫组化分析的结果显示，与正常样本相比，NSCLC 样本中 ACSL4 染色减弱。结果表明，ACSL4 的差异表达与癌症分期、吸烟行为和淋巴结转移状态密切相关（均<0.001）。根据生存分析的结果，ACSL4 高表达的 NSCLC 患者的 RFS 和 OS 均较好。通过基因转染上调 ACSL4 可以重新建立癌细胞的铁死亡敏感性。ACSL4 作为铁死亡的促进剂和监测器，其蛋白泛素化在 ACSL4 诱导的铁死亡中发挥着重要作用。ACSL4 在 NSCLC 中下调，这表明 ACSL4 可能作为一种有帮助的诊断和预后生物标志物发挥作用，也可能被视为 NSCLC 的一种新的潜在治疗靶点。
