Wang Qilong, Sun Nannan, Zhang Mingzhi
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China.
The Academy of Medical Science of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.
Int J Gen Med. 2023 May 16;16:1833-1844. doi: 10.2147/IJGM.S409006. eCollection 2023.
Lung adenocarcinoma (LUAD) is an aggressive cancer that has an extremely poor prognosis. As well as facilitating the detachment of cancer cells from the primary tumor site, anoikis plays an important role in cancer metastasis. Few studies to date, however, have examined the role of anoikis in LUAD, in patient prognosis.
A total of 316 anoikis-related genes (ANRGs) integrated from Genecards and Harmonizome portals. LUAD transcriptome data were retrieved from the Genotype-Tissue Expression Project (GEO) and The Cancer Genome Atlas (TCGA). Anoikis-related prognostic genes (ANRGs) were primarily screened by univariate Cox regression. All ANRGs were included in the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model to construct the powerful prognostic signature. This signature was validated and assessed using the Kaplan-Meier method as well as univariate and multivariate Cox regression analyses. Anoikis-related regulators of risk score were identified using a XG-boost machine learning model. The expression of ITGB4 protein was examined in a ZhengZhou University (ZZU) tissue cohort by immunohistochemistry, and the potential mechanisms of action of ITGB4 in LUAD were explored by GO, KEGG, and ingenuity pathway analyses and by GSEA.
A risk score signature was constructed based on eight ANRGs, with high risk scores found to closely correlate with unfavorable clinical features. ITGB4 expression may be associated with 5-year over survival, with immunohistochemistry showed that the expression of ITGB4 was higher in LUAD than in nontumor tissues. Enrichment analysis suggested that ITGB4 may promote LUAD development by targeting E2F, MYC, and oxidative phosphorylation signaling pathways.
Our anoikis-related signature from RNA-seq data may be a novel prognostic biomarker in patients with LUAD. It may help physicians develop personalized LUAD treatments in clinical practice. Moreover, ITGB4 may affect the development of LUAD through the oxidative phosphorylation pathway.
肺腺癌（LUAD）是一种侵袭性癌症，预后极差。失巢凋亡不仅促进癌细胞从原发肿瘤部位脱离，在癌症转移中也起着重要作用。然而，迄今为止，很少有研究探讨失巢凋亡在LUAD患者预后中的作用。
从Genecards和Harmonizome平台整合了总共316个与失巢凋亡相关的基因（ANRGs）。LUAD转录组数据从基因型-组织表达项目（GEO）和癌症基因组图谱（TCGA）中检索。通过单变量Cox回归初步筛选与失巢凋亡相关的预后基因（ANRGs）。将所有ANRGs纳入最小绝对收缩和选择算子（LASSO）Cox回归模型，以构建强大的预后特征。使用Kaplan-Meier方法以及单变量和多变量Cox回归分析对该特征进行验证和评估。使用XG-boost机器学习模型识别风险评分中与失巢凋亡相关的调节因子。通过免疫组织化学检测郑州大学（ZZU）组织队列中ITGB4蛋白的表达，并通过GO、KEGG和 Ingenuity通路分析以及GSEA探索ITGB4在LUAD中的潜在作用机制。
基于8个ANRGs构建了风险评分特征，发现高风险评分与不良临床特征密切相关。ITGB4表达可能与5年总生存率相关，免疫组织化学显示LUAD中ITGB4的表达高于非肿瘤组织。富集分析表明，ITGB4可能通过靶向E2F、MYC和氧化磷酸化信号通路促进LUAD的发展。
我们从RNA-seq数据中得出的与失巢凋亡相关的特征可能是LUAD患者的一种新型预后生物标志物。它可能有助于医生在临床实践中制定个性化的LUAD治疗方案。此外，ITGB4可能通过氧化磷酸化途径影响LUAD的发展。
