Hu Hanjie, Umair Muhammad, Khan Sikandar Ali, Sani Aliya Irshad, Iqbal Sahar, Khalid Fatima, Sultan Rizwana, Abdel-Maksoud Mostafa A, Mubarak Ayman, Dawoud Turki M, Malik Abdul, Saleh Ibrahim A, Al Amri Abdul Aziz, Algarzae Norah Khaled, Kodous Ahmad S, Hameed Yasir
Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021, China.
Department of Physiology, Gomal Medical College, MTI Dera Ismail Khan, Pakistan.
Am J Transl Res. 2024 Feb 15;16(2):432-445. doi: 10.62347/WSEF7878. eCollection 2024.
Human cell division cycle-associated protein 8 (CDCA8), a critical regulator of mitosis, has been identified as a prospective prognostic biomarker in several cancer types, including breast, colon, and lung cancers. This study analyzed the diagnostic/prognostic potential and clinical implications of CDCA8 across diverse cancers.
Bioinformatics and molecular experiments.
Analyzing TCGA data via TIMER2 and GEPIA2 databases revealed significant up-regulation of CDCA8 in 23 cancer types compared to normal tissues. Prognostically, elevated CDCA8 expression correlated with poorer overall survival in KIRC, LUAD, and SKCM, emphasizing its potential as a prognostic marker. UALCAN analysis demonstrated CDCA8 up-regulation based on clinical variables, such as cancer stage, race, and gender, in these cancers. Epigenetic exploration indicated reduced CDCA8 promoter methylation levels in Kidney Renal Clear Cell Carcinoma (KIRC), Lung Adenocarcinoma (LUAD), and Skin Cutaneous Melanoma (SKCM) tissues compared to normal controls. Promoter methylation and mutational analyses showcased a hypomethylation and low mutation rate for CDCA8 in these cancers. Correlation analysis revealed positive associations between CDCA8 expression and infiltrating immune cells, particularly CD8+ and CD4+ T cells. Protein-protein interaction (PPI) network analysis unveiled key interacting proteins, while gene enrichment analysis highlighted their involvement in crucial cellular processes and pathways. Additionally, exploration of CDCA8-associated drugs through DrugBank presented potential therapeutic options for KIRC, LUAD, and SKCM. In vitro validation using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) confirmed elevated CDCA8 expression in LUAD cell lines (A549 and H1299) compared to control cell lines (Beas-2B and NL-20).
This study provides concise insights into CDCA8's multifaceted role in KIRC, LUAD, and SKCM, covering expression patterns, diagnostic and prognostic relevance, epigenetic regulation, mutational landscape, immune infiltration, and therapeutic implications.
人类细胞分裂周期相关蛋白8（CDCA8）是有丝分裂的关键调节因子，已被确定为包括乳腺癌、结肠癌和肺癌在内的多种癌症类型中的一种潜在预后生物标志物。本研究分析了CDCA8在多种癌症中的诊断/预后潜力及临床意义。
生物信息学和分子实验。
通过TIMER2和GEPIA2数据库分析TCGA数据显示，与正常组织相比，23种癌症类型中CDCA8显著上调。在预后方面，CDCA8表达升高与肾透明细胞癌（KIRC）、肺腺癌（LUAD）和皮肤黑色素瘤（SKCM）的总体生存率较差相关，强调了其作为预后标志物的潜力。UALCAN分析表明，在这些癌症中，基于癌症分期、种族和性别等临床变量，CDCA8表达上调。表观遗传学研究表明，与正常对照相比，肾透明细胞癌（KIRC）、肺腺癌（LUAD）和皮肤黑色素瘤（SKCM）组织中CDCA8启动子甲基化水平降低。启动子甲基化和突变分析显示，这些癌症中CDCA8存在低甲基化和低突变率。相关性分析揭示了CDCA8表达与浸润性免疫细胞，特别是CD8 +和CD4 + T细胞之间的正相关。蛋白质-蛋白质相互作用（PPI）网络分析揭示了关键的相互作用蛋白，而基因富集分析突出了它们参与关键细胞过程和途径。此外，通过DrugBank探索CDCA8相关药物为KIRC、LUAD和SKCM提供了潜在的治疗选择。使用逆转录定量聚合酶链反应（RT-qPCR）进行的体外验证证实，与对照细胞系（Beas-2B和NL-20）相比，LUAD细胞系（A549和H1299）中CDCA8表达升高。
本研究对CDCA8在KIRC、LUAD和SKCM中的多方面作用提供了简要见解，涵盖表达模式、诊断和预后相关性、表观遗传调控、突变格局、免疫浸润和治疗意义。
