Wu Zuotao, Zhuo Ting, Li Zihao, Zhu Yongjie, Wu Jiejing, Liang Guanbiao, Dai Lei, Wang Yongyong, Tan Xiang, Chen Mingwu
Department of Cardio-Thoracic Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
J Cancer. 2023 Jul 24;14(12):2301-2314. doi: 10.7150/jca.86285. eCollection 2023.
Shugoshin 2 (SGO2), a component of the cell division cohesion complex, is involved in both mitotic and meiotic processes. Despite being overexpressed in various malignant tumors and is associated with poor prognosis, its exact role in lung adenocarcinoma (LUAD) and its biological effects on lung cancer cells are not well understood. The transcriptomics data and clinical information for LUAD were obtained from TCGA and GEO, and DEGs associated with prognostic risk factors were screened using Cox regression analysis and chi-square testing. Identify these gene functions using correlation heatmaps, protein interaction networks (PPIs), and KEGG enrichment assays. The expression of SGO2 in tissues was verified by PCR and IHC, and the prognostic value of SGO2 in LUAD was evaluated by survival analysis. In addition, the effects of SGO2 knockdown on lung cancer cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition (EMT) were studied in vitro. After that, the TIMER database and single-sample GSEA (ssGSEA) analysis were used to investigate the correlation between SGO2 and immune infiltration. Finally, the tumor mutational burden (TMB) of different SGO2 clusters and the efficacy of the two clusters in multiple treatments were evaluated. High-risk genes associated with poor prognosis in LUAD are involved in cell cycle regulation and proliferation. Among these genes, SGO2 exhibited high expression in LUAD and corresponded with the TNM stage. Furthermore, the knockdown of SGO2 led to a decrease in the proliferation, migration, invasion, and EMT processes of lung cancer cells. Notably, high SGO2 expression may have poorer anti-tumor immunity and may therefore be more suitable for immunotherapy to re-establish immune function, while its high expression with a higher TMB could enable LUAD to benefit from multiple therapies. Our findings suggest that SGO2 may be a promising prognostic biomarker for LUAD, particularly in regulating the cell cycle and benefiting from multiple therapies.
Shugoshin 2(SGO2)是细胞分裂黏连复合体的一个组成部分,参与有丝分裂和减数分裂过程。尽管它在各种恶性肿瘤中过度表达且与预后不良相关,但其在肺腺癌(LUAD)中的具体作用及其对肺癌细胞的生物学影响尚不清楚。从TCGA和GEO获取LUAD的转录组学数据和临床信息,并使用Cox回归分析和卡方检验筛选与预后危险因素相关的差异表达基因(DEGs)。利用相关热图、蛋白质相互作用网络(PPI)和KEGG富集分析来确定这些基因的功能。通过PCR和免疫组化(IHC)验证SGO2在组织中的表达,并通过生存分析评估SGO2在LUAD中的预后价值。此外,在体外研究了SGO2敲低对肺癌细胞增殖、迁移、侵袭和上皮-间质转化(EMT)的影响。之后,使用TIMER数据库和单样本基因集富集分析(ssGSEA)来研究SGO2与免疫浸润之间的相关性。最后,评估不同SGO2簇的肿瘤突变负荷(TMB)以及这两个簇在多种治疗中的疗效。与LUAD预后不良相关的高危基因参与细胞周期调控和增殖。在这些基因中,SGO2在LUAD中高表达且与TNM分期相关。此外,SGO2的敲低导致肺癌细胞的增殖、迁移、侵袭和EMT过程减少。值得注意的是,SGO2高表达可能具有较差的抗肿瘤免疫力,因此可能更适合免疫治疗以重建免疫功能,而其高表达且TMB较高可能使LUAD从多种治疗中获益。我们的研究结果表明,SGO2可能是LUAD一个有前景的预后生物标志物,特别是在调节细胞周期和从多种治疗中获益方面。