HS6ST2 的泛癌分析:与预后、肿瘤免疫和耐药性的关联。
Pan-cancer analysis of HS6ST2: associations with prognosis, tumor immunity, and drug resistance.
发表日期:2024
作者:
Luxin Huang, Sidra Irshad, Ulfat Sultana, Saqib Ali, Ayesha Jamil, Ayesha Zubair, Rizwana Sultan, Mostafa A Abdel-Maksoud, Ayman Mubarak, Bandar M Almunqedhi, Taghreed N Almanaa, Abdul Malik, Abdulaziz Alamri, Ahmad S Kodous, Mohammed Mares, Mohamed Y Zaky, Syeda Saba Sajjad, Yasir Hameed
来源:
Experimental Hematology & Oncology
摘要:
在这项涵盖 33 种恶性肿瘤的综合研究中,我们探讨了硫酸乙酰肝素 6-O-磺基转移酶 2 (HS6ST2) 的差异表达和预后意义。TIMER2、UALCAN 和 GEPIA2 用于表达分析。 cBioPortal 用于突变分析。 CancerSEA、STRING 和 DAVID 分别用于单细胞测序数据分析、蛋白质-蛋白质相互作用网络开发和基因富集分析。采用GSCAlite和RT-qPCR进行药物敏感性和表达验证分析。HS6ST2在多种癌症中表现出显着(P < 0.05)过表达。从预后来看,HS6ST2 表达升高与宫颈鳞状细胞癌 (CESC)、肾嫌色细胞 (KICH)、肺腺癌 (LUAD) 和胃腺癌 (STAD) 患者的总生存期 (OS) 较差显着相关,强调了其作为癌症治疗的潜力。这些癌症的预后指标。此外,HS6ST2 表达与 CESC、KICH、LUAD 和 STAD 患者的病理阶段相关。使用 cBioPortal 对遗传改变的探索揭示了不同的突变景观,CESC、KICH、LUAD 和 STAD 中的突变频率较低。此外,CESC、KICH、LUAD 和 STAD 中 DNA 甲基化的减少表明低甲基化与 HS6ST2 表达升高之间存在潜在联系。免疫细胞浸润分析显示,CESC、KICH、LUAD 和 STAD 中 HS6ST2 表达与 CD8 T 和 CD4 T 细胞浸润呈正相关,强调了其参与肿瘤免疫过程。单细胞功能状态分析证明了 HS6ST2 与多种细胞过程之间的关联。此外,基因富集分析揭示了 HS6ST2 参与关键的细胞活动。 GSCAlite 分析强调了 HS6ST2 作为治疗靶点的潜力,显示出与药物敏感性的相关性。最后,通过逆转录定量聚合酶链反应(RT-qPCR)和免疫组织化学在 LUAD 组织中进行的实验验证证实了 HS6ST2 表达升高。总体而言,本研究提供了对 CESC、KICH、LUAD 和 STAD 中 HS6ST2 的全面了解,强调了其潜力作为预后生物标志物和治疗靶点。AJTR 版权所有 © 2024。
In this comprehensive study spanning 33 malignancies, we explored the differential expression and prognostic significance of Heparan sulfate 6-O-sulfotransferase 2 (HS6ST2).TIMER2, UALCAN, and GEPIA2 were used for the expression analysis. cBioPortal was used for mutational analysis. CancerSEA, STRING, and DAVID, were employed for the single cell sequencing data analysis, protein-protein interaction network development, and gene enrichment analyses, respectively. GSCAlite and RT-qPCR were used for drug sensitivity and expression validation analysis.HS6ST2 exhibited significant (P < 0.05) overexpression in multiple cancers. Prognostically, elevated HS6ST2 expression was significantly associated with poor overall survival (OS) in patients with cervical squamous cell carcinoma (CESC), kidney chromophobe (KICH), lung adenocarcinoma (LUAD), and stomach adenocarcinoma (STAD), emphasizing its potential as a prognostic indicator in these cancers. Moreover, HS6ST2 expression correlated with pathological stages in CESC, KICH, LUAD, and STAD patients. Exploration of genetic alterations using cBioPortal unveiled distinct mutational landscapes, with low mutation frequencies in CESC, KICH, LUAD, and STAD. Additionally, reduced DNA methylation in CESC, KICH, LUAD, and STAD suggested a potential link between hypomethylation and heightened HS6ST2 expression. Analysis of immune cell infiltration revealed a positive correlation between HS6ST2 expression and the infiltration of CD8+ T and CD4+ T cells in CESC, KICH, LUAD, and STAD, highlighting its involvement in the tumor immunology processes. Single-cell functional states analysis demonstrated associations between HS6ST2 and diverse cellular processes. Moreover, gene enrichment analysis revealed the involvement HS6ST2 in crucial cellular activities. GSCAlite analysis underscored the potential of HS6ST2 as a therapeutic target, showing associations with drug sensitivity. Finally, experimental validation through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry in LUAD tissues confirmed elevated HS6ST2 expression.Overall, this study provides a comprehensive understanding of HS6ST2 in CESC, KICH, LUAD, and STAD, emphasizing its potential as a prognostic biomarker and therapeutic target.AJTR Copyright © 2024.