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整合多组学和加权网络方法揭示了 RPS7 在肺鳞癌发病机制中的预后作用。

Integrative multiomics and weighted network approach reveals the prognostic role of RPS7 in lung squamous cell carcinoma pathogenesis.

机构信息

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India.

Translational Research Lab, Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi, 110025, India.

出版信息

J Appl Genet. 2023 Dec;64(4):737-748. doi: 10.1007/s13353-023-00782-8. Epub 2023 Sep 1.

Abstract

Lung cancer is one of the most commonly occurring malignant cancers with the highest rate of mortality globally. Difference between lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) and their treatment strategies according to genetic markers may be helpful in reducing the cancer progression and increasing the overall survival (OS) in patients. LUSC is known for comparatively less typical onco-drivers, target therapy resistance, marked genomic complexity, and a reasonably higher mutation rate. The mRNA-seq data and clinical information of LUAD and LUSC cohorts from UCSC Xena comprising 437 and 379 patient samples were extracted. Differential expression and weighted network analyses revealed 47 and 18 hub differentially expressed genes (DEGs) corresponding to LUAD and LUSC cohorts. These hub DEGs were further subjected to protein-protein interaction network (PPIN) and OS analyses. Lower mRNA expression levels of both RPS15A and RPS7 worsened the OS of LUSC patients. Additionally, both these prognostic biomarkers were validated via external sources such as UALCAN, cBioPortal, TIMER, and HPA. RPS7 had higher mutation frequency compared to RPS15A and showed significant negative correlations with infiltrating levels of CD4 T cells, CD8 T cells, neutrophils, and macrophages. Our findings provided novel insights into biomarker discovery and the critical role of ribosomal biogenesis especially smaller ribosomal subunit in pathogenesis of LUSC.

摘要

肺癌是最常见的恶性肿瘤之一,在全球范围内死亡率最高。肺鳞状细胞癌(LUSC)和肺腺癌(LUAD)之间的差异及其根据遗传标志物的治疗策略可能有助于减少癌症进展并提高患者的总生存率(OS)。LUSC 的特点是相对较少的典型致癌驱动基因、靶向治疗耐药性、明显的基因组复杂性和相当高的突变率。从 UCSC Xena 中提取了包含 437 个和 379 个患者样本的 LUAD 和 LUSC 队列的 mRNA-seq 数据和临床信息。差异表达和加权网络分析揭示了对应于 LUAD 和 LUSC 队列的 47 个和 18 个枢纽差异表达基因(DEGs)。这些枢纽 DEGs 进一步进行了蛋白质-蛋白质相互作用网络(PPIN)和 OS 分析。RPS15A 和 RPS7 的 mRNA 表达水平较低会使 LUSC 患者的 OS 恶化。此外,这两个预后生物标志物通过 UALCAN、cBioPortal、TIMER 和 HPA 等外部来源进行了验证。与 RPS15A 相比,RPS7 的突变频率更高,并且与 CD4 T 细胞、CD8 T 细胞、中性粒细胞和巨噬细胞的浸润水平呈显著负相关。我们的研究结果为生物标志物发现和核糖体生物发生特别是较小的核糖体亚基在 LUSC 发病机制中的关键作用提供了新的见解。

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