阐明 S100A9 的泛肿瘤学前景:综合生物信息学和孟德尔随机分析的预后和治疗推论。
Elucidating the pan-oncologic landscape of S100A9: prognostic and therapeutic corollaries from an integrative bioinformatics and Mendelian randomization analysis.
发表日期:2024 Aug 17
作者:
Yingying Chen, Zixuan Wu, Xingxing Yi
来源:
Immunity & Ageing
摘要:
钙结合蛋白 S100A9 已成为肿瘤学中的关键生物分子角色,与多种恶性肿瘤有关。这项全面的生物信息学研究超越了传统界限,研究了 S100A9 在不同肿瘤实体中的预后和治疗潜力。利用广泛的生物信息学工具和公开的癌症基因组数据库(例如 TCGA),我们系统地检查了 S100A9 基因。我们的方法包括差异表达分析、突变负荷评估、蛋白质相互作用网络和生存分析。这个强大的计算框架提供了 S100A9 在癌症生物学中的作用的高分辨率视图。该研究仔细探索了S100A9的致癌方面,综合分析了其与各种肿瘤类型的预后、肿瘤突变负荷(TMB)、微卫星不稳定性(MSI)、DNA甲基化和免疫细胞浸润的关系。这项研究呈现了一系列人类癌症中 S100A9 表达的全景图,揭示了异质表达景观。在 BLCA(膀胱尿路上皮癌)、CESC(宫颈鳞状细胞癌和宫颈内膜腺癌)、COAD(结肠腺癌)、ESCA(食管癌)和 GBM(多形性胶质母细胞瘤)等恶性肿瘤中检测到 S100A9 表达升高,而在常见于 BRCA(乳腺癌)、HNSC(头颈鳞状细胞癌)和 KICH(肾嫌色症)。这种不同的表达模式表明 S100A9 在癌症生物学中的作用是多方面的且依赖于背景。从预后来看,S100A9 表达与不同癌症类型的患者预后存在不同的相关性。此外,其表达与九种癌症类型中的 TMB 和 MSI 密切相关。六种选定肿瘤的详细检查——BRCA、CESC、KIRC(肾透明细胞癌)、LUSC(肺鳞状细胞癌)、SKCM(皮肤黑色素瘤); STAD(胃腺癌)——显示 S100A9 表达与大多数免疫细胞的浸润呈负相关,但与中性粒细胞、M1 巨噬细胞和活化 NK 细胞呈正相关,凸显了 S100A9 与肿瘤免疫环境之间复杂的相互作用。这一生物信息学综合表明 S100A9 在癌症进展中发挥着重要作用,提供了宝贵的预后见解。这些数据强调了 S100A9 作为预后生物标志物的实用性及其作为治疗靶点的潜力。其治疗意义是深远的,表明 S100A9 活性的调节可能会显着影响癌症管理策略。© 2024。作者。
The calcium-binding protein S100A9 has emerged as a pivotal biomolecular actor in oncology, implicated in numerous malignancies. This comprehensive bioinformatics study transcends traditional boundaries, investigating the prognostic and therapeutic potential of S100A9 across diverse neoplastic entities. Leveraging a wide array of bioinformatics tools and publicly available cancer genomics databases, such as TCGA, we systematically examined the S100A9 gene. Our approach included differential expression analysis, mutational burden assessment, protein interaction networks, and survival analysis. This robust computational framework provided a high-resolution view of S100A9's role in cancer biology. The study meticulously explored S100A9's oncogenic facets, incorporating comprehensive analyses of its relationship with prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), DNA methylation, and immune cell infiltration across various tumor types. This study presents a panoramic view of S100A9 expression across a spectrum of human cancers, revealing a heterogeneous expression landscape. Elevated S100A9 expression was detected in malignancies such as BLCA (Bladder Urothelial Carcinoma), CESC (Cervical squamous cell carcinoma and endocervical adenocarcinoma), COAD (Colon adenocarcinoma), ESCA (Esophageal carcinoma), and GBM (Glioblastoma multiforme), while reduced expression was noted in BRCA (Breast invasive carcinoma), HNSC (Head and Neck squamous cell carcinoma), and KICH (Kidney Chromophobe). This disparate expression pattern suggests that S100A9's role in cancer biology is multifaceted and context-dependent. Prognostically, S100A9 expression correlates variably with patient outcomes across different cancer types. Furthermore, its expression is intricately associated with TMB and MSI in nine cancer types. Detailed examination of six selected tumors-BRCA, CESC, KIRC (Kidney renal clear cell carcinoma), LUSC (Lung squamous cell carcinoma), SKCM (Skin Cutaneous Melanoma); STAD (Stomach adenocarcinoma)-revealed a negative correlation of S100A9 expression with the infiltration of most immune cells, but a positive correlation with neutrophils, M1 macrophages, and activated NK cells, highlighting the complex interplay between S100A9 and the tumor immune environment. This bioinformatics synthesis posits S100A9 as a significant player in cancer progression, offering valuable prognostic insights. The data underscore the utility of S100A9 as a prognostic biomarker and its potential as a therapeutic target. The therapeutic implications are profound, suggesting that modulation of S100A9 activity could significantly impact cancer management strategies.© 2024. The Author(s).