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基于整合生物信息学的 hedgehog 信号在膀胱癌中的预后价值。

The prognostic value of hedgehog signaling in bladder cancer by integrated bioinformatics.

机构信息

Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.

Department of Oncology, Shanghai Artemed Hospital, Shanghai, People's Republic of China.

出版信息

Sci Rep. 2023 Apr 17;13(1):6241. doi: 10.1038/s41598-023-33140-z.

Abstract

Bladder cancer is the second most prevalent urological malignancy. It's a big contributor to cancer-related deaths throughout the globe. Researchers discovered that the hedgehog signaling (HhS) pathway contributed to the onset and spread of many different kinds of cancer. Nevertheless, the present understanding of the function of HhS in the bladder cancer molecular landscape is incomplete. Raw data were gotten from the IMvigor210, the Gene Expression Omnibus, and The Cancer Genome Atlas databases. Bioinformatics was used to examine the HhS score of each sample, and the enrichment of differentially expressed genes (DEGs), differentiation characteristics, immunological infiltration, and metabolic activity. The HhS prognostic signature was developed with significant assistance from the least absolute shrinkage and selection operator regression and Cox regression. An HhS-related nomogram was developed to assist in the prediction of patients' survival probability. We found that HhS was linked to poor prognosis in bladder cancer, and its activation was linked to the Basal subtype of bladder cancer. Bladder cancer with high HhS activity has higher glycolysis, nucleotide metabolism, amino acid metabolism, and other cancer-promoting metabolic activities. Furthermore, HhS mediates an immunosuppressive microenvironment in bladder cancer on the basis that HhS negatively correlates with the CD8 + T cells and correlates positively with immune checkpoints and T cell exhaustion scores. Finally, an HhS-related signature was developed for predicting the prognosis of patients with bladder cancer. Targeting HhS may be a potential therapy choice for bladder cancer.

摘要

膀胱癌是第二大常见的泌尿系统恶性肿瘤。它是全球癌症相关死亡的主要原因之一。研究人员发现 hedgehog 信号通路(HhS)有助于许多不同类型癌症的发生和扩散。然而,目前对 HhS 在膀胱癌分子图谱中的功能的理解还不完整。原始数据来自 IMvigor210、基因表达综合数据库和癌症基因组图谱数据库。生物信息学用于检查每个样本的 HhS 评分,以及差异表达基因(DEGs)、分化特征、免疫浸润和代谢活性的富集情况。HhS 预后特征是在最小绝对收缩和选择算子回归和 Cox 回归的显著帮助下开发的。开发了一个与 HhS 相关的列线图,以帮助预测患者的生存概率。我们发现 HhS 与膀胱癌的不良预后有关,其激活与膀胱癌的基底亚型有关。具有高 HhS 活性的膀胱癌具有更高的糖酵解、核苷酸代谢、氨基酸代谢和其他促进癌症的代谢活性。此外,HhS 在膀胱癌中介导了一种免疫抑制微环境,因为 HhS 与 CD8+T 细胞呈负相关,与免疫检查点和 T 细胞耗竭评分呈正相关。最后,开发了一个与 HhS 相关的signature 来预测膀胱癌患者的预后。靶向 HhS 可能是膀胱癌的一种潜在治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd0a/10110581/4b62297c2d68/41598_2023_33140_Fig1_HTML.jpg

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