Unveiling clinical significance and tumor immune landscape of CXCL12 in bladder cancer: Insights from multiple omics analysis.

IF 7 2区 医学 Q1 ONCOLOGY
Zhouting Tuo, Dechao Feng, Zhiwei Jiang, Liangkuan Bi, Chao Yang, Qi Wang
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Abstract

Objective: The interplay between chemokine C-X-C motif ligand 12 (CXCL12) and its specific receptors is known to trigger various signaling pathways, contributing to tumor proliferation and metastasis. Consequently, targeting this signaling axis has emerged as a potential strategy in cancer therapy. However, the precise role of CXCL12 in clinical therapy, especially in immunotherapy for bladder cancer (BCa), remains poorly elucidated.

Methods: We gathered multiple omics data from public databases to unveil the clinical relevance and tumor immune landscape associated with CXCL12 in BCa patients. Univariate and multivariate Cox regression analyses were employed to assess the independent prognostic significance of CXCL12 expression and formulate a nomogram. The expression of CXCL12 in BCa cell lines and clinical tissue samples was validated using enzyme-linked immunosorbent assays (ELISA) and immunohistochemistry (IHC).

Results: While transcriptional expression of CXCL12 exhibited a decrease in nearly all tumor tissues, CXCL12 methylation expression was notably increased in BCa tissues. Single-cell RNA analysis highlighted tissue stem cells and endothelial cells as the primary sources expressing CXCL12. Abnormal CXCL12 expression, based on transcriptional and methylation levels, correlated with various clinical characteristics in BCa patients. Functional analysis indicated enrichment of CXCL12 and its co-expression genes in immune regulation and cell adhesion. The immune landscape analysis unveiled a significant association between CXCL12 expression and M2 macrophages (CD163+ cells) in BCa tissues. Notably, CXCL12 expression emerged as a potential predictor of immunotherapy response and chemotherapy drug sensitivity in BCa patients.

Conclusions: Taken together, these findings suggest aberrant production of CXCL12 in BCa tissues, potentially influencing the treatment responses of affected individuals.

揭示 CXCL12 在膀胱癌中的临床意义和肿瘤免疫格局:多重全息分析的启示
研究目的众所周知,趋化因子 C-X-C motif 配体 12(CXCL12)与其特异性受体之间的相互作用会触发各种信号通路,导致肿瘤增殖和转移。因此,靶向这一信号轴已成为一种潜在的癌症治疗策略。然而,CXCL12在临床治疗中的确切作用,尤其是在膀胱癌(BCa)免疫治疗中的作用,仍未得到充分阐明:我们从公共数据库中收集了多种omics数据,以揭示CXCL12在BCa患者中的临床相关性和肿瘤免疫格局。我们采用单变量和多变量Cox回归分析来评估CXCL12表达的独立预后意义,并制定了一个提名图。使用酶联免疫吸附试验(ELISA)和免疫组织化学(IHC)验证了CXCL12在BCa细胞系和临床组织样本中的表达:结果:虽然几乎所有肿瘤组织中CXCL12的转录表达都有所下降,但BCa组织中CXCL12的甲基化表达却明显增加。单细胞 RNA 分析显示,组织干细胞和内皮细胞是表达 CXCL12 的主要来源。基于转录和甲基化水平的CXCL12异常表达与BCa患者的各种临床特征相关。功能分析表明,CXCL12及其共表达基因在免疫调节和细胞粘附方面具有富集性。免疫景观分析揭示了 BCa 组织中 CXCL12 表达与 M2 巨噬细胞(CD163+ 细胞)之间的显著关联。值得注意的是,CXCL12的表达是预测BCa患者免疫治疗反应和化疗药物敏感性的潜在指标:综上所述,这些研究结果表明,BCa组织中CXCL12的异常产生可能会影响患者的治疗反应。
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来源期刊
自引率
9.80%
发文量
1726
审稿时长
4.5 months
期刊介绍: Chinese Journal of Cancer Research (CJCR; Print ISSN: 1000-9604; Online ISSN:1993-0631) is published by AME Publishing Company in association with Chinese Anti-Cancer Association.It was launched in March 1995 as a quarterly publication and is now published bi-monthly since February 2013. CJCR is published bi-monthly in English, and is an international journal devoted to the life sciences and medical sciences. It publishes peer-reviewed original articles of basic investigations and clinical observations, reviews and brief communications providing a forum for the recent experimental and clinical advances in cancer research. This journal is indexed in Science Citation Index Expanded (SCIE), PubMed/PubMed Central (PMC), Scopus, SciSearch, Chemistry Abstracts (CA), the Excerpta Medica/EMBASE, Chinainfo, CNKI, CSCI, etc.
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