Abstract：
BACKGROUND: Cholangiocarcinoma (CCA) stands as an aggressive malignancy of the biliary tract. The interplay between the tumor and immune system plays a pivotal role in disease progression and treatment outcomes. Hence, the present study aimed to extensively explore the immunogenomic landscape of CCA, with the objective of unveiling unique molecular and immunological signatures that could guide personalized therapeutic approaches.
METHODS: The study collected data from The Cancer Genome Atlas databases, performed gene set variation analysis for the chemokine ligand 5 (CCL5) high/low expression group, conducted principal component analysis, gene set enrichment analysis enrichment and mutation pattern analysis, generated a heatmap, and performed cox regression analysis.
RESULTS: The two discrete subpopulations were found to exhibit contrasting mutational and immunogenomic characteristics, emphasizing the heterogeneity of CCA. These subsets also showed pronounced discrepancies in the infiltration of immune cells, indicating diverse interactions with the tumor immune microenvironment. Furthermore, the dissimilarities in mutational patterns were observed within the two CCA subgroups, with PBRM1 and BAP1 emerging as the most frequently mutated genes. In addition, a prognostic framework was formulated and validated utilizing the expression profiles of COX16 and RSAD2 genes, effectively segregating patients into high-risk and low-risk cohorts. Furthermore, the connections between immune-related parameters and these risk groups were identified, underscoring the potential significance of the immune microenvironment in patient prognosis. In vitro experiments have shown that COX16 promotes the proliferation and metastasis of CCA cells, whereas RSAD2 inhibits it.
CONCLUSIONS: The present study provides an intricate depiction of the immunogenomic landscape of CCA based on CCL5 expression, thereby paving the way for novel immunotherapy strategies and prognostic assessment.
METHODS: The study collected data from The Cancer Genome Atlas databases, performed gene set variation analysis for the chemokine ligand 5 (CCL5) high/low expression group, conducted principal component analysis, gene set enrichment analysis enrichment and mutation pattern analysis, generated a heatmap, and performed cox regression analysis.
RESULTS: The two discrete subpopulations were found to exhibit contrasting mutational and immunogenomic characteristics, emphasizing the heterogeneity of CCA. These subsets also showed pronounced discrepancies in the infiltration of immune cells, indicating diverse interactions with the tumor immune microenvironment. Furthermore, the dissimilarities in mutational patterns were observed within the two CCA subgroups, with PBRM1 and BAP1 emerging as the most frequently mutated genes. In addition, a prognostic framework was formulated and validated utilizing the expression profiles of COX16 and RSAD2 genes, effectively segregating patients into high-risk and low-risk cohorts. Furthermore, the connections between immune-related parameters and these risk groups were identified, underscoring the potential significance of the immune microenvironment in patient prognosis. In vitro experiments have shown that COX16 promotes the proliferation and metastasis of CCA cells, whereas RSAD2 inhibits it.
CONCLUSIONS: The present study provides an intricate depiction of the immunogenomic landscape of CCA based on CCL5 expression, thereby paving the way for novel immunotherapy strategies and prognostic assessment.
摘要：
背景：胆管癌（CCA）是一种侵袭性的胆道恶性肿瘤。肿瘤和免疫系统之间的相互作用在疾病进展和治疗结果中起关键作用。因此，本研究旨在广泛探索CCA的免疫基因组景观，目的是揭示独特的分子和免疫学特征，可以指导个性化的治疗方法。
方法：该研究从癌症基因组图谱数据库收集数据，对趋化因子配体5（CCL5）高/低表达组进行基因集变异分析，进行了主成分分析，基因集富集分析富集和突变模式分析，生成了一个热图，并进行了cox回归分析。
结果：发现两个离散的亚群表现出相反的突变和免疫基因组特征，强调CCA的异质性。这些亚群在免疫细胞的浸润方面也显示出明显的差异，表明与肿瘤免疫微环境的不同相互作用。此外，在两个CCA亚组中观察到突变模式的差异，PBRM1和BAP1是最常见的突变基因。此外,利用COX16和RSAD2基因的表达谱制定并验证了预后框架，有效地将患者分为高风险和低风险队列。此外，确定了免疫相关参数与这些风险组之间的联系，强调免疫微环境在患者预后中的潜在意义。体外实验表明，COX16促进CCA细胞的增殖和转移，而RSAD2抑制它。
结论：本研究提供了基于CCL5表达的CCA免疫基因组景观的复杂描述，从而为新的免疫治疗策略和预后评估铺平了道路。
方法：该研究从癌症基因组图谱数据库收集数据，对趋化因子配体5（CCL5）高/低表达组进行基因集变异分析，进行了主成分分析，基因集富集分析富集和突变模式分析，生成了一个热图，并进行了cox回归分析。
结果：发现两个离散的亚群表现出相反的突变和免疫基因组特征，强调CCA的异质性。这些亚群在免疫细胞的浸润方面也显示出明显的差异，表明与肿瘤免疫微环境的不同相互作用。此外，在两个CCA亚组中观察到突变模式的差异，PBRM1和BAP1是最常见的突变基因。此外,利用COX16和RSAD2基因的表达谱制定并验证了预后框架，有效地将患者分为高风险和低风险队列。此外，确定了免疫相关参数与这些风险组之间的联系，强调免疫微环境在患者预后中的潜在意义。体外实验表明，COX16促进CCA细胞的增殖和转移，而RSAD2抑制它。
结论：本研究提供了基于CCL5表达的CCA免疫基因组景观的复杂描述，从而为新的免疫治疗策略和预后评估铺平了道路。
