Prognosis poor, immune infiltration of colon adenocarcinoma associated with low expression levels of calcium-activated chloride channel.

IF 0.7 4区 医学 Q4 PATHOLOGY Polish Journal of Pathology Pub Date : 2024-01-01 DOI:10.5114/pjp.2024.141232
Xueying Zhao, Yunfan Chen, Liyuan Wang, Dongli Sui, Jin Lu
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Abstract

The calcium-activated chloride channel (CLCA4) in colon adenocarcinoma (COAD) and immunological infiltration have not been extensively studied. This work thoroughly employed several datasets to assess the expression, prognosis, and association between immune infiltration and clinicopathological characteristics of CLCA4 in cancer, as well as look into potential signalling pathways. The human protein atlas (HPA), TIMER, UALCAN, TISIDB, GSCA, SangerBox, GeneMANIA, and LinkedOmics were among the datasets that were used. The findings demonstrated that, in comparison to normal tissues, COAD tissues had lower levels of CLCA4 expression. The prognosis was worse for those whose levels of CLCA4 expression were lower. For validation, immunohistochemistry (HPA) was used. Positive correlations between CLCA4 mRNA expression and its copy number variation (CNV) were observed, and CLCA4 CNV was linked to immunological infiltration. Subsequent investigation demonstrated the association between immune cell markers, immune checkpoint genes, and immunological infiltration with CLCA4. The overall survival and disease-free survival of M0 patients were considerably better than those of M1 patients, and the groups with tumour stages M0 and M1 had notably different levels of CLCA4 expression. Its substantial enrichment in ion channel activity, transmembrane transporter activity, digestion, and other biological processes was revealed by gene ontology analysis. Oxidative phosphorylation, pancreatic secretion, Parkinson's and Alzheimer's diseases, renin secretion, and other signalling pathways were the primary associations found for CLCA4. It is evident that the immunological microenvironment and functions like ion transport, metabolism, and intestinal digestion are all impacted by CLCA4 expression.

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预后不良,结肠腺癌的免疫浸润与钙激活氯通道的低表达水平有关。
结肠腺癌(COAD)中的钙激活氯通道(CLCA4)和免疫浸润尚未得到广泛研究。这项研究采用了多个数据集来评估 CLCA4 在癌症中的表达、预后以及免疫浸润与临床病理特征之间的关联,并研究潜在的信号通路。使用的数据集包括人类蛋白质图谱(HPA)、TIMER、UALCAN、TISIDB、GSCA、SangerBox、GeneMANIA和LinkedOmics。研究结果表明,与正常组织相比,COAD 组织的 CLCA4 表达水平较低。CLCA4表达水平较低的患者预后较差。为了进行验证,采用了免疫组化(HPA)方法。结果发现,CLCA4 mRNA表达与其拷贝数变异(CNV)呈正相关,CLCA4 CNV与免疫浸润有关。随后的研究表明,免疫细胞标记物、免疫检查点基因和免疫浸润与CLCA4之间存在关联。M0患者的总生存率和无病生存率明显优于M1患者,而肿瘤分期为M0和M1的两组患者的CLCA4表达水平明显不同。基因本体分析表明,CLCA4在离子通道活性、跨膜转运体活性、消化和其他生物过程中的表达非常丰富。氧化磷酸化、胰腺分泌、帕金森氏症和阿尔茨海默氏症、肾素分泌和其他信号通路是 CLCA4 的主要关联。显然,免疫微环境以及离子转运、新陈代谢和肠道消化等功能都会受到 CLCA4 表达的影响。
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来源期刊
CiteScore
1.00
自引率
0.00%
发文量
21
审稿时长
>12 weeks
期刊介绍: Polish Journal of Pathology is an official magazine of the Polish Association of Pathologists and the Polish Branch of the International Academy of Pathology. For the last 18 years of its presence on the market it has published more than 360 original papers and scientific reports, often quoted in reviewed foreign magazines. A new extended Scientific Board of the quarterly magazine comprises people with recognised achievements in pathomorphology and biology, including molecular biology and cytogenetics, as well as clinical oncology. Polish scientists who are working abroad and are international authorities have also been invited. Apart from presenting scientific reports, the magazine will also play a didactic and training role.
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