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SPECC1作为一种泛癌生物标志物:揭示其在药物敏感性和耐药机制中的作用

SPECC1 as a pan-cancer biomarker: unraveling its role in drug sensitivity and resistance mechanisms.

作者信息

Liu Dongwei, Wang Xidi, Cui Lingfei, Zhang Mingxia, Lei Kefeng, Aierken Nijiati

机构信息

Department of General Practice, The seventh Affiliated Hospital of sun yat-sen university, Shenzhen, 518107, China.

Department of Thyroid and Breast surgery, The seventh Affiliated Hospital of sun yat-sen university, Shenzhen, 518107, China.

出版信息

Discov Oncol. 2024 Oct 13;15(1):552. doi: 10.1007/s12672-024-01426-x.

DOI:10.1007/s12672-024-01426-x
PMID:39397181
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11471742/
Abstract

Previous studies have shown a relationship between SPECC1 and the prognosis of breast cancer, indicating a potential function for SPECC1 in the initiation and progression of cancer. However, the role played by SPECC1 in other tumors is not yet known. Therefore, we used bioinformatics techniques to conduct a thorough investigation into the possible mechanism of SPECC1 in pan-cancer, analyzing data reported in the literature as well as databases such as GTEx and CCLE, cBioportal, TCGA, and UCSC XENA. Comparing the results with matching normal tissues, the majority of cancers, including pancreatic adenocarcinoma (PAAD) and breast invasive carcinoma (BRCA), exhibited higher levels of SPECC1, while hepatocellular carcinoma (HCC) showed lower expression levels. SPECC1 was also found to be genetically mutated in endometrial cancer, sarcoma, and esophageal cancer. The prognosis of lung adenocarcinoma, kidney papillary cell carcinoma, and breast cancer is highly correlated with dysregulation of SPECC1 expression. This work helps guide clinical therapy by highlighting the sensitivity of tumor-treating medicines and the prognostic importance of SPECC1 in various malignancies. KEGG pathway enrichment analysis revealed focused adhesion, collagen-containing extracellular matrix (collagen), and the primary enrichment domains for SPECC1-related genes. These findings were obtained through gene annotation (GO) examination of SPECC1 expression. Primary mediators of the cytokine-cytokine receptor interaction include PICOC1-associated genes, cell-substrate junction genes, and extracellular matrix containing collagen. PICOC1-associated genes primarily mediate the PI3K-AKT signaling pathway. Drug sensitivity assay showed that SPECC1 high-expressing cell lines were more sensitive to docetaxel, doxorubicin, etc. In conclusion, the current study shows how SPECC1 is expressed in different cancers and how this expression relates to the prognosis of the tumor. It also revealed the mutations and copy number variations of SPECC1 in various tumors and its potential involvement in cellular pathway regulatory networks and cytological processes. This study examines the relationship between immune genes, cellular infiltration, and immunological scores in the tumor microenvironment, which explain the severity of the disease. This study looks at the response of SPEC1 expression to anticancer therapy. Explains the prognostic significance and drug response of SPECC-1.

摘要

先前的研究表明SPECC1与乳腺癌的预后之间存在关联,这表明SPECC1在癌症的发生和发展中具有潜在作用。然而,SPECC1在其他肿瘤中所起的作用尚不清楚。因此,我们运用生物信息学技术对SPECC1在泛癌中的可能机制进行了深入研究,分析了文献报道的数据以及GTEx、CCLE、cBioportal、TCGA和UCSC XENA等数据库。将结果与匹配的正常组织进行比较,大多数癌症,包括胰腺腺癌(PAAD)和乳腺浸润性癌(BRCA),表现出较高水平的SPECC1,而肝细胞癌(HCC)则表现出较低的表达水平。还发现SPECC1在子宫内膜癌、肉瘤和食管癌中发生基因变异。肺腺癌、肾乳头状细胞癌和乳腺癌的预后与SPECC1表达失调高度相关。这项工作通过突出肿瘤治疗药物的敏感性以及SPECC1在各种恶性肿瘤中的预后重要性,有助于指导临床治疗。KEGG通路富集分析揭示了粘着斑、含胶原蛋白的细胞外基质(胶原蛋白)以及SPECC1相关基因的主要富集结构域。这些发现是通过对SPECC1表达的基因注释(GO)检查获得的。细胞因子-细胞因子受体相互作用的主要介质包括PICOC1相关基因、细胞-底物连接基因和含胶原蛋白的细胞外基质。PICOC1相关基因主要介导PI3K-AKT信号通路。药物敏感性试验表明,高表达SPECC1的细胞系对多西他赛、阿霉素等更敏感。总之,当前的研究展示了SPECC1在不同癌症中的表达情况以及这种表达与肿瘤预后的关系。它还揭示了SPECC1在各种肿瘤中的突变和拷贝数变异及其在细胞通路调控网络和细胞学过程中的潜在参与。这项研究考察了肿瘤微环境中免疫基因、细胞浸润和免疫评分之间的关系,这解释了疾病的严重程度。这项研究观察了SPEC1表达对抗癌治疗的反应。解释了SPECC-1的预后意义和药物反应。

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