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鉴定整合素β2(ITGB2)作为卵巢癌潜在的预后生物标志物。

Identifying ITGB2 as a Potential Prognostic Biomarker in Ovarian Cancer.

作者信息

Li Chanyuan, Deng Ting, Cao Junya, Zhou Yun, Luo Xiaolin, Feng Yanling, Huang He, Liu Jihong

机构信息

Cancer Center, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China.

Department of Gynecologic Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, China.

出版信息

Diagnostics (Basel). 2023 Mar 18;13(6):1169. doi: 10.3390/diagnostics13061169.

Abstract

Epithelial ovarian cancer is by far the most lethal gynecological malignancy. The exploration of promising immunomarkers to predict prognosis in ovarian cancer patients remains challenging. In our research, we carried out an integrated bioinformatic analysis of genome expressions and their immune characteristics in the ovarian cancer microenvironment with validation in different experiments. We filtrated 332 differentially expressed genes with 10 upregulated hub genes from the Gene Expression Omnibus database. These genes were closely related to ovarian tumorigenesis. Subsequently, the survival and immune infiltration analysis demonstrated that the upregulation of five candidate genes, ITGB2, VEGFA, CLDN4, OCLN, and SPP1, were correlated with an unfavorable clinical outcome and increased immune cell infiltration in ovarian cancer. Of these genes, ITGB2 tended to be the gene most correlated with various immune cell infiltrations and had a strong correlation with significant M2 macrophages infiltration (r = 0.707, = 4.71 × 10), while it had a moderate correlation with CD4+/CD8+ T cells and B cells. This characteristic explains why the high expression of ITGB2 was accompanied by immune activation but did not reverse carcinogenesis. Additionally, we confirmed that ITGB2 was over-expressed in ovarian cancer tissues and was mainly located in cytoplasm, detected by Western blotting and the immunohistochemical method. In summary, ITGB2 may serve as a prognostic immunomarker for ovarian cancer patients.

摘要

上皮性卵巢癌是迄今为止最致命的妇科恶性肿瘤。探索有前景的免疫标志物以预测卵巢癌患者的预后仍然具有挑战性。在我们的研究中,我们对卵巢癌微环境中的基因组表达及其免疫特征进行了综合生物信息学分析,并在不同实验中进行了验证。我们从基因表达综合数据库中筛选出332个差异表达基因,其中有10个上调的核心基因。这些基因与卵巢肿瘤发生密切相关。随后的生存和免疫浸润分析表明,五个候选基因ITGB2、VEGFA、CLDN4、OCLN和SPP1的上调与卵巢癌不良临床结局及免疫细胞浸润增加相关。在这些基因中,ITGB2往往是与各种免疫细胞浸润最相关的基因,与显著的M2巨噬细胞浸润有很强的相关性(r = 0.707,P = 4.71×10),而与CD4+/CD8+ T细胞和B细胞有中等相关性。这一特征解释了为什么ITGB2的高表达伴随着免疫激活但并未逆转致癌过程。此外,我们通过蛋白质印迹法和免疫组织化学方法证实,ITGB2在卵巢癌组织中过表达,且主要位于细胞质中。总之,ITGB2可能作为卵巢癌患者的预后免疫标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05d2/10047357/0ac3e529c1e4/diagnostics-13-01169-g001.jpg

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