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综合分析确定 为结直肠癌中一种潜在的预后和免疫治疗相关生物标志物。 (注:原文中“Identifies”后缺少具体内容)

Integrated Profiling Identifies as a Potential Prognostic and Immunotherapy Relevant Biomarker in Colorectal Cancer.

作者信息

Shi Junhong, Bao Meiyu, Wang Weifeng, Wu Xuan, Li Yueying, Zhao Changdong, Liu Weiwei

机构信息

Department of Laboratory Medicine and Central Laboratory, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Department of Central Laboratory, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.

出版信息

Front Immunol. 2021 Sep 27;12:722807. doi: 10.3389/fimmu.2021.722807. eCollection 2021.

Abstract

Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 3 () is related to a variety of human diseases. However, its function in Colorectal cancer (CRC) remains uncertain. expression was analyzed using The Cancer Genome Atlas (TCGA) pan-cancer data. DAVID was used for enrichment analysis of -related genes. The correlation between expression and immune cell infiltration was evaluated. Four expression profile datasets (GSE17536, GSE39582, GSE74602, and GSE113513) from Gene Expression Omnibus, and two proteomic datasets were used as validation cohorts for assessing the diagnostic and prognostic value of in CRC. What's more, we performed immunohistochemistry (IHC) staining for PLOD3 in 160 paired CRC specimens and corresponding adjacent non-tumor tissues. was highly expressed in many tumors including CRC. was upregulated in advanced stage CRCs, and high expression was associated with poor survival. High expression was associated with low levels of B cells, CD4 T cells, M1 macrophages, CD8 T cells, and multiple immunerelated characteristics. In addition, the high expression group had a higher TIDE score and a lower tumor mutation burden and microsatellite instability, indicating that patients with high expression may be resistant to immunotherapy. Additional datasets and IHC analysis were used to validate the diagnostic and prognostic value of at the mRNA and protein levels in CRC. Patients with non-response to immunotherapy showed increased expression in an immunotherapy treated dataset. is a potential biomarker for CRC diagnosis and prognosis prediction. CRCs with high expression may be resistant to immune checkpoint therapy.

摘要

前胶原赖氨酸,2-氧戊二酸5-双加氧酶3(PLOD3)与多种人类疾病相关。然而,其在结直肠癌(CRC)中的功能仍不确定。使用癌症基因组图谱(TCGA)泛癌数据对PLOD3表达进行分析。DAVID用于对PLOD3相关基因进行富集分析。评估PLOD3表达与免疫细胞浸润之间的相关性。来自基因表达综合数据库的四个表达谱数据集(GSE17536、GSE39582、GSE74602和GSE113513)以及两个蛋白质组学数据集用作验证队列,以评估PLOD3在CRC中的诊断和预后价值。此外,我们对160对CRC标本及相应的癌旁非肿瘤组织进行了PLOD3的免疫组织化学(IHC)染色。PLOD3在包括CRC在内的许多肿瘤中高表达。在晚期CRC中PLOD3上调,高表达与较差的生存率相关。高PLOD3表达与B细胞、CD4 T细胞、M1巨噬细胞、CD8 T细胞水平低以及多种免疫相关特征相关。此外,高PLOD3表达组具有更高的TIDE评分以及更低的肿瘤突变负担和微卫星不稳定性,表明高PLOD3表达的患者可能对免疫治疗耐药。使用额外的数据集和IHC分析在mRNA和蛋白质水平验证PLOD3在CRC中的诊断和预后价值。在一个免疫治疗的数据集里,对免疫治疗无反应的患者显示PLOD3表达增加。PLOD3是CRC诊断和预后预测的潜在生物标志物。高PLOD3表达的CRC可能对免疫检查点治疗耐药。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e70b/8503557/aa201322872a/fimmu-12-722807-g001.jpg

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