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C-X-C 趋化因子配体 3 在结肠癌患者中的诊断和预后价值。

Diagnostic and prognostic values of C‑X‑C motif chemokine ligand 3 in patients with colon cancer.

机构信息

Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.

出版信息

Oncol Rep. 2019 Nov;42(5):1996-2008. doi: 10.3892/or.2019.7326. Epub 2019 Sep 19.

Abstract

The diagnostic and prognostic mechanisms of C‑X‑C motif chemokine ligand 3 (CXCL3) in colon cancer (CC) have not yet been reported. Therefore, the objective of the present study was to use cohorts of patients from Guangxi Medical University and the Gene Expression Omnibus (GEO) database to investigate and validate CXCL3 for the diagnosis and prognosis of CC, and to explore its prospective molecular mechanism. Reverse transcription‑quantitative PCR (RT‑qPCR) analysis of 38 paired tumor and non‑tumor tissues, and immunohistochemistry (IHC) of 212 tumor and 46 non‑tumor tissues was conducted to explore the expression of CXCL3 and its diagnostic and prognostic significance in the Guangxi Medical University CC cohort. A GEO dataset, GSE40967, was used to validate the prognostic significance of CXCL3. Gene set enrichment analysis (GSEA) was also conducted to explore the potential molecular mechanisms underlying the effects of CXCL3 in CC. The RT‑qPCR results indicated that CXCL3 expression was significantly higher in cancer tissues compared with adjacent normal tissues, suggesting that it may have high diagnostic value for CC. Multivariate Cox analysis based on the IHC results suggested that there was no appreciable association between CXCL3 positivity and the overall survival (OS) time of CC. However, a stratified analysis revealed that high expression of CXCL3 was associated with considerably increased mortality in the subgroup of CC patients with tumor size <5 cm (adjusted P=0.042, adjusted HR=2.298, 95% CI=1.030‑5.126) and with tumor thrombus (adjusted P=0.019, adjusted HR=5.096, 95% CI=1.306‑19.886). In the GSE40967 dataset, high expression of CXCL3 was closely associated with poor OS in CC (adjusted P=0.049, adjusted HR=1.416, 95% CI=1.002‑2.003). Furthermore, GSEA indicated that the high expression of CXCL3 was closely associated with DNA repair, cell cycle process, cell apoptosis process and the P53 regulation pathway. In summary, these result suggest that CXCL3 might serve as a novel biomarker in the diagnosis and prognosis of CC.

摘要

CXCL3 在结肠癌(CC)中的诊断和预后机制尚不清楚。因此,本研究的目的是使用广西医科大学和基因表达综合数据库(GEO)队列的患者来研究和验证 CXCL3 在 CC 的诊断和预后中的作用,并探讨其潜在的分子机制。通过逆转录定量 PCR(RT-qPCR)分析 38 对肿瘤和非肿瘤组织,以及免疫组织化学(IHC)分析 212 例肿瘤和 46 例非肿瘤组织,探讨 CXCL3 在广西医科大学 CC 队列中的表达及其诊断和预后意义。使用 GEO 数据集 GSE40967 验证 CXCL3 的预后意义。还进行了基因集富集分析(GSEA)以探讨 CXCL3 在 CC 中作用的潜在分子机制。RT-qPCR 结果表明,与相邻正常组织相比,癌症组织中 CXCL3 的表达显著升高,提示其对 CC 具有较高的诊断价值。基于 IHC 结果的多变量 Cox 分析表明,CXCL3 阳性与 CC 患者的总生存期(OS)之间没有明显的相关性。然而,分层分析显示,在肿瘤大小<5cm(调整 P=0.042,调整 HR=2.298,95%CI=1.030-5.126)和有肿瘤栓子的 CC 患者亚组中,CXCL3 的高表达与死亡率显著增加相关(调整 P=0.019,调整 HR=5.096,95%CI=1.306-19.886)。在 GSE40967 数据集,CXCL3 的高表达与 CC 的不良 OS 密切相关(调整 P=0.049,调整 HR=1.416,95%CI=1.002-2.003)。此外,GSEA 表明,CXCL3 的高表达与 DNA 修复、细胞周期过程、细胞凋亡过程和 P53 调节途径密切相关。综上所述,这些结果表明,CXCL3 可能作为 CC 诊断和预后的新生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8a6/6787997/c9c7b735acd5/or-42-05-1996-g01.jpg

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