关键词: Kidney cancer The Cancer Genome Atlas (TCGA) clear cell carcinoma matrix metalloproteinase 14 (MMP14) prognosis

来  源:   DOI:10.21037/tau-22-619   PDF(Pubmed)

Abstract:
UNASSIGNED: Matrix metalloproteinase 14 (MMP14) has been reported to be upregulated in some types of cancer and to promote cancer cell invasion and metastasis. However, the expression profile and functional role of MMP14 in kidney renal clear cell carcinoma (KIRC) remains unknown. This study investigated the association between MMP14 expression level and prognosis in KIRC.
UNASSIGNED: The messenger RNA (mRNA) expression profile and clinical data (including T stage, N stage, M stage, pathologic stage, gender, race, age, histologic grade, serum calcium, hemoglobin) were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database. Protein expression was evaluated by immunohistochemistry in the Human Protein Atlas (HPA) database. Correlation analyses between MMP14 and all mRNAs in KIRC were batch calculated, and gene set enrichment analyses (GSEA) were then conducted of Disease Ontology (DO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using R packages. Multivariate logistic regression analysis was used to explore the prognostic factors of KIRC patients.
UNASSIGNED: The gene expression of MMP14 was significantly upregulated in KIRC tissues when compared with the normal tissue (P<0.001). The predictive ability of MMP14 as a variable for predicting tumor and normal outcomes had certain accuracy based on the receiver operating characteristic (ROC) model [area under the curve (AUC) =0.881, confidence interval (CI): 0.844-0.917]. When compared with the normal kidney tissue, the protein expression of MMP14 in KIRC got an increased trend, but due to the limited sample size, the difference is not statistically significant (P>0.05). Survival analysis revealed that MMP14 was significantly associated with overall survival in KIRC (P=0.013). GSEA of DO terms indicated high expression of MMP14 was related to KIRC, and GSEA of KEGG pathways showed that MMP14 and its coexpressed genes were significantly positively correlated with pathways in cancer. Signaling pathway GSEA indicated the upregulation of MMP14 in KIRC may activate cancer pathways.
UNASSIGNED: MMP14 may be associated with poor prognosis in KIRC and may be a potential prognostic marker for KIRC.
摘要:
未经证实:据报道,基质金属蛋白酶14(MMP14)在某些类型的癌症中上调,并促进癌细胞的侵袭和转移。然而,MMP14在肾透明细胞癌(KIRC)中的表达谱和功能作用尚不清楚.这项研究调查了KIRC中MMP14表达水平与预后之间的关系。
UNASSIGNED:信使RNA(mRNA)表达谱和临床数据(包括T期,N级,M阶段,病理阶段,性别,种族,年龄,组织学分级,血清钙,血红蛋白)从癌症基因组图谱(TCGA)和基因型组织表达(GTEx)数据库获得。通过人蛋白质图谱(HPA)数据库中的免疫组织化学评估蛋白质表达。MMP14与KIRC中所有mRNA的相关性分析进行了批量计算,然后使用R包对疾病本体论(DO)术语和京都基因和基因组百科全书(KEGG)途径进行基因集富集分析(GSEA)。采用多因素logistic回归分析探讨KIRC患者的预后因素。
未经证实:与正常组织相比,KIRC组织中MMP14的基因表达明显上调(P<0.001)。根据受试者工作特征(ROC)模型[曲线下面积(AUC)=0.881,置信区间(CI):0.844-0.917],MMP14作为预测肿瘤和正常结局的变量的预测能力具有一定的准确性。与正常肾组织相比,MMP14蛋白在KIRC中的表达有增加的趋势,但由于样本量有限,差异无统计学意义(P>0.05)。生存分析显示,MMP14与KIRC患者的总生存率显著相关(P=0.013)。DO术语的GSEA表明MMP14的高表达与KIRC有关,KEGG通路和GSEA显示MMP14及其共表达基因与肿瘤通路呈显著正相关。信号通路GSEA提示KIRC中MMP14的上调可能激活肿瘤通路。
UNASSIGNED:MMP14可能与KIRC的不良预后相关,并且可能是KIRC的潜在预后标志物。
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