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COL24A1在肝细胞癌中的过表达预示不良预后:一项基于多个数据库、临床样本和细胞系的研究

Overexpression of COL24A1 in Hepatocellular Carcinoma Predicts Poor Prognosis: A Study Based on Multiple Databases, Clinical Samples and Cell Lines.

作者信息

Yan Long, Xu Feng, Dai Chaoliu

机构信息

Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Apr 2;13:2819-2832. doi: 10.2147/OTT.S247133. eCollection 2020.

Abstract

PURPOSE

Hepatocellular carcinoma (HCC) ranks as the second leading cause of cancer-related deaths worldwide and its incidence tends to increase globally. Current biomarkers can hardly reflect diagnostic significance and therapeutic efficiency accurately. The role of collagen 24A1 (COL24A1) in HCC, as a member of the collagen family, remains unclear and needs to be proved.

METHODS

HCC-associated RNA sequencing datasets were obtained from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Oncomine databases. R language was used to screen and analyze the differential expression genes (DEGs). Gene Ontology (GO) pathway analyses of DEGs were carried out using g:profiler. Then, the STRING database and cytoscape software were applied to estimate the correlations between DEGs. GEPIA and HCCDB database were used to verify and analyze these results. Finally, qPCR and immunohistochemistry staining on clinical samples and HCC cell lines were conducted to further verify the above results.

RESULTS

The expression of COL24A1 in HCC tissues was significantly higher than that in normal hepatic (NH) tissues. The analysis of TCGA and Oncomine database samples proved that COL24A1 expression was connected with tumor grade, tumor stage and pathologic stage. Meanwhile, the overall survival (OS) curve also validated that high expression of COL24A1 indicated poor prognosis. And the above results have been verified in our clinical samples and HCC cell lines. Furthermore, there is a significant increase of the expression of COL24A1 in various tumors. COL24A1, together with other interactive proteins, has a significant effect on the prognosis of HCC.

CONCLUSION

Overall, COL24A1 may be an oncogene in the development of HCC. Also, the overexpression of COL24A1 in HCC may help diagnose HCC and evaluate prognosis.

摘要

目的

肝细胞癌(HCC)是全球癌症相关死亡的第二大主要原因,其发病率在全球范围内呈上升趋势。目前的生物标志物难以准确反映诊断意义和治疗效果。作为胶原蛋白家族的一员,胶原蛋白24A1(COL24A1)在HCC中的作用仍不清楚,有待证实。

方法

从癌症基因组图谱(TCGA)、国际癌症基因组联盟(ICGC)和Oncomine数据库中获取与HCC相关的RNA测序数据集。使用R语言筛选和分析差异表达基因(DEG)。使用g:profiler对DEG进行基因本体(GO)通路分析。然后,应用STRING数据库和cytoscape软件评估DEG之间的相关性。使用GEPIA和HCCDB数据库对这些结果进行验证和分析。最后,对临床样本和HCC细胞系进行qPCR和免疫组织化学染色,以进一步验证上述结果。

结果

COL24A1在HCC组织中的表达明显高于正常肝组织(NH)。对TCGA和Oncomine数据库样本的分析证明,COL24A1表达与肿瘤分级、肿瘤分期和病理分期相关。同时,总生存(OS)曲线也证实,COL24A1高表达表明预后不良。上述结果在我们的临床样本和HCC细胞系中得到了验证。此外,COL24A1在各种肿瘤中的表达显著增加。COL24A1与其他相互作用蛋白一起,对HCC的预后有显著影响。

结论

总体而言,COL24A1可能是HCC发生发展中的一个癌基因。此外,COL24A1在HCC中的过表达可能有助于HCC的诊断和预后评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bde7/7135145/f0f32c610fe7/OTT-13-2819-g0001.jpg

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