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FAM189B 高表达与胃癌患者的预后相关。

High FAM189B Expression and Its Prognostic Value in Patients with Gastric Cancer.

机构信息

Department of Gastroenterology, Guangxi International Zhuang Medicine Hospital, Nanning, 530200 Guangxi, China.

出版信息

Biomed Res Int. 2021 May 25;2021:8875971. doi: 10.1155/2021/8875971. eCollection 2021.

Abstract

The clinical significance of the family with sequence similarity 189 member B (FAM189B) gene remains largely unknown in gastric cancer (GC). A comprehensive investigation combining multiple detection methods was carried out in the current study to unveil the clinical implications and prospective molecular characterization of FAM189B protein and mRNA in GC. The protein level of FAM189B was clearly upregulated in the tumor tissues of GC as compared to noncancerous gastric tissues with 179 GC cases and 147 noncancerous gastric controls assessed by immunohistochemistry. The upregulation of the FAM189B protein was also found in the more deteriorating period of the tumor, as there were increasing trends in the groups of larger tumors, with lymph node metastasis, a further advanced clinical stage, and a higher histological grade. Next, we focused on the mRNA level of FAM189B in GC tissues using various high-throughput data. After the screening of GEO, ArrayExpress, and SRA, we finally achieved 18 datasets, including an RNA sequencing dataset of TCGA. Altogether, 1095 cases of GC tissue samples were collected, with 305 unique examples of noncancerous controls. Concerning the mRNA level of FAM189B in GC, the final standard mean difference (SMD) was 0.46 and the area under the curve (AUC) was 0.79 for the upregulation of FAM189B mRNA, which confirmed that the FAM189B mRNA level was also markedly upregulated in GC tissues and comparable to its protein level. The survival analysis showed that the higher expression of FAM189B was a risk factor for the overall survival, first progression, and postprogression survival of GC. For the Affymetrix ID 1555515_a_at of FAM189B, the higher expression level of FAM189B predicted a lower overall survival, first progression survival, and postprogression survival with the hazard ratio (HR) being 1.56 (1.24, 1.95), 1.69 (1.32, 2.17), and 1.97 (1.5, 2.6), respectively. For the Affymetrix ID 203550_s_at of FAM189B, a similar result could be found with corresponding HR being 1.49 (1.24, 1.8), 1.49 (1.21, 1.83), and 1.66 (1.32, 2.08), respectively. The interaction of MEM, COXPRESdb coexpressed genes, and DEGs of GC finally generated 368 genes, and the pathway of the cell cycle was the top pathway enriched by KEGG. In conclusion, the overexpression of the FAM189B protein and mRNA might enhance the incidence of GC.

摘要

家族性 189 成员 B(FAM189B)基因在胃癌(GC)中的临床意义在很大程度上尚不清楚。本研究采用多种检测方法进行综合研究,揭示 FAM189B 蛋白和 mRNA 在 GC 中的临床意义和潜在的分子特征。

通过免疫组织化学方法评估了 179 例 GC 病例和 147 例非癌性胃对照组织,结果显示 FAM189B 蛋白在肿瘤组织中的表达明显上调。在肿瘤更恶化的时期也发现了 FAM189B 蛋白的上调,随着肿瘤较大、淋巴结转移、临床分期进一步进展和组织学分级较高的趋势,上调的趋势也越来越明显。

接下来,我们使用各种高通量数据集中的 FAM189B 在 GC 组织中的 mRNA 水平进行了研究。在筛选 GEO、ArrayExpress 和 SRA 后,我们最终获得了 18 个数据集,包括 TCGA 的 RNA 测序数据集。总共收集了 1095 例 GC 组织样本,其中 305 例为非癌性对照的独特样本。

关于 FAM189B 在 GC 中的 mRNA 水平,最终标准化均差(SMD)为 0.46,曲线下面积(AUC)为 0.79,表明 FAM189B mRNA 水平在 GC 组织中也明显上调,与蛋白水平相当。生存分析表明,FAM189B 的高表达是 GC 总生存、首次进展和后进展生存的危险因素。对于 FAM189B 的 Affymetrix ID 1555515_a_at,FAM189B 高表达预示着总体生存率、首次进展生存率和后进展生存率较低,风险比(HR)分别为 1.56(1.24,1.95)、1.69(1.32,2.17)和 1.97(1.5,2.6)。对于 FAM189B 的 Affymetrix ID 203550_s_at,也可以发现类似的结果,相应的 HR 分别为 1.49(1.24,1.8)、1.49(1.21,1.83)和 1.66(1.32,2.08)。

MEM、COXPRESdb 共表达基因和 GC 的 DEGs 的相互作用最终生成了 368 个基因,KEGG 富集的通路是细胞周期通路。

总之,FAM189B 蛋白和 mRNA 的过表达可能会增加 GC 的发生率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e925/8172284/5d604dd8fc75/BMRI2021-8875971.001.jpg

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