Liu J, Zeng M L, Shi P C, Cao Y P, Zhang J L, Xie Y P
Clin Lab. 2020 Jul 1;66(7). doi: 10.7754/Clin.Lab.2019.191015.
SCARA5 has been demonstrated to be a tumor suppressor gene, with its expression downregulated in many cancer types. However, only few studies have investigated its role in colorectal cancer (CRC). The current study evaluated SCARA5 expression levels in CRC and its potential value as a diagnostic biomarker for CRC.
Data were downloaded from the TCGA, GEO, and Oncomine databases to evaluate SCARA5 mRNA expression levels in CRC. The prognosis value of SCARA5 was assessed using the online tool Cutoff Finder via the Kaplan-Meier plotter (n = 484). Immunohistochemistry was performed to analyze and compare the SCARA5 protein expression levels in CRC and normal tissues from 67 CRC clinical specimens. Relevant CRC CNV data were downloaded from TCGA and cBioPortal for Cancer Genomics databases to assess the associated genetic alterations. GSEA was used to explore the underlying molecular mechanisms of SCARA5. The correlation between SCARA5 mRNA levels and cell cycle-associated genes was explored using GEPIA database.
SCARA5 mRNA levels were found to be downregulated in CRC tissues compared with normal tissues. Survival analysis showed that low SCARA5 expression was associated with poor prognosis. These results were validated in clinical specimens, wherein the SCARA5 protein levels were significantly downregulated in CRC tissues compared with paracarcinoma tissues. Deep deletion was the most common genetic alteration and was consistent with the downregulated SCARA5 expression in CRC tissues. GSEA indicated that the gene sets of CELL CYCLE, G2M CHECKPOINT, and E2F TARGETS were negatively related to SCARA5 mRNA expression. GEPIA indicated that the mRNA expression of some cell cycle-associated genes was negatively correlated with that of SCARA5 in CRC.
Thus, SCARA5 may act as a human cancer suppressor gene in CRC, and its expression level may be a reliable adjuvant parameter to diagnose CRC and predict tumor metastasis and prognosis.
SCARA5已被证明是一种肿瘤抑制基因，其表达在多种癌症类型中下调。然而，仅有少数研究调查了其在结直肠癌（CRC）中的作用。本研究评估了SCARA5在CRC中的表达水平及其作为CRC诊断生物标志物的潜在价值。
从TCGA、GEO和Oncomine数据库下载数据，以评估SCARA5 mRNA在CRC中的表达水平。通过Kaplan-Meier绘图仪（n = 484）使用在线工具Cutoff Finder评估SCARA5的预后价值。进行免疫组织化学分析并比较67例CRC临床标本中CRC组织和正常组织中SCARA5蛋白的表达水平。从TCGA和癌症基因组学数据库cBioPortal下载相关的CRC CNV数据，以评估相关的基因改变。使用GSEA探索SCARA5的潜在分子机制。使用GEPIA数据库探索SCARA5 mRNA水平与细胞周期相关基因之间的相关性。
发现CRC组织中SCARA5 mRNA水平与正常组织相比下调。生存分析表明，SCARA5低表达与预后不良相关。这些结果在临床标本中得到验证，其中CRC组织中SCARA5蛋白水平与癌旁组织相比明显下调。深度缺失是最常见的基因改变，与CRC组织中SCARA5表达下调一致。GSEA表明，细胞周期、G2M检查点和E2F靶点的基因集与SCARA5 mRNA表达呈负相关。GEPIA表明，CRC中一些细胞周期相关基因的mRNA表达与SCARA5呈负相关。
因此，SCARA5可能作为CRC中的一种人类癌症抑制基因，其表达水平可能是诊断CRC以及预测肿瘤转移和预后的可靠辅助参数。
