Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
Cancer Genomics Proteomics. 2020 Sep-Oct;17(5):509-516. doi: 10.21873/cgp.20207.
Despite advances in our understanding on the pathogenesis of gastric cancer (GC), patients face a poor prognosis. To improve clinical outcomes, effective approaches to diagnosis and treatment employing new diagnostic biomarkers are required to achieve early detection and predict recurrence and prognosis.
Transcriptome analysis was conducted using surgically resected gastric tissues from four patients with metastatic GC. A total of 228 pairs of primary GC tissues and corresponding normal adjacent tissues were subjected to mRNA expression analysis. To validate our findings, we accessed an integrated microarray dataset and RNA sequencing data of GC cell lines.
We identified stimulated by retinoic acid 6 (STRA6) as a differentially overexpressed gene, which encodes a transmembrane protein that mediates the cellular uptake of retinol. To investigate how STRA6 contributes to the malignant phenotype of GC cells, we mined public datasets and found the mRNA encoding retinol binding protein 1 (RBP1), which is associated with retinoid metabolism, was co-expressed with STRA6. Furthermore, STRA6 mRNA levels were significantly higher in GC tissues compared to the corresponding noncancerous adjacent tissues of 228 surgically resected gastric tissue samples. Moreover, patients with high levels of STRA6 mRNA experienced significantly shorter disease-free survival and overall survival. Multivariate analysis revealed that high levels of STRA6 served as a significant risk factor.
Patients with high levels of STRA6 mRNA experienced significantly worse clinical outcomes, indicating that STRA6 may serve as a diagnostic and prognostic biomarker of GC.
尽管我们对胃癌(GC)的发病机制有了更深入的了解,但患者的预后仍较差。为了改善临床结果,需要采用新的诊断生物标志物来实现早期检测,并预测复发和预后,从而提供有效的诊断和治疗方法。
对 4 例转移性 GC 患者手术切除的胃组织进行了转录组分析。对 228 对原发性 GC 组织和相应的正常相邻组织进行了 mRNA 表达分析。为了验证我们的发现,我们还访问了一个综合的 GC 细胞系的微阵列数据集和 RNA 测序数据。
我们确定了视黄酸受体应答基因 6(STRA6)作为一个差异过表达基因,其编码一种介导视黄醇细胞摄取的跨膜蛋白。为了研究 STRA6 如何促进 GC 细胞的恶性表型,我们挖掘了公共数据集,发现与视黄醇代谢相关的视黄醇结合蛋白 1(RBP1)的 mRNA 与 STRA6 共表达。此外,与 228 例手术切除的胃组织样本中的相应非癌性相邻组织相比,GC 组织中 STRA6 mRNA 的水平显著升高。此外,228 例手术切除的胃组织样本中,STRA6 mRNA 水平较高的患者无病生存率和总生存率明显较低。多变量分析显示,高水平的 STRA6 是一个显著的危险因素。
STRA6 mRNA 水平较高的患者临床结局明显较差,表明 STRA6 可能作为 GC 的诊断和预后生物标志物。