Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People's Republic of China.
Department of Radiation Oncology, Cancer Hospital of HuanXing ChaoYang District Beijing, Beijing, People's Republic of China.
Thorac Cancer. 2022 Jun;13(12):1850-1861. doi: 10.1111/1759-7714.14471. Epub 2022 May 15.
Although it has a poor prognosis, patients with lung adenocarcinoma (LUAD) have a relatively higher 5-year survival period. Thus, it is necessary to identify effective prognostic markers to evaluate the effect of early treatment. RS1 gene encodes retinoschisin, a key protein in congenital retinoschisis, while few studies have been reported on the association between RS1 and cancer prognosis.
We performed bioinformatic analyses based on the data obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases to demonstrate the expression level of RS1 was related to the LUAD prognosis and our findings were verified in-vitro and clinical samples. Then, we explored the potential mechanism of how RS1 expression influenced the prognosis of LUAD.
Compared with normal tissues, the RS1 expression was significantly lower in tumor tissues. The Multivariate Cox regression model showed that RS1 could be used as an independent prognostic indicator. Furthermore, we found significant differences in immune cell infiltration between RS1 high and low expression groups, and the proteasome pathway was found enriched in RS1 low expression samples.
In conclusion, our study suggests that RS1 is a novel prognostic biomarker for LUAD. Differences in immune cell infiltration and signaling pathways may contribute to the poor prognosis of LUAD caused by low RS1 expression.
虽然肺腺癌(LUAD)预后较差,但患者的 5 年生存率相对较高。因此,有必要识别有效的预后标志物来评估早期治疗的效果。RS1 基因编码视网膜蛋白聚糖,是先天性视网膜劈裂症的关键蛋白,而关于 RS1 与癌症预后的关系,目前报道较少。
我们基于从癌症基因组图谱和基因表达综合数据库中获得的数据进行了生物信息学分析,以证明 RS1 的表达水平与 LUAD 的预后相关,并在体外和临床样本中验证了我们的发现。然后,我们探讨了 RS1 表达如何影响 LUAD 预后的潜在机制。
与正常组织相比,肿瘤组织中 RS1 的表达显著降低。多变量 Cox 回归模型显示,RS1 可作为独立的预后指标。此外,我们发现 RS1 高表达和低表达组之间免疫细胞浸润存在显著差异,并且在 RS1 低表达样本中发现蛋白酶体途径富集。
总之,我们的研究表明 RS1 是 LUAD 的一种新的预后生物标志物。免疫细胞浸润和信号通路的差异可能导致 RS1 低表达导致 LUAD 预后不良。