OAS1 在肺腺癌中的预后价值及分子机制。

Prognostic value and molecular mechanisms of OAS1 in lung adenocarcinoma.

机构信息

Oncology Department, Zibo Hospital of Integrated Traditional Chinese and Western Medicine, Zibo City, 255022, Shandong Province, China.

Oncology Department, Zibo First Hospital, Zibo City, 255022, Shandong Province, China.

出版信息

BMC Pulm Med. 2024 Sep 27;24(1):473. doi: 10.1186/s12890-024-03206-3.

DOI:10.1186/s12890-024-03206-3

PMID:39334033

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11437775/

Abstract

BACKGROUND

The expression of 2'-5'-oligoadenylate synthetase 1 (OAS1) in lung cancer has been validated in numerous studies. However, the prognostic value of OAS1 expression in lung adenocarcinoma (LUAD) still remains unclear. This study aimed to reveal the prognostic value and associated molecular mechanisms of OAS1 expression in LUAD.

METHODS

Gene expression data of LUAD were extracted from online databases. Gene and protein expression levels of OAS1 in LUAD and normal samples were revealed, followed by prognostic analysis of OAS1. Next, we conducted a thorough bioinformatics analysis to examine the enrichment of key functional and biological signaling pathways and their correlation with the abundance of immune cells. The independent prognoses, drug responses, and PPI networks associated with OAS1 were analyzed. OAS1 expression was evaluated in LUAD tissues and cell lines. OAS1 was knocked down by siRNA transfection, followed by CCK8, colony formation, and wound-healing assays.

RESULTS

Gene and protein expression levels of OAS1 in LUAD samples were significantly higher than those in normal samples (all P < 0.05). OAS1 stimulation were correlated with poor prognosis, lymph node metastasis, advanced tumor stage, immune cells, and immunomodulators. The prognostic value of OAS1 in LUAD was determined via univariate regression analysis. In total, 10 OAS1-associated genes were revealed via PPI analysis of OAS1, which were primarily enriched in functions, such as the negative regulation of viral genome replication. Transcriptional analysis revealed several OAS1-related interactions, including STAT3-miR-21-OAS1. STAT3 was overexpressed and miR-21 was expressed in LUAD cells. Upregulation of OAS1 protein was determined in LUAD tissues and cell lines. OAS1 knockdown significantly reduced proliferation and migration of LUAD cells.

CONCLUSIONS

OAS1 overexpression influenced survival and immune cell infiltration in patients with LUAD, which might be a potential prognostic gene for LUAD. Moreover, OAS1 contributed to LUAD progression by participating in STAT3-miR-21-OAS1 axis.

摘要

背景

2'-5'-寡聚腺苷酸合成酶 1（OAS1）在肺癌中的表达已在多项研究中得到验证。然而，OAS1 在肺腺癌（LUAD）中的表达的预后价值仍不清楚。本研究旨在揭示 OAS1 表达在 LUAD 中的预后价值及其相关分子机制。

方法

从在线数据库中提取 LUAD 的基因表达数据。揭示 LUAD 和正常样本中 OAS1 的基因和蛋白表达水平，然后进行 OAS1 的预后分析。接下来，我们进行了全面的生物信息学分析，以检查关键功能和生物学信号通路的富集及其与免疫细胞丰度的相关性。分析了与 OAS1 相关的独立预后、药物反应和 PPI 网络。评估了 LUAD 组织和细胞系中的 OAS1 表达。通过 siRNA 转染敲低 OAS1，然后进行 CCK8、集落形成和划痕愈合测定。

结果

LUAD 样本中的 OAS1 基因和蛋白表达水平明显高于正常样本（均 P<0.05）。OAS1 刺激与不良预后、淋巴结转移、晚期肿瘤分期、免疫细胞和免疫调节剂相关。通过单变量回归分析确定了 OAS1 在 LUAD 中的预后价值。通过 OAS1 的 PPI 分析共揭示了 10 个 OAS1 相关基因，这些基因主要富集在负调节病毒基因组复制等功能中。转录分析揭示了几个 OAS1 相关的相互作用，包括 STAT3-miR-21-OAS1。STAT3 在 LUAD 细胞中过表达，miR-21 表达。在 LUAD 组织和细胞系中检测到 OAS1 蛋白的上调。OAS1 敲低显著降低了 LUAD 细胞的增殖和迁移。