Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, No. 154 Anshan Road, Tianjin, 300052, China.
Int J Med Sci. 2023 Sep 4;20(11):1399-1416. doi: 10.7150/ijms.85253. eCollection 2023.
The prognosis for gastric cancer (GC), a prevalent tumor of the digestive system, is unfavorable. The involvement of glutathione peroxidase 3 (GPX3) in tumorigenesis is significant, yet its specific role in GC remains insufficiently investigated. Thus, the aim of this study was to determine the potential impact of GPX3 on GC and elucidate the underlying mechanism. The expression and survival of GPX3 in GC were analyzed using TCGA data. Additionally, the GPX3 mRNA and protein levels in GC were also assessed using datasets from GTEx, GEPIA, and HPA. A total of 38 pairs of GC tissues, along with their adjacent normal tissues, were collected from the Tianjin Medical University General Hospital, accompanied by detailed clinical information. The expression levels of GPX3 were subsequently determined for the purpose of validation. Following expression, correlation, and survival analyses, we proceeded to investigate the upstream non-coding RNA (ncRNA) of GPX3 using starBase and miRNet. Additionally, the co-expression networks of GPX3 were examined based on LinkedOmics. Lastly, we explored the correlation between GPX3 and immune cell infiltration, as well as the biomarkers of immune cells and immune checkpoints in GC. Furthermore, the GDSC database offered valuable drug sensitivity information. A lower expression of GPX3 was observed in individuals with GC, while a higher expression of GPX3 was associated with a poorer prognosis. The DUBR/hsa-miR-502-3p/GPX3 pathway was identified as the most promising upstream ncRNA pathway related to GPX3 in GC. GO and KEGG enrichment analysis revealed that GPX3 expression was linked to coagulation cascades and cell locomotion. Furthermore, GPX3 levels in GC were positively correlated with immune cell infiltration, immune cell biomarkers, and immune checkpoint expression. The group with low GPX3 expression also exhibited increased sensitivity to 5-fluorouracil, doxorubicin, and other drugs. Collectively, we hypothesized that the potential involvement of non-coding RNAs in the downregulation of GPX3 could contribute to the inhibition of tumor formation during the malignant transition from gastritis to GC. Nevertheless, it was plausible that GPX3 may also facilitate tumor progression to advanced stages by promoting immune cell infiltration and activating immune checkpoints.
胃癌（GC）是一种常见的消化系统肿瘤，预后不佳。谷胱甘肽过氧化物酶 3（GPX3）在肿瘤发生中的作用非常重要，但它在 GC 中的具体作用仍研究不足。因此，本研究旨在确定 GPX3 对 GC 的潜在影响，并阐明其潜在机制。我们使用 TCGA 数据分析了 GC 中 GPX3 的表达和生存情况。此外，我们还使用 GTEx、GEPIA 和 HPA 中的数据集评估了 GC 中 GPX3 的 mRNA 和蛋白水平。从天津医科大学总医院收集了 38 对 GC 组织及其相邻正常组织，并附有详细的临床信息。随后，我们为验证目的测定了 GPX3 的表达水平。在进行表达、相关性和生存分析后，我们使用 starBase 和 miRNet 研究了 GPX3 的上游非编码 RNA（ncRNA）。此外，我们还根据 LinkedOmics 检查了 GPX3 的共表达网络。最后，我们探讨了 GPX3 与免疫细胞浸润的相关性，以及 GC 中免疫细胞和免疫检查点的生物标志物。此外，GDSC 数据库提供了有价值的药物敏感性信息。我们观察到 GC 患者的 GPX3 表达水平较低，而 GPX3 表达水平较高与预后较差相关。DUBR/hsa-miR-502-3p/GPX3 通路被确定为 GC 中与 GPX3 最相关的上游 ncRNA 通路。GO 和 KEGG 富集分析表明，GPX3 表达与凝血级联和细胞运动有关。此外，GC 中的 GPX3 水平与免疫细胞浸润、免疫细胞生物标志物和免疫检查点表达呈正相关。GPX3 表达水平较低的组对 5-氟尿嘧啶、阿霉素等药物的敏感性也增加。总的来说，我们假设非编码 RNA 可能参与了 GPX3 的下调，从而有助于抑制从胃炎到 GC 的恶性转化过程中的肿瘤形成。然而，GPX3 也可能通过促进免疫细胞浸润和激活免疫检查点来促进肿瘤进展到晚期阶段。
