PDF(Pubmed)
Abstract：
Gastric carcinoma is the fourth most prevalent cause of cancer-related deaths worldwide because of dismal prognosis and few therapeutic options. Accumulated studies have indicated that targeting lysyl oxidase (LOX) family members may serve as an anticancer strategy. Nevertheless, the specific mechanisms of LOX in stomach carcinoma are still unclear. In this study, we demonstrated that LOX is significantly different in 13 types of cancers and may act as a potential therapeutic target, especially in stomach carcinoma. Moreover, overexpression of LOX in gastric carcinoma was validated by multiple databases and contributed to the poor overall survival (OS), progression-free survival (PFS) and post-progression survival (PPS) of stomach adenocarcinoma (STAD) patients. Next, based on the ceRNA hypothesis, the HIF1A-AS2/RP11-366L20.2-miR-29c axis was characterized as the upstream regulatory mechanism of LOX gene overexpression in gastric cancer by combining correlation analysis, expression analysis, and survival analysis. Finally, we illustrated that LOX gene overexpression leads to dismal prognosis of gastric cancer, perhaps through promoting M2 macrophage polarization and tumor immune escape and enhancing drug resistance of tumor cells to chemotherapeutic drugs. Our research demonstrate that LOX may be potentially applied as a novel prognostic marker and targeting inhibition of LOX holds promise as a treatment strategy for gastric cancer.
摘要：
由于预后不佳和治疗选择很少，胃癌是全球癌症相关死亡的第四大流行原因。越来越多的研究表明，靶向赖氨酰氧化酶（LOX）家族成员可以作为一种抗癌策略。然而，LOX在胃癌中的具体机制尚不清楚。在这项研究中,我们证明了LOX在13种癌症中存在显着差异，并且可能作为潜在的治疗靶标，尤其是胃癌.此外，通过多个数据库验证了LOX在胃癌中的过度表达，并导致总体生存率（OS）较差，胃腺癌（STAD）患者的无进展生存期（PFS）和进展后生存期（PPS）。接下来,基于CERNA假设，结合相关性分析,HIF1A-AS2/RP11-366L20.2-miR-29c轴是胃癌LOX基因过表达的上游调控机制,表达分析,和生存分析。最后,我们说明LOX基因过度表达导致胃癌预后不良,可能通过促进M2巨噬细胞极化和肿瘤免疫逃逸以及增强肿瘤细胞对化疗药物的耐药性。我们的研究表明，LOX可能作为一种新的预后标志物，靶向抑制LOX有望作为胃癌的治疗策略。
