LncRNA/miR-29c-Mediated High Expression of LOX Can Influence the Immune Status and Chemosensitivity and Can Forecast the Poor Prognosis of Gastric Cancer.

Aitao Nai,Shoaib Bashir,Wei Wan,Huihui Zeng,Feng Ma,Qiong Wu,Meng Xu,Jie He,Shuwen Zeng,Zirui He

doi:10.3389/fcell.2021.760470

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.

Highlights

Gastric cancer (GC) is a malignant tumor with relatively high morbidity and is the fourth most prevalent cause of cancer-related deaths worldwide and the second most prevalent cause of cancerrelated deaths in China (Sung et al, 2021; Wu et al, 2020), which resulted in a considerable health burden
The results revealed that lysyl oxidase (LOX) mRNA expression was considerably increased in the vast majority of human cancers compared with non-cancer tissues, such as cervical squamous cell carcinoma, endocervical adenocarcinoma, cholangiocarcinoma, colon adenocarcinoma, esophageal carcinoma, glioblastoma multiforme, head and neck squamous cell carcinoma, kidney renal clear cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, prostate adenocarcinoma, rectal adenocarcinoma, and stomach adenocarcinoma, while it was markedly lower in thyroid carcinoma
These results indicate that LOX has a considerably different expression in most malignancies, and it may function as a potential oncogene, in gastric carcinoma

Summary

Introduction

Gastric cancer (GC) is a malignant tumor with relatively high morbidity and is the fourth most prevalent cause of cancer-related deaths worldwide and the second most prevalent cause of cancerrelated deaths in China (Sung et al, 2021; Wu et al, 2020), which resulted in a considerable health burden. In spite of emerging progress in medical therapy and technology, the 5-year overall survival rate of patients with GC remains not satisfactory (Zhu et al, 2020). These features, such as the lack of LOX in Prognosis of STAD early diagnostic techniques and effective treatment strategies, may account for the short survival in gastric cancer (Huang et al, 2015). Accumulated studies suggest that LOX is closely related to tumor cell proliferation, migration, invasion, and metastasis (Ye et al, 2020; Li et al, 2019) and is perhaps a potential molecular target for tumor therapy (Setargew et al, 2021). The detailed biological function of LOX in gastric cancer is still poorly understood

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