LOXL2 Expression Status Is Correlated With Molecular Characterizations of Cervical Carcinoma and Associated With Poor Cancer Survival via Epithelial-Mesenchymal Transition (EMT) Phenotype

Abstract

As molecular analyses based on high-throughput sequencing have developed, the molecular classification of cancer has facilitated clinical work. The aim of the present study was to identify a new potential therapeutic target for cervical carcinoma by molecular analyses. We firstly tested the LOXL2 expression pattern in 50 paired normal cervix and cervical carcinoma via qPCR and immunohistochemistry, and the LOXL2 expression pattern was found to be in accordance with public datasets from Gene Expression Omnibus (GEO). Then, we comprehensively rewired the 176 cervical carcinoma samples from The Cancer Genome Atlas (TCGA), subsequently clustered the samples into two groups corresponding to LOXL2 expression to determined the associations between LOXL2 expression status and molecular characterizations of cervical carcinoma. In vitro assays for further verifying the correlations in SiHa-shLOXL2 and HeLa-shLOXL2 cell lines. In this study, we found that LOXL2 highly expressed in carcinoma tissue, with 14 CpG islands of LOXL2 promoter that were significantly and negatively associated with its expression in cervical carcinoma. And there were notable correlations among LOXL2 expression status and molecular characterizations of cervical carcinoma, including diagnostic age, HPV A7 types, mRNA molecular clusters, miRNA molecular clusters, and DNA methylation molecular clusters et al. In addition, high LOXL2 expression was negatively correlated with lower tumor mutation density, especially in EP300, ERBB2, EGFR and NOTCH2, and was negatively correlated with lower expression of APOBEC3 family genes, such as APOBEC3A, APOBEC3B, APOBEC3D, and APOBEC3G. Furthermore, high LOXL2 expression was associated with poor overall (OS) and poor disease-free survival (DFS) in cervical carcinoma, and was associated with higher epithelial-mesenchymal transition (EMT) score, enrichment of extracellular matrix (ECM) signaling, the phenotype that was found to be associated with poor prognosis Cao et al. LOXL2 With EMT in Cervical Carcinoma in cervical carcinoma from TCGA. Conversely, the ability of cell proliferation and cell migration were reversed in LOXL2 knock-down cervical cell lines via regulating the genes' expression of EMT phenotype in vitro. Overall, we demonstrated the correlation between LOXL2 expression status and cancer molecular characterizations of cervical carcinoma, and identified LOXL2 may serve as a therapeutic target for such carcinoma.

Toward Regulatory Effects of Curcumin on Transforming Growth Factor-Beta Across Different Diseases: A Review

“…However, resistance of cancer cells has limited its efficacy. EMT is a potential factor in stimulation of chemoresistance via elevating proliferation and invasion of cancer cells ( Cao et al, 2020 ). The TGF-β can induce EMT and its inhibition by miR-145 suppresses malignant behavior of cancer cells ( Chen et al, 2020a ).…”

The pathological significance of LOXL2 in pre-metastatic niche formation of HCC and its related molecular mechanism

“…So far, the identi ed tumor-derived soluble factors are still very limited for triggering pre-metastatic niche formation in HCC. LOXL2 upregulation has been identi ed to promote metastasis of gastric, breast and colorectal cancer [34][35][36], and implicates in less differentiation [37] and poor prognosis [35,38], implying a positive correlation between LOXL2 level and tumor metastasis. Except that, hypoxia-associated LOXL2 and LOX also exhibit a potential induction role in the formation of pre-metastatic niche in HCC and breast cancer [39,40].…”

Comprehensive analysis on the expression levels and prognostic values of LOX family genes in kidney renal clear cell carcinoma

“…15 Cao Canhui et al found that over-expression of LOXL2 significantly predicts poor survival in cervical cancer via remolding epithelial-mesenchymal transition (EMT). 16 Before carrying out the research, we have found that some LOX family genes, such as LOX and LOXL2, were significantly correlated with poor prognosis in many types of solid tumors (eg, bladder urothelial carcinoma, lung squamous cell carcinoma, and skin cutaneous carcinoma) using the online web tool ESurv, which was a user-friendly web tool for survival analysis. 17 Here, we aimed to comprehensively explore the expression level, prognostic values, and mutation characteristics of LOX family genes in KIRC, and identify promising biomarkers that may play key roles in the occurrence and development of KIRC.…”

“…Hiroaki Kasashima et al found LOXL1, LOXL3, and LOXL4 are significantly correlated with distant metastasis in gastric cancer 15 . Cao Canhui et al found that over‐expression of LOXL2 significantly predicts poor survival in cervical cancer via remolding epithelial‐mesenchymal transition (EMT) 16 …”