MEOX1 Promotes Tumor Progression and Predicts Poor Prognosis in Human Non-Small-Cell Lung Cancer

Abstract

Background: MEOX1 is a homeobox transcriptional factor, and plays essential roles in regulating somite development. Our previous study indicated that MEOX1 is a critical molecular target in mesenchymal-like cancer cells in PTEN-deficient Trastuzumab resistant breast cancer. Despite the potential implication of MEOX1 for the cancer progression, no previous studies examined its level and clinical significance in lung cancer tissues. In this study, we aimed to detect the MEOX1 expression and correlate its level with clinical outcome in non-small-cell lung cancer patients (NSCLC).Methods: MEOX1 gene expression in lung cancer was examined by using the Oncomine database. MEOX1 protein levels were evaluated by IHC using the corresponding primary antibody on two different commercial lung cancer tissue arrays. siRNA knockdown was used to elucidate the function of MEOX1.Results: Analysis of the Oncomine datasets identified that an elevation of MEOX1 in gene amplification in lung cancer tissues in comparison to normal lung tissues. Immunohistochemistical analysis demonstrated that MEOX1 was localized predominantly in the nucleus, and positive rate was 67.3% (111/165) in NSCLC samples. Statistical analysis revealed high levels of MEOX1 significantly correlated with Lymph Node Metastasis and Stage. Kaplan-Meier survival analysis showed that high levels of MEOX1 were significantly associated with unfavorable survival in NSCLC patients, and MEOX1 nucleus staining had worse survival, than did patients with overall expression in lung squamous cell carcinoma patients. Multivariate Cox's regression analysis found that MEOX1 was an independent poor prognostic predictor for patients with NSCLC. Silencing of MEOX1 by specific SiRNA significantly inhibited H460 and H1299 cell proliferation and sphere formation in serum-free medium.Conclusions: Our results firstly indentified that high levels of MEOX1 especially nuclear staining was an independent prognostic factor for NSCLC, and it served a essential roles in the regulation of cell proliferation and colony formation in vitro. It may represent a potential target for the NSCLC treatment.

Stoichioproteomics reveal oxygen usage bias, key proteins and pathways in glioma

“…CCR9 associated with T lymphocyte development when bound to its specific ligand, and is highly expressed in variety of cancers [53]. MEOX1 plays key role in regulating somite development, which associated with cancer progression [54]. ADGRE5 was closely related with tumor cell adhesion, migration, angiogenesis, and apoptosis [55].…”

TIM-3 Expression Is Downregulated on Human NK Cells in Response to Cancer Targets in Synergy with Activation

“…Transcriptional data point to a nuanced role of TIM-3 in GBM. The association between high TIM-3 expression and the downregulation of genes including MEOX1, CAPN6, PRAC1 and CXCL17 in GBM suggests the role of this receptor may not be fully inhibitory, owing to the pro-tumorigenic roles that have been described for these genes [ 44 , 45 , 46 , 47 , 48 ]. TIM-3, instead, appears to be involved in a varied set of immunological responses in GBM.…”

MEOX1 is a risk factor for unfavorable prognosis in human endometrioid endometrial adenocarcinoma

“…Previous studies showed that MEOX1 may be involved in the development of some carcinoma. MEOX1 was over expressed in several cancers than normal tissues, such as prostate cancer, ovarian cancer, non-small-cell lung cancer and breast cancer [7,8,18,19]. Also, MEOX1 is related to signaling pathway.…”

“…The expression of MEOX1 was evaluated by semiquantitative method [8]. The number of positive cancer cell was scored between 0 to 3 (0, 0%; 1, ≦25%; 2, 26%-50%; 3, ≥ 50%).…”

“…MEOX1 is a cofactor of PBX1 and a pivotal target gene [6]. Besides, MEOX1 affected the progression of triple-negative breast cancer [7,8]. In addition, siRNA knockdown inhibits breast cancer cell frequency and the growth of tumor through down-regulation of MEOX1 [9].…”