Dataset Information

High cripto-1 and low miR-205 expression levels as prognostic markers in early stage non-small cell lung cancer.

ABSTRACT:

Objectives

Cripto-1 (CR-1) plays a critical role in the activation of SMAD, SRC, and epithelial-to-mesenchymal transition (EMT) pathways and has been shown to be prognostic in several cancer types. In addition, we showed that CR-1 renders EGFR-mutated NSCLC cells resistant to EGFR-TKI through the activation of SRC and EMT via miR-205 downregulation. This study aimed to investigate the correlation between expression of CR-1 and miR-205 and prognosis of NSCLC patients with or without EGFR mutations.

Materials and methods

A total of 265 patients with stage I (AJCC 6th edition) radically resected NSCLC were tested for CR-1 expression and EGFR mutations by immunohistochemistry and miR-205 expression via qPCR assay.

Results

CR-1 expression was evaluated with immunohistochemistry using a tissue microarray on 265 T1-2N0 surgical NSCLC samples. Of the 265 tumors, 250 (94%) expressed various levels of CR-1. A significant inverse correlation was identified between expression of miR-205 and CR-1. NSCLC patients (T1N0, n = 106) with high CR-1 expression had worse prognosis (shorter recurrence-free survival, p = .045) than those with low CR-1 expression. A similar trend was observed in NSCLC patients with normal preoperative carcinoembryonic antigen (CEA) levels (serum CEA levels <5 ng/ml; n = 179; p = .085); however, no significant correlation was found between CR-1 expression and survival rate in the T2N0 or high CEA groups. In addition, NSCLC patients with low miR-205 expression (n = 126) had poorer prognosis in terms of recurrence than those with high miR-205 expression (n = 127; p = .001).

Conclusion

High CR-1 expression is correlated with poor prognosis in NSCLC with low tumor burden and may be used to select high-risk patients for adjuvant chemotherapy in early NSCLC. Moreover, low miR-205 expression likely related to high CR-1 expression could be a prognostic marker for patients with NSCLC.

SUBMITTER: Park KS

PROVIDER: S-EPMC8057110 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BACKGROUND:Several treatments in non-small cell lung cancer (NSCLC) are histology-dependent, and the need for histology-related markers is increasing. MicroRNAs (miRNAs) are promising molecular markers in multiple cancers and show differences in expression depending on histological subtype. The miRNA family miR-200 has been associated with the regulation of epithelial-mesenchymal (EMT)/mesenchymal-epithelial transition (MET). EMT involves profound phenotypic changes that include the loss of cell-cell adhesion, the loss of cell polarity, and the acquisition of migratory and invasive properties that facilitates metastasis. A dual role for the miR-200 family in the prognosis of several tumors has been related to tumor cell origin. However, the prognostic role and function of miR-200 family in early-stage NSCLC adenocarcinoma and squamous cell carcinoma (SCC) have not been well established. METHODS:miRNA expression was determined using TaqMan assays in 155 tumors from resected NSCLC patients. Functional studies were conducted in three NSCLC cell lines: H23, A-549 and HCC-44. RESULTS:High miR-200c expression was associated with shorter overall survival (OS) in the entire cohort (p?=?0.024). High miR-200c (p?=?0.0004) and miR-141 (p?=?0.009) expression correlated with shorter OS in adenocarcinoma - but not in SCC. In the multivariate analysis, a risk score based on miR-141 and miR-200c expression emerged as an independent prognostic factor for OS in the entire cohort (OR, 2.787; p?=?0.033) and in adenocarcinoma patients (OR, 10.649; p?=?0.002). Functional analyses showed that miR-200c, was related to mesenchymal-epithelial transition (MET) and affected cell migration and E-cadherin levels, while overexpression of miR-141 reduced KLF6 protein levels and produced an increase of secretion of VEGFA in vitro (H23, p?=?0.04; A-549, p?=?0.03; HCC-44, p?=?0.02) and was associated with higher blood microvessel density in patient tumor samples (p<0.001). CONCLUSION:High miR-141 and miR-200c expression are associated with shorter OS in NSCLC patients with adenocarcinoma through MET and angiogenesis.