High cripto-1 and low miR-205 expression levels as prognostic markers in early stage non-small cell lung cancer
| Autor: | Giuseppe Giaccone, Kang-Seo Park, Mark Raffeld, Yong Wha Moon, Dae Ho Lee, Yisong Wang |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Male Cancer Research Lung Neoplasms Cripto GPI-Linked Proteins Disease-Free Survival Article 03 medical and health sciences 0302 clinical medicine Carcinoembryonic antigen Downregulation and upregulation Carcinoma Non-Small-Cell Lung Biomarkers Tumor Medicine Humans Stage (cooking) Lung cancer Aged Neoplasm Staging Tissue microarray biology business.industry Cancer Middle Aged medicine.disease Prognosis Immunohistochemistry respiratory tract diseases Neoplasm Proteins ErbB Receptors MicroRNAs 030104 developmental biology Oncology Tissue Array Analysis 030220 oncology & carcinogenesis Mutation Cancer research biology.protein Intercellular Signaling Peptides and Proteins Female business |
| Zdroj: | Lung Cancer |
| ISSN: | 1872-8332 |
| Popis: | 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 < 5ng/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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect