RESUMO
BACKGROUND: Postoperative recurrence is a significant problem associated with a poor prognosis. However, there is currently no consensus regarding biomarkers of recurrence. MATERIALS AND METHODS: We performed a microarray expression analysis using a combination of tumor tissues (n=2) and cell lines. We prioritized and validated candidate protein expression levels in the primary tumors. RESULTS: We prioritized 18 genes found to be up-regulated by more than four-fold in both A925LPE3 cell lines compared to the A925L cell line (lung adenocarcinoma) and in the cases of recurrence versus no recurrence, in order to find genes highly causative of metastasis. Among them, we selected transmembrane protease, serine 4 (TMPRSS4) and identified positive expression of TMPRSS4 in 93 (57.8%) patients. A significant negative association was observed only between the TMPRSS4 expression level and the N status. The univariate logistic regression models indicated that TMPRSS4 expression was an independent predictor of recurrence, as was the T and N status. CONCLUSION: TMPRSS4 expression is associated with postoperative recurrence. In addition, the current survival curves demonstrated that TMPRSS4 expression is associated with statistically significant differences in survival among patients with lung adenocarcinoma. TMPRSS4 staining can be used to predict the prognosis of such patients after surgery.
Assuntos
Adenocarcinoma/enzimologia , Biomarcadores Tumorais/metabolismo , Neoplasias Pulmonares/enzimologia , Proteínas de Membrana/metabolismo , Recidiva Local de Neoplasia , Serina Endopeptidases/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma de Pulmão , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Distribuição de Qui-Quadrado , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Modelos Logísticos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Serina Endopeptidases/genética , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Regulatory T-cells (Tregs) have a pivotal role not only in abrogating autoimmune disease, but also in tumor immune escape. The purpose of the present study was to evaluate the clinical significance of the relative expression of forkhead/winged helix transcription factor (FOXP3) and micrometastasis in the regional lymph nodes (RLNs) of patients with stage I non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The RLNs in 131 patients who underwent complete surgical resection for stage I NSCLC were collected at the time of surgery. The relative expression levels of FOXP3 and cytokeratin 19 (CK19) in RLNs were determined by quantitative RT-PCR. RESULTS: The pathological stage was diagnosed as stage IA in 97 patients (74.0%) and stage IB in 34 patients (26.0%). The relative expression levels of FOXP3 and CK19 in the RLNs were 0.062±0.0083% and 0.025±0.056%, respectively. The relative expression of FOXP3 tended to increase with increasing relative expression of CK19. The five-year overall survival rate of the patients with low expression of FOXP3 was better (90.3%) than that of patients with high expression (79.3%) (p=0.0419). A multivariate analysis using the significant variables (gender, age, histology and FOXP3 expression) showed that the FOXP3 expression in RLNs was a significant independent prognostic factor. CONCLUSION: The expression of CK19 tended to be positively correlated with the expression of FOXP3. High expression of FOXP3 in RLNs was a significant unfavorable prognostic factor in patients with stage I NSCLC.
