RESUMO
BACKGROUND: Pre-resection pleural lavage cytology is useful to predict tumor recurrence and the prognosis of lung cancer patients. Recently, extracellular vesicles (EVs) isolated from effusion specimens have come under the spotlight, and several studies showed that microRNA in EVs is associated with prognosis. MicroRNA-21 (miR-21) is a representative onco-microRNA, and miR-21 in EVs (EV-miR-21) promotes cancer dissemination by inducing mesothelial to mesenchymal transition (MMT) in the peritoneal cavity. In this study, we isolated EVs from pleural lavage fluid and focused on EV-miR-21 as a diagnostic factor with a relationship to pleural dissemination. METHODS: The Cancer Genome Atlas dataset comprising of 448 cases of lung adenocarcinoma, tissue microarray of 144 cases of lung adenocarcinoma, and pleural lavage fluid of 41 cases was used to examine miR-21 expression levels. The function of EV-miR-21 was investigated in vitro. RESULTS: The miR-21 expression level in primary sites was associated with a poor prognosis and correlated with pleural invasion of adenocarcinoma. EV-miR-21 levels in pleural lavage fluid were associated with positive cytology and pleural invasion in the primary sites, even in cytology-negative cases. In vitro studies demonstrated that EV-miR-21 induces the MMT. Mesothelial cells in the MMT showed functions similar to cancer-associated fibroblasts, which are an important stromal component in primary sites and disseminated pleural lesions. CONCLUSIONS: EV-miR-21 in pleural lavage fluid is important as a diagnostic and prognostic factor. Moreover, EV-miR-21 induces the MMT, which can form premetastatic niches of dissemination in the pleural cavity.
Assuntos
Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/metabolismo , Vesículas Extracelulares/patologia , Regulação Neoplásica da Expressão Gênica , Mesoderma/patologia , MicroRNAs/genética , Derrame Pleural Maligno/patologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células , Transição Epitelial-Mesenquimal , Vesículas Extracelulares/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Mesoderma/metabolismo , Pessoa de Meia-Idade , Derrame Pleural Maligno/metabolismo , Prognóstico , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
BACKGROUND/AIM: CD10 function in urothelial carcinoma (UC) remains controversial. We previously reported that miR-21 in UC may be a prognostic marker for cancer progression. The aim of this study was to examine the clinicopathological significance of CD10 expression in UC and its relationship with miR-21 expression. MATERIALS AND METHODS: Immunohistochemistry for CD10 was performed on 232 UCs. CD10 expression in TCs and stroma was evaluated respectively, and its association with carcinogenesis and survival was analyzed. RESULTS: High tumorous CD10 was significantly associated with higher tumor stage, histological grade and vessel infiltration, and poorer prognosis, whereas stromal CD10 was significantly associated with younger age, higher tumor stage, and vessel infiltration. On multivariable analysis, CD10 expression in TCs, miR-21 expression in TCs and TS, and tumor stage were independent prognostic factors. CONCLUSION: Tumorous CD10 is more strongly related to progression of UC than stromal CD10 and is an independent factor for UC prognosis.
