Human Cripto-1 (CR-1) plays an important oncogenic role during tumorigenesis and is overexpressed in a wide range of carcinomas, yet little is known about CR-1 in non-small cell lung cancer (NSCLC). The aims of this study were to detect CR-1 expression in NSCLC and to analyze its association with prognosis of NSCLC patients. The expression of CR-1 messenger RNA (mRNA) and protein in 35 cases of NSCLC and corresponding noncancerous tissue samples was examined by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. Immunohistochemistry was performed to detect the expression of CR-1 in 128 NSCLC tissues. The expression levels of CR-1 mRNA and protein in NSCLC tissues were significantly higher than those in corresponding noncancerous tissues (P < 0.001). A high level of CR-1 expression was correlated with poor tumor differentiation (P = 0.002), tumor-node-metastasis (TNM) stage (P = 0.004), and lymph node metastasis (P = 0.001). The results of the Kaplan-Meier analysis indicated that a high expression level of CR-1 resulted in a significantly poor prognosis of NSCLC patients. Multivariate Cox regression analysis revealed that CR-1 expression level was an independent prognostic parameter for the overall survival rate of NSCLC patients. Our data suggest that the high expression of CR-1 may play an important role in the progression of NSCLC, and CR-1 expression may offer a valuable marker for predicting the outcome of patients with NSCLC.

Histone methylations play important roles in human cancer metastasis. Enhancer of zeste homolog 2 (EZH2) is a key component of the polycomb repressor complex 2, which is responsible for histone H3K27 methylation. EZH2 is overexpressed in lung cancer and epigenetically silences tumor suppressor genes. Here, we showed that EZH2 was up-regulated in lung cancer and had a positive correlation with pathologic stage, nodal involvement in lung cancer patients. Moreover, overexpression of EZH2 was correlated with reduced tissue inhibitor of metalloproteinase-3 (TIMP-3) expression, which was shown to be negatively associated with tumor metastasis. Of note, overall survival time of patients with high EZH2/low TIMP-3 expression was significantly shorter than that of patients with low EZH2/high TIMP-3 (P = 0.031). RNA interfering and pharmacologic inhibition of EZH2 reduced histone H3 lysine 27 tri-methylation level and increased TIMP-3 expression level. Knockdown of EZH2 by siRNA significantly reduced A549 cancer cell migration. In contrast, reduction of TIMP-3 in A549 cells partially rescued EZH2 deficiency-induced loss of cell migration capacity. Taken together, our findings indicate that EZH2 accelerates cancer cell migration, in part, via the repression of TIMP-3 expression, suggesting a potential mechanism by which EZH2 promotes lung cancer progression and metastasis.

Abstrac Background Rapid on‐site evaluation (ROSE) has the potential to increase endobronchial ultrasound (EBUS) guide transbronchial lung biopsy (TBLB) accuracy in the diagnosis of peripheral pulmonary lesions (PPLs). However, studies have reported controversial results. The aim of the study was to evaluate the diagnostic value of EBUS‐TBLB combination with ROSE in PPLs. Methods A total of 152 patients with PPLs underwent EBUS were enrolled and completed this study. Patients were divided into EBUS combined with ROSE group (EBUS+ROSE group) and EBUS group (EBUS group). The diagnostic yield, operation time, and complications were compared between the two groups. Results The diagnostic yield in EBUS+ROSE group was 85.9%, the operation time was (24.6 ± 6.8) min, the diagnostic yield in EBUS group was 70.3%, and the operative time was (32.4 ± 8.7) min, there were significant differences in diagnostic yield (χ2 = 5.456, P = .016) and operation time (t = 3.167, P = .001) between the two groups. No severe procedure related complications were observed, such as, pneumothorax and hemorrhage. Conclusions ROSE can improve the diagnostic yield and shorten the operation time. EBUS combined with ROSE is an effective diagnostic method for PPLs.

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Cripto‐1 (CR‐1) is related to the biological behaviour and prognosis of carcinomas. The purpose of this study was to investigate the significance of CR‐1 expression in surgically resected stage I non‐small cell lung cancer (NSCLC). One hundred and forty‐eight patients with completely resected stage I NSCLC and available clinical follow‐up data were assessed. The protein expression of CR‐1 in the tumours was detected by immunohistochemistry. CR‐1 was highly expressed in 64 of 148 tumours. Among patients with high CR‐1 expression, progression‐free survival and overall survival rate were significantly lower than those of patients with low CR‐1 levels (P = .013 and P = .019, respectively). The incidence of distant metastasis in patients with high CR‐1 expression was significantly higher than that of in patients with low CR‐1 expression (57.13% vs 21.43%, P = .001). The results of the multivariate analysis confirmed that a high CR‐1 was a significant factor for poor prognosis. In conclusion, CR‐1 could be a useful prognostic factor in patients with stage I NSCLC, likely as an indicator of the metastatic propensity of the tumour.