The improvement in histological diagnostic tools, including neuroendocrine markers by immunohistochemistry (IHC), has led to increased recognition of non-small cell lung cancer (NSCLC) with neuroendocrine (NE) feature. However, little is known regarding the prevalence and clinical implications of NE feature in patients with NSCLC. In this study, we performed IHC in a tissue microarray containing 451 Chinese NSCLC cases, and analyzed correlation of the expression of neuroendocrine marker with pathological and clinical features of NSCLC. The result showed that NE feature in NSCLC was detectable in almost 30% of studied patients, and tumors with NE feature were significantly correlated with pathological classification, clinical stages and cell differentiation of NSCLC. Our data also revealed that NE feature indicated worse overall survival and disease free survival. Compared with mutant p53, NE markers showed more significance as for prognostic evaluation. Multi-factor COX analysis further suggested a potential clinical impact for NE feature as an independent indicator of poor prognosis for NSCLC patients.
Background Wogonin is a plant monoflavonoid and has been reported to induce apoptosis of cancer cells and show inhibitory effect on cancer cell growth. However, the detailed and underlying molecular mechanisms are not elucidated. In this study, we investigated the molecular and biological effects of wogonin in human ovarian A2780 cancer cells. Materials and Methods We determined the effects of wogonin on the changes of cell cycling and apoptotic responses of cells. Western blot analysis was used to measure the effects of wogonin on protein expressions. Results Our results showed that treatment with wogonin inhibited the cancer cell proliferation, decreased the percentage of G0/G1 subpopulation, and reduced invasiveness of A2780 cells. Exposure to wogonin also resulted in downregulated protein levels of estrogen receptor alpha (ER-α), VEGF, Bcl-2, and Akt and increased expressions of Bax and p53. In addition, exposure to wogonin increased caspase-3 cleavage and induced apoptosis in A2780 cells. Our study further showed that MPP, a specific ER-α inhibitor, significantly enhanced antitumor effects of wogonin in A2780 cells. Conclusion Our results suggest a potential clinical impact of wogonin on management of ovarian cancer.
Because NSCLC has poor overall prognosis and is frequently diagnosed at later stage, we aimed to seek novel diagnosis biomarkers or therapy target of the disease in this study. Fructose-1,6-bisphosphatase 1 (FBP1) is a rate-limiting enzyme in gluconeogenesis, which was usually lost in NSCLC due to abnormal methylation in promoter DNA sequence. The clinical data indicated that the methylation rate in FBP1 gene promoter was negatively related to the overall survival of the NSCLC patients. DNA methylation transferase inhibitor 5-aza treatment could significantly increase both expression levels of mRNA and protein in A549 cell line. On the other hand, silence of FBP1 in H460 cell line by using specific siRNA against FBP1 dramatically improved the cell proliferation and cell migration according to the date of FACS and transwell assays. All these findings implied the important roles of FBP1 expression in lung cancer development and progression and the potential use of the methylation status detected in FBP1 promoter region as a novel predictor for prognosis and therapeutic target for NSCLC patients.
Transglutaminase 2 (TG2) plays important roles in cell survival and cancer progression. In this study, we examined TG2 expression in specimen of 194 patients diagnosed with non-small cell lung cancer (NSCLC), and found that the TG2 gene expression was significantly higher in lung cancer tissues as compared to paired incisal marginal tissues or normal tissues. Our data revealed that patients with lower level of TG2 expression detected in cancer tissues had longer disease free survival and overall survival as compared to the patients with higher TG2 expression. We also found that TG2 expression level correlated to NSCLC recurrence. These results suggest a potential prognosis impact of TG2 for NSCLC patients.
The overall survival rate of patients with non-small cell lung cancer (NSCLC) following resection remains poor due to the high rates of recurrence and metastasis. The investigation of novel biomarkers is clinically necessary to improve treatment strategies. Multidrug resistance-associated protein 1 (MRP1) and platelet count are linked to a poor prognosis in various types of cancer. However, it is unknown whether MRP1 or platelet count is a suitable prognostic indicator of NSCLC. In the present study, 427 patients with operable NSCLC were enlisted. The association of MRP1 expression and platelet count with clinical pathological factors and patient outcome was evaluated. MRP1 expression was found to be significantly associated with sex, histological type and tumor differentiation, while platelet count was significantly associated with smoking behavior, histological type and clinical stage. Platelet count was significantly higher in patients with negative MRP1 expression than in those with positive MRP1 expression. Survival analysis indicated that there was no association between MRP1 expression and disease-free survival (DFS) or overall survival (OS) time. In the patients with no lymph node metastasis, the OS time was significantly longer in patients with positive MRP1 expression than in those with negative expression. However, in the patients with lymph node metastasis, the DFS time was significantly shorter in patients with positive MRP1 expression than in those with negative expression. There was an association between the platelet count and DFS and OS times, which were significantly longer in patients with a normal platelet count than in those with thrombocytosis. In conclusion, MRP1 expression and platelet count are valuable independent prognostic biomarkers for survival in operable NSCLC.
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