Yafang Liu

The growth arrest-specific transcript 5 (GAS5): a pivotal tumor suppressor long noncoding RNA in human cancers

Long noncoding RNAs (lncRNAs), which refer to a group of RNAs with length more than 200 nucleotides and limited protein-coding potential, play a widespread role in regulating biological processes, such as cell differentiation, proliferation, apoptosis, and migration. LncRNAs are dysregulated in multiple cancers, playing an either oncogenic or tumor-suppressive role. LncRNA GAS5 is a recently identified tumor suppressor involved in several cancers, like breast cancer, prostate cancer, lung cancer, and colorectal cancer. The low-expression pattern confers tumor cells elevated capacity of proliferation and predicts poorer prognosis. Existing studies mirror that lncRNA GAS5 promises to be a novel diagnostic biomarker, therapy target, as well as prognostic biomarker. In this review, we will summarize the current knowledge about this vital lncRNA, from its discovery, characteristics, and biological function to molecular mechanism in various neoplasms.

Long intergenic noncoding RNA 00673 promotes non-small-cell lung cancer metastasis by binding with EZH2 and causing epigenetic silencing of HOXA5

Metastasis of cancer cells is a key impediment to favorable outcomes of cancer treatment. Functional roles of long noncoding RNAs in several biological processes, including metastasis, have recently been discovered. In our previous work, we reported a positive correlation of increased expression of linc00673 in NSCLC tissues with tumor size, lymph node metastasis, TNM stage, and increased proliferation of NSCLC cells, both, in vitro and in vivo. In this study, we demonstrate that ectopic expression of linc00673 promotes migration and invasion of NSCLC cells. Furthermore, our results indicate that linc00673 could silence HOXA5 expression by recruiting epigenetic repressor, EZH2, at its promoter regions. HOXA5 was identified as a tumor suppressor gene, which inhibited NSCLC cell metastasis by regulating cytoskeletal remodeling. To summarize, we for the first time identified the role of lin00673 in promoting invasion and migration of NSCLC cells. Insights from this study may help to identify novel therapeutic targets for NSCLC.

Prognostic value of the expression of estrogen receptor β in patients with non-small cell lung cancer: a meta-analysis

BACKGROUND Lung cancer remains the leading cause of cancer-related deaths in men and the second leading cause in women worldwide. It is becoming increasingly clear that estrogen and estrogen receptors are involved in the pathogenesis and development of lung cancer. However, observational studies on the prognostic role of estrogen receptor β (ERβ) in non-small cell lung cancer (NSCLC) are controversial. METHODS To clarify the impact of ERβ in NSCLC survival, we performed this meta-analysis that included eligible studies. The combined hazard ratios (HR) and their corresponding 95% confidence intervals (CIs) were calculated in terms of overall survival. RESULTS A total of eleven studies with 3,300 patients were evaluable for this meta-analysis. Our results suggested that ERβ overexpression had no relationship on survival of patients with NSCLC, the HR (95% CI) was 1.000 (0.954-1.047) overall. Moreover, there was no heterogeneity between the studies. CONCLUSIONS ERβ overexpression indicates no relationship of prognosis for patients with NSCLC.

Prognostic value of circulating endothelial cells in non-small cell lung cancer patients: a systematic review and meta-analysis

BACKGROUND Circulating endothelial cells (CECs) have been indicated as a potential biomarker of vascular damage in a variety of cancers. Several studies have revealed CECs may reflect the extent of tumor angiogenesis; however, the role of CECs in the prognosis of non-small cell lung cancer (NSCLC) is undetermined to date. A meta-analysis has been prepared to determine whether the base level of CECs and the changes of CECs after therapy (∆CECs: post-therapeutic value minus the pre- therapeutic value) could be considered as a prognostic tool for patients with NSCLC. METHODS Systematic reviews of studies published before April 30 2015 were conducted on the association between the levels of CECs or ∆CECs and the prognosis of NSCLC in several data bases. Hazard ratios (HRs) and the 95% confidence intervals (CIs) were used to collate the data. Similarly, heterogeneity and publication bias were also evaluated. RESULTS A total of nine studies, containing eight prospective studies and one retrospective study, involving 515 patients was identified. Patients with higher level of CECs counts at baseline were associated with longer progression-free survival (PFS) (HR 0.71, 95% CI: 0.529-0.891). ∆CECs could also be considered a prognostic indicator in NSCLC patients (HR 0.575, 95% CI: 0.401-0.75). The former and the later are without a significant heterogeneity in the data (I(2)=21.2% and 0.0%, P=0.274 and 0.870, respectively). However, there was no correlation between the base level of CECs and the overall survival (OS) (HR 0.914, 95% CI: 0.560-1.267, I(2)=43.6%, P=0.150). CONCLUSIONS Higher levels of CECs counts at baseline and the ensuing decrease after therapy demonstrated a positive correlation with longer PFS in NSCLC patients. But this phenomenon has not been found in OS. From a certain perspective, CECs counts and ∆CECs could be potential prognostic indicators for NSCLC patients.

The imaging of small pulmonary nodules

Lung cancer is the leading cause of cancer death worldwide. The major goal in lung cancer research is the improvement of long-term survival. Pulmonary nodules have high clinical importance, they may not only prove to be an early manifestation of lung cancer, but decide to choose the right therapy. This review will introduce the development and current situation of several imaging examination methods: computed tomography (CT), positron emission tomography/computed tomography (PET/CT), endobronchial ultrasound (EBUS).

Protein regulator of cytokinesis-1 expression: prognostic value in lung squamous cell carcinoma patients

BACKGROUND Protein regulator of cytokinesis-1 (PRC1) has been shown to participate in the completion of cytokinesis, and it is dysregulated in cancer processes. However, its relevance in lung squamous cell carcinoma (SCC) remained largely unknown. We aimed to study the expression pattern of PRC1 and assess its clinical significance in lung SCC. METHODS PRC1 protein expression in human lung SCC and adjacent normal lung tissues was detected by immunohistochemistry. PRC1 expression was assessed in association with clinicopathological features and clinical outcomes of lung SCC patients. RESULTS In lung SCC tissues, PRC1 protein expression was significantly higher than those in paired normal lung tissues. The lung SCC patients with PRC1 overexpression had an advanced pathological stage (TNM stage), positive lymph node metastasis, and a shorter overall survival (OS) time more frequently than patients with low PRC1 expression. Additional, PRC1 expression was also shown to be poor as a prognostic factor for OS in patients with lung SCC. CONCLUSIONS Our study indicated that aberrant expression of PRC1 may point to biochemical recurrence in lung SCC. This highlights its potential as a valuable prognostic marker for lung SCC.

Overexpression of geranylgeranyl diphosphate synthase contributes to tumour metastasis and correlates with poor prognosis of lung adenocarcinoma

This study aimed to evaluate the biological role of geranylgeranyl diphosphate synthase (GGPPS) in the progression of lung adenocarcinoma. GGPPS expression was detected in lung adenocarcinoma tissues by qRT‐PCR, tissue microarray (TMA) and western blotting. The relationships between GGPPS expression and the clinicopathological characteristics and prognosis of lung adenocarcinoma patients were assessed. GGPPS was down‐regulated in SPCA‐1, PC9 and A549 cells using siRNA and up‐regulated in A549 cells using an adenoviral vector. The biological roles of GGPPS in cell proliferation, apoptosis, migration and invasion were determined by MTT and colony formation assays, flow cytometry, and transwell and wound‐healing assays, respectively. In addition, the regulatory roles of GGPPS on the expression of several epithelial‐mesenchymal transition (EMT) markers were determined. Furthermore, the Rac1/Cdc42 prenylation was detected after knockdown of GGPPS in SPCA‐1 and PC9 cells. GGPPS expression was significantly increased in lung adenocarcinoma tissues compared to that in adjacent normal tissues. Overexpression of GGPPS was correlated with large tumours, high TNM stage, lymph node metastasis and poor prognosis in patients. Knockdown of GGPPS inhibited the migration and invasion of lung adenocarcinoma cells, but did not affect cell proliferation and apoptosis. Meanwhile, GGPPS inhibition significantly increased the expression of E‐cadherin and reduced the expression of N‐cadherin and vimentin in lung adenocarcinoma cells. In addition, the Rac1/Cdc42 geranylgeranylation was reduced by GGPPS knockdown. Overexpression of GGPPS correlates with poor prognosis of lung adenocarcinoma and contributes to metastasis through regulating EMT.

Chloroquine inhibits tumor growth and angiogenesis in malignant pleural effusion

Malignant pleural effusion (MPE) is associated with a poor prognosis in lung cancer. Currently, no effective cure exists for MPE. Chloroquine (CQ) has been demonstrated to induce vascular normalization and inhibit tumor growth. The aim of this study was to assess whether CQ affects MPE. The xenografts mice were divided into normal saline (NS), CQ, or bevacizumab (BE) group. Tumor growth and microvascular density (MVD) were monitored. We explored the effect of CQ on the proliferation, survival, and proangiogenic signaling of tumor cells in vitro. We further evaluated the effects of CQ on the viability, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). A chicken chorioallantoic membrane (CAM) model was used to elucidate the effects of CQ on angiogenesis. Finally, an MPE mouse model were treated by CQ, BE, or NS. The volume of pleural effusion, tumor foci, and MVD was evaluated. CQ therapy group exhibited decreased tumor volume, tumor weight, and MVD in the mouse xenografts. CQ inhibited the proliferation of the tumor cells. However, the expression of vascular endothelial growth factor was not affected. Additionally, CQ inhibited the proliferation, migration, and tube formation of HUVECs and also restrained angiogenesis in the CAM. Western blot showed that CQ might suppress angiogenesis by downregulating p-Akt, Jagged1, and Ang2 in HUVECs. In MPE mice, the volume of the pleural effusion, the number of pleural tumor foci, and the MVD were significantly reduced in the CQ group. Our work demonstrated that CQ played the role of an efficient treatment for MPE.

Is it feasible to detect epidermal growth factor receptor mutations in circulating tumor cells in nonsmall cell lung cancer?: A meta-analysis.

Background:The value of circulating tumor cells (CTCs) in detecting epidermal growth factor receptor (EGFR) mutations in patients with nonsmall cell lung cancer (NSCLC) is controversial. We performed a meta-analysis to investigate the diagnostic significance of CTCs with tumor tissues as the standard control. Methods:A systematic literature search, including papers published until November 26, 2015, was performed using PubMed, Medline, Embase, Web of Science, and the China National Knowledge Infrastructure, and the references of retrieved articles were screened. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated according to the data selection from the included studies. The evaluation indexes of the diagnostic performance were the summary receiver operating characteristic curve (SROC) and area under the SROC (AUSROC). Results:Eight eligible articles with a total of 170 participants were identified in our meta-analysis. The pooled sensitivity and specificity were 0.91 [95% CI: 0.55–0.99] and 0.99 [95% CI: 0.59–1.00]. The positive likelihood ratio and negative likelihood ratio were 68 [95% CI: 1.4–3364] and 0.09 [95% CI: 0.01–0.64], respectively. The DOR was 788 [95% CI: 9–71884]. The high diagnostic performance of CTCs in detecting EGFR mutations was indicated by the AUSROC of 0.99 [95% CI: 0.98–1.00]. Conclusions:CTCs are a feasible and highly specific biomarker for detecting the EGFR mutation status in NSCLC patients.