Li-Ke Yu

Serum VEGF level is associated with the outcome of patients with hepatocellular carcinoma: a meta-analysis

BACKGROUND Hepatocellular carcinoma (HCC) is a highly vascular tumor that expresses vascular endothelial growth factor (VEGF). Various studies have evaluated the prognostic value of VEGF levels in HCC, but yielded conflicting results. METHODS Electronic databases updated to June 2013 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between serum VEGF level and survival of patients with HCC. Survival data were aggregated and quantitatively analyzed. RESULTS We performed a meta-analysis of 11 studies that evaluated the correlation between serum VEGF level and survival in patients with HCC. Combined hazard ratios suggested that serum VEGF level had an unfavorable impact on overall survival (OS) [hazard ratio (HR) =1.88, 95% confidence interval (CI): 1.46-2.30], and disease free survival (DFS) (HR=2.27, 95% CI: 1.55-2.98) in patients with HCC. No significant heterogeneity was observed among all studies. CONCLUSIONS Serum high VEGF level indicates a poor prognosis for patients with hepatocellular carcinoma.

Megestrol acetate in cancer patients with anorexia-cachexia syndrome: a meta-analysis

Background: Anorexia-cachexia syndrome (ACS) often occurs in patients with advanced cancer. To evaluate the effect of megestrol acetate (MA) in cancer patients with ACS, a meta-analysis of published randomized controlled trials (RCT) was performed. Methods: The databases of PubMed and Web of Science were searched from January 1966 until April 2013 and abstracts presented at American Society of Clinical Oncology conferences were searched to identify relevant clinical trials. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated. Results: Data from a total of 1,142 cancer patients with ACS in 11 RCTs were identified and included for meta-analysis. Cancer patients with ACS who received MA had increased weight gain (179 events among 534 patients treated with MA vs . 83 events among 447 control patients; RR 2.17; 95% CI: 1.59-2.97), and increased appetite improvement (174 events among 321 patients treated with MA vs . 53 events among 280 control patients; RR 4.68; 95% CI: 3.25-6.76). Conclusions: The use of MA can improve appetite and is associated with weight gain in cancer patients with ACS. Despite the fact that these patients are receiving palliative care they should be informed of the risks involved in taking MA.

Special AT-rich sequence-binding protein 1 promotes cell growth and metastasis in colorectal cancer

AIM To evaluate the expression of special AT-rich sequence-binding protein 1 (SATB1) gene in colorectal cancer and its role in colorectal cancer cell proliferation and invasion. METHODS Immunohistochemistry was used to detect the protein expression of SATB1 in 30 colorectal cancer (CRC) tissue samples and pair-matched adjacent non-tumor samples. Cell growth was investigated after enhancing expression of SATB1. Wound-healing assay and Transwell assay were used to investigate the impact of SATB1 on migratory and invasive abilities of SW480 cells in vitro. Nude mice that received subcutaneous implantation or lateral tail vein were used to study the effects of SATB1 on tumor growth or metastasis in vivo. RESULTS SATB1 was over-expressed in CRC tissues and CRC cell lines. SATB1 promotes cell proliferation and cell cycle progression in CRC SW480 cells. SATB1 overexpression could promote cell growth in vivo. In addition, SATB1 could significantly raise the ability of cell migration and invasion in vitro and promote the ability of tumor metastasis in vivo. SATB1 could up-regulate matrix metalloproteases 2, 9, cyclin D1 and vimentin, meanwhile SATB1 could down-regulate E-cadherin in CRC. CONCLUSION SATB1 acts as a potential growth and metastasis promoter in CRC. SATB1 may be useful as a therapeutic target for CRC.

Prognostic significance of vascular endothelial growth factor expression in hepatocellular carcinoma tissue: a meta-analysis

BACKGROUND Vascular endothelial growth factor (VEGF) is considered as a prime mediator of angiogenesis, and has been implicated in carcinogenesis and metastasis. Various studies examined the relationship between VEGF overexpression with the clinical outcome in patients with hepatocellular carcinoma (HCC), but yielded conflicting results. METHODS Electronic databases updated to June 2013 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between VEGF overexpression and survival of patients with HCC. Survival data were aggregated and quantitatively analyzed. RESULTS We performed a meta-analysis of 14 studies that evaluated the correlation between VEGF overexpression and survival in patients with HCC. Combined hazard ratios suggested that VEGF overexpression had an unfavorable impact on overall survival (OS) [hazard ratio (HR) =1.42, 95% confidence interval (CI): 1.42-1.7], but not disease free survival (DFS) (HR=1.13, 95% CI: 0.89-1.38) in patients with HCC. No significant heterogeneity (P=0.949) was observed among 9 studies for OS, however significant heterogeneity (P=0.008) was observed among 11 studies for DFS. CONCLUSIONS VEGF overexpression indicates a poor prognosis for patients with HCC.

Detection of EML4-ALK in Lung Adenocarcinoma Using Pleural Effusion with FISH, IHC, and RT-PCR Methods

Anaplastic lymphoma kinase (ALK) and echinoderm microtubule-associated protein-like 4 (EML4) gene rearrangements occur in approximately 5% of non-small-cell lung cancers (NSCLC), leading to the overexpression of anaplastic lymphoma kinase and predicting a response to the targeted inhibitor, crizotinib. Malignant pleural effusion occurs in most patients with advanced lung cancer, especially adenocarcinoma, and tissue samples are not always available from these patients. We attempted to clarify the feasibility of detecting the EML4-ALK fusion gene in pleural effusion cells using different methods. We obtained 66 samples of pleural effusion from NSCLC patients. The pleural effusion fluid was centrifuged, and the cellular components obtained were formalin fixed and paraffin embedded. The EML4-ALK fusion gene status was determined with fluorescent in situ hybridization (FISH), reverse transcription—polymerase chain reaction (RT-PCR), and immunohistochemistry (IHC). EML4-ALK was detected in three of 66 patient samples (4.5%) with RT-PCR. When the RT-PCR data were used as the standard, one false positive and one false negative samples were identified with IHC; and one false negative sample was identified with FISH. These results suggest that a block of pleural effusion cells can be used to detect the EML4-ALK fusion gene. IHC had good sensitivity, but low specificity. FISH had low sensitivity, but high specificity. RT-PCR is a good candidate method for detecting EML4-ALK in blocks of pleural effusion cells from lung cancer patients.

Long Noncoding RNAs Expression Patterns Associated with Chemo Response to Cisplatin Based Chemotherapy in Lung Squamous Cell Carcinoma Patients

Background There is large variability among lung squamous cell carcinoma patients in response to treatment with cisplatin based chemotherapy. LncRNA is potentially a new type of predictive marker that can identify subgroups of patients who benefit from chemotherapy and it will have great value for treatment guidance. Methods Differentially expressed lncRNAs and mRNA were identified using microarray profiling of tumors with partial response (PR) vs. with progressive disease (PD) from advanced lung squamous cell carcinoma patients treated with cisplatin based chemotherapy and validated by quantitative real-time PCR (qPCR). Furthermore, the expression of AC006050.3-003 was assessed in another 60 tumor samples. Results Compared with the PD samples, 953 lncRNAs were consistently upregulated and 749 lncRNAs were downregulated consistently among the differentially expressed lncRNAs in PR samples (Fold Change≥2.0-fold, p <0.05). Pathway analyses showed that some classical pathways, including “Nucleotide excision repair,” that participated in cisplatin chemo response were differentially expressed between PR and PD samples. Coding-non-coding gene co-expression network identified many lncRNAs, such as lncRNA AC006050.3-003, that potentially played a key role in chemo response. The expression of lncRNA AC006050.3-003 was significantly lower in PR samples compared to the PD samples in another 60 lung squamous cell carcinoma patients. Receiver operating characteristic curve analysis revealed that lncRNA AC006050.3-003 was a valuable biomarker for differentiating PR patients from PD patients with an area under the curve of 0.887 (95% confidence interval 0.779, 0.954). Conclusions LncRNAs seem to be involved in cisplatin-based chemo response and may serve as biomarkers for treatment response and candidates for therapy targets in lung squamous cell carcinoma.

Prognostic value of TTF-1 expression in patients with non-small cell lung cancer: a meta-analysis

Background: Observational studies on the prognostic role of thyroid transcription factor 1 (TTF-1) in non-small cell lung cancer (NSCLC) are controversial. Methods: To clarify the impact of TTF-1 in NSCLC survival, we performed this meta-analysis that included eligible studies. The combined hazard ratios and their corresponding 95% confidence intervals were calculated in terms of overall survival. Results: A total of 17 studies with 2,235 patients were evaluable for this meta-analysis. The studies were categorized by histology, disease stage and patient race. Our results suggested that TTF-1 overexpression had a favorable impact on survival of patients with NSCLC, the HR (95% CI) was 0.49 (0.42 to 0.55) overall, 0.46 (0.38-0.54) in Asian patients, 0.52 (0.42-0.63) in non-Asian patients, 0.45 (0.38-0.52) in adenocarcinoma, 0.63 (0.39-0.86) in stage I NSCLC, 0.43 (0.33-0.53) in stage IIIb-IV NSCLC. The data collected were not sufficient to determine the prognostic value of VEGF in patients with squamous cell lung carcinomas. But there was a high heterogeneity between the studies. Conclusions: TTF-1 overexpression indicates a favorable prognosis for patients with NSCLC, this effect appears also significant when the analysis is restricted in lung AC patients, stage I and stage IIIb-IV NSCLC.

Overexpression of HP1γ is associated with poor prognosis in non-small cell lung cancer cell through promoting cell survival

Heterochromatin protein 1γ (HP1γ), which binds to di- or trimethylated lysine 9 on histone H3 (H3K9), plays an important role in chromatin packaging and gene transcriptional regulation. Recently, HP1γ has been implicated in cancer development. However, its clinical relevance and functional role in non-small cell lung cancer (NSCLC) remain elusive. In this study, we found that HP1γ expression was elevated in NSCLC samples at the messenger RNA (mRNA) level compared to adjacent normal lung tissues. In a cohort of 108 NSCLC patients, HP1γ overexpression is significantly associated with N stage (P = 0.003), pathological tumor–node–metastasis (TNM) stage (P = 0.013), smoking status (P = 0.009), and gender (P = 0.042). Patients with a high level of HP1γ expression showed a poorer overall survival rate than those with low HP1γ expression (P = 0.017). Multivariate analysis revealed that HP1γ expression is an independent prognostic marker. We also found knockdown of HP1γ in A549 and NCI-H1975 cells induced apoptosis accompanied with suppressed cell proliferation and colony formation. Consistently, pro-apoptotic proteins, Bax and GADD45α, were upregulated in response to HP1γ depletion. Altogether, our data suggested that HP1γ plays an important role in promoting NSCLC and may represent a novel prognostic biomarker and therapeutic target for the disease.

TP53 mutation is associated with a poor outcome for patients with hepatocellular carcinoma: evidence from a meta-analysis

BACKGROUND Various studies examined the relationship between p53 mutation with the clinical outcome in patients with hepatocellular carcinoma (HCC), but yielded conflicting results. METHODS Electronic databases updated to July 2013 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between p53 mutation and survival of patients with HCC. Survival data were aggregated and quantitatively analyzed. RESULTS We performed a meta-analysis of 9 studies that evaluated the correlation between p53 mutation and survival in patients with HCC. Combined hazard ratios suggested that p53 mutation had an unfavorable impact on overall survival (OS) [hazard ratio (HR) =1.46, 95% confidence interval (CI): 1.15-1.76], and disease free survival (DFS) (HR =2.57, 95% CI: 1.46-3.68) in patients with HCC. The significant heterogeneity (P=0.035) was observed among 8 studies for OS, however no significant heterogeneity (P=0.597) was observed among 5 studies for DFS. CONCLUSIONS p53 mutation indicates a poor prognosis for patients with hepatocellular carcinoma.

VEGF is associated with the poor survival of patients with prostate cancer: a meta-analysis

Background Vascular endothelial growth factor (VEGF) is considered as a prime mediator of angiogenesis, and has been implicated in carcinogenesis and metastasis. Various studies examined the relationship between VEGF overexpression with the clinical outcome in patients with prostate cancer, but yielded conflicting results. Methods Electronic databases updated to July 2013 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between VEGF status and survival of patients with prostate cancer. Survival data were aggregated and quantitatively analyzed. Results We performed a meta-analysis of 9 studies that evaluated the correlation between VEGF overexpression and survival in patients with prostate cancer. Combined hazard ratios suggested VEGF overexpression had an unfavorable impact on overall survival (OS) [hazard ratio (HR) =1.54, 95% CI (confidence interval): 1.25-1.83], but not disease free survival (DFS) (HR=1.23, 95% CI: 0.99-1.47) in patients with prostate cancer. No significant heterogeneity was observed among all studies. Conclusions VEGF overexpression indicates a poor prognosis for patients with prostate cancer.