Ruting Xie

High expression of miR-105-1 positively correlates with clinical prognosis of hepatocellular carcinoma by targeting oncogene NCOA1

Increasing evidence supports that microRNA (miRNA) plays a significant functional role in cancer progression by directly regulating respective targets. In this study, the expression levels of miR-105-1 and its target gene were analyzed using genes microarray and hierarchical clustering analysis followed by validation with quantitative RT-PCR in hepatocellular carcinoma (HCC) and normal liver tissues. We examined the expression of nuclear receptor coactivator 1 (NCOA1), the potential target gene of miR-105-1, following the transfection of miR-105-1 mimics or inhibitors. Our results showed that miR-105-1 was downregulated in HCC tissues when compared with normal liver tissues and patients with lower miR-105-1 expression had shorter overall survival (OS) and progression free survival (PFS). Moreover, NCOA1 was confirmed to be a direct target of miR-105-1. Furthermore, concomitant high expression of NCOA1 and low expression of miR-105-1 correlated with a shorter median OS and PFS in HCC patients. In conclusion, our results provide the first evidence that NCOA1 is a direct target of miR-105-1 suggesting that NCOA1 and miR-105-1 may have potential prognostic value and may be useful as tumor biomarkers for the diagnosis of HCC patients.

Association of microRNA-33a Molecular Signature with Non-Small Cell Lung Cancer Diagnosis and Prognosis after Chemotherapy

Objective This study aims to explore the expression pattern and prognostic significance of miR-33a in non-small cell lung cancer (NSCLC) treated with adjuvant chemotherapy. Methods MiR-33aexpression in NSCLC was analyzed in silico using the GEO database and was subsequently confirmed by quantitative RT-PCR in 147 NSCLC biopsies. Among these, 32 of these biopsies were paired with adjacent non-neoplastic tissues. The survival analysis of NSCLC by Kaplan-Meier estimates was stratified based on miR-33a expression. In addition, multivariate survival analysis in corresponding groups of NSCLC patients was conducted by Cox proportional hazards regression model. Results The in silico analysis of miR-33a expression in NSCLC resulted to its down-regulation in different tumor types. The expression level of miR-33a was lower in each grade of NSCLC tumor biopsies than in normal lung tissues. Univariate and multivariate survival analysis further established that low miR-33a expression was an important risk factor for overall survival and disease free survival in NSCLC patients. Conclusion Our study implied that miR-33a expression levels may have an essential role in NSCLC progression, and could act as a specific and sensitive biomarker for NSCLC patients who have undergone adjuvant chemotherapy.

Up-regulated microRNA-299 corrected with poor prognosis of glioblastoma multiforme patients by targeting ELL2

Background An increasing understanding of the genes and molecular pathways of glioblastoma multiforme (GBM) can provide us a useful insight for the development of more effective targeted therapeutic. Methods To investigate the expression and clinical significance of miR-299 and its target genes in GBM, the expression levels of miR-299 and its target gene in human normal brain tissues and GBM were analyzed in silico using genes microarray and hierarchical clustering analysis followed by validation with quantitative RT-PCR. Results Our results show that miR-299 is up-regulated in GBM patients. Moreover, patients with low miR-299 expression had longer overall survival (OS) compared with those with high miR-299 expression. RNA polymerase II elongation factor, ELL2, was identified as a miR-299 direct target. High expression of ELL2 together with miR-299 down-regulation correlated with a shorter median OS. Conclusions Our results provide the first evidence that ELL2 is a direct target of miR-299 and increased ELL2 expression and down-regulation of miR-299 are associated with GBM progression and poor prognosis in patients, suggesting that ELL2 and miR-299 might have potential prognostic value and be used as tumor biomarkers for the diagnosis of patients with GBM.

Increased Expression of TGFβR2 Is Associated with the Clinical Outcome of Non-Small Cell Lung Cancer Patients Treated with Chemotherapy.

To investigate the prognostic significance of TGFβR2 expression and chemotherapy in Chinese non-small cell lung cancer (NSCLC) patients, TGFβR2 expression NSCLC was analyzed in silico using the Oncomine database, and subsequently analyzed with quantitative RT-PCR in 308 NSCLC biopsies, 42 of which were paired with adjacent non-neoplastic tissues. Our results show that TGFβR2 expression was also increased in NSCLC biopsies relative to normal tissue samples and correlated with poor prognosis. TGFβR2 expression was also significantly correlated with other clinical parameters such as tumor differentiation, invasion of lung membrane, and chemotherapy. Moreover, overall survival (OS) and disease free survival (DFS) was increased in patients with low TGFβR2 expressing NSCLC and who had undergone chemotherapy. Thus, high expression of TGFβR2 is a significant risk factor for decreased OS and DFS in NSCLC patients. Thus, TGFβR2 is a potential prognostic tumor biomarker for chemotherapy.

Upregulation of microRNA-32 is associated with tumorigenesis and poor prognosis in patients with hepatocellular carcinoma

MicroRNA-32 (miR-32) is associated with tumor progression and poor prognosis in certain malignant tumors. However, the function and clinical relevance of miR-32 in human hepatocellular carcinoma (HCC) has not yet been elucidated. The present study aimed to investigate the expression and prognostic value of miR-32 from liver samples in patients with HCC. The expression of miR-32 was analyzed in HCC and healthy tissues using Gene Expression Omnibus datasets. Reverse transcription-quantitative polymerase chain reaction was used to analyze the levels of miR-32 mRNA in 154 HCC liver samples, 33 of which were paired with adjacent non-tumor tissues. The overall survival (OS) rate in patients with HCC was evaluated using Kaplan-Meier survival analysis, and the factors that may affect the prognosis and survival of patients with HCC were analyzed using univariate (log-rank test) and multivariate Cox proportional hazard models. The present results demonstrated that miR-32 expression levels were significantly upregulated in HCC liver biopsies compared with normal tissues (P<0.05). miR-32 expression was significantly associated with the number of foci and tumor diameter (P<0.05). In addition, Kaplan-Meier analysis revealed that patients with low miR-32 expression had longer OS and disease-free survival compared with those with high miR-32 expression (P<0.01). Altogether, to the best our knowledge, the present study is the first study to indicate the association between increased miR-32 expression with HCC progression and poor prognosis in patients. This suggests that miR-32 may have potential prognostic value and may be used as a tumor biomarker for the diagnosis of patients with HCC.

Incidence and physiological mechanism of carboplatin-induced electrolyte abnormality among patients with non-small cell lung cancer

To clarify the association between carboplatin and electrolyte abnormality, a pooled-analysis was performed with the adverse event reports of non-small cell lung cancer patients. A total of 19901 adverse events were retrieved from the FDA Adverse Event Reporting System (FAERS). Pooled reporting odds ratios (RORs) and 95% CIs suggested that carboplatin was significantly associated with hyponatremia (pooled ROR = 1.57, 95% CI 1.182.09, P = 1.99 × 10-3) and hypokalemia (pooled ROR = 2.37, 95% CI 1.803.10, P = 5.24 × 10-10) as compared to other therapies. In addition, we found that dehydration was frequently concurrent with carboplatin therapy (pooled ROR = 2.01, 95% CI 1.522.66, P = 8.37 × 10-7), which may prompt excessive water ingestion and decrease serum electrolyte concentrations. This information has not been mentioned in the FDA-approved drug label and could help explain the physiological mechanism of carboplatin-induced electrolyte abnormality. In conclusion, the above results will facilitate clinical management and prompt intervention of life-threatening electrolyte imbalance in the course of cancer treatment.

Proteogenomic characterization and integrative analysis of glioblastoma multiforme

Glioblastoma multiforme (GBM), the most aggressive and lethal primary brain tumor, is characterized by very low life expectancy. Understanding the genomic and proteogenomic characteristics of GBM is essential for devising better therapeutic approaches.Here, we performed proteomic profiling of 8 GBM and paired normal brain tissues. In parallel, comprehensive integrative genomic analysis of GBM was performed in silico using mRNA microarray and sequencing data. Two whole transcript expression profiling cohorts were used - a set of 3 normal brain tissues and 22 glioma tissue samples and a cohort of 5 normal brain tissues and 49 glioma tissue samples. A validation cohort included 529 GBM patients from The Cancer Genome Atlas datasets. We identified 36 molecules commonly changed at the level of the gene and protein, including up-regulated TGFBI and NES and down-regulated SNCA and HSPA12A. Single amino acid variant analysis identified 200 proteins with high mutation rates in GBM samples. We further identified 14 differentially expressed genes with high-level protein modification, among which NES and TNC showed differential expression at the protein level. Moreover, higher expression of NES and TNC mRNAs correlated with shorter overall survival, suggesting that these genes constitute potential biomarkers for GBM.

Reduced miR-105-1 levels are associated with poor survival of patients with non‑small cell lung cancer

Altered expression of microRNAs (miRNAs or miRs) contributes to lung carcinogenesis. The present study performed an in silico analysis of differentially expressed miRNAs in different peripheral blood samples from patients with various diseases vs. controls using the Gene Expression Omnibus (GEO) database data, and assessed miR-105-1 expression in 32 normal lung and 142 non-small cell lung cancer (NSCLC) tissue samples using reverse transcription-quantitative polymerase chain reaction. Survival data were calculated using Kaplan-Meier curves and a log-rank test. The stepwise forward Cox regression model was performed for univariate and multivariate analyses of independent predictor of overall survival (OS) of patients. The data on in silico and tissue microarray analyses of miRNA expression revealed reduced miR-105-1 expression in different types of human cancer, particularly in NSCLC. The level of miR-105-1 expression was confirmed to be downregulated in NSCLC tissues compared with that in normal lung tissues. Reduced miR-105-1 expression was associated with larger tumor size as well as poor OS and disease-free survival (DFS) of patients. Multivariate survival analysis demonstrated that reduced miR-105-1 expression and tumor size were independent predictors for OS of NSCLC patients. In conclusion, reduced miR-105-1 expression in NSCLC tissues is associated with poor OS and DFS of NSCLC patients.

Protocadherin gamma A7 is down-regulated in colorectal cancer and associated with the prognosis in patients with wild-type KRAS.

Many clustered protocadherin genes (PCDHs) within chromosome 5q31 are frequently down-regulated in colorectal cancer (CRC) due to the hypermethylation of this region, and some of them have been identified as tumor suppressors. However, the association between the expression of the clustered PCDHs and prognosis of CRC patients is still unclear. Here, we identified multiple PCDHs that were significantly down-regulated in CRC by analyzing the RNA-seq data of the Cancer Genome Atlas (TCGA) cohort. Among them, one γ-PCDH subfamily member, PCDHGA7, was found to be associated with overall survival in the patients with wild-type KRAS. Next, we experimentally validated the decrease of PCDHGA7 mRNA and protein levels in tumor tissues of 20 CRC patients by using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry assay (IHC). To further investigate whether the expression of PCDHGA7 could predict clinical outcomes, an independent cohort of 138 patients, whose tumors carried wild-type KRAS, was enrolled. In-house tissue microarrays (TMAs) were developed to facilitate the protein detection, and prognostic significance was analyzed. The result showed low PCDHGA7 expression was associated with advanced TNM stage, high risk of tumor recurrence and short overall survival. In conclusion, this study demonstrates that PCDHGA7 is down-regulated in CRC, and its expression level is correlated with clinical outcomes in patients with wild-type KRAS. Our finding indicates PCDHGA7 could serve as a potential novel biomarker to predict prognosis by combining certain tumor genotypes in patients of CRC.

Reduced miR‑125a levels associated with poor survival of patients with hepatocellular cancer

MicroRNAs (miRNAs) serve an important role in tumorigenesis and development. Although a low expression of miR-125a in hepatocellular carcinoma (HCC) has been reported, the clinical significance remains unknown. In the current study, the data of Gene Expression Omnibus datasets was analyzed and significantly low expression of miR-125a in HCC was verified. Furthermore, the expression and clinical significance of miR-125a was investigated in 27 normal liver and 98 HCC tissue samples using reverse transcription-quantitative polymerase chain reaction analysis. The results demonstrated that the level of miR-125a expression was lower in HCC biopsies compared with that in normal liver tissues. Survival analysis established that miR-125a expression was negatively associated with the prognosis of HCC. Multivariate survival analysis demonstrated that patients with HCC with lowmiR-125a and Ki67-positive expression have shorter overall, and disease-free survival times. Altogether, the results of the current study provide the first evidence that reducedmiR-125a expression is associated with HCC progression and poor prognosis in patients, suggesting that miR-125a may have potential prognostic value as a tumor biomarker for patients with HCC.