Prognostic Biomarker In Human Cancer Research Articles

Integrated Analysis Reveals That Long Non-Coding RNA TUBA4B Can Be Used as a Prognostic Biomarker in Various Cancers

Background/Aims: Recent studies have reported the importance of tubulin alpha 4b (TUBA4B), a long non-coding RNA, in the development of several cancers; however, studies on its clinical significance are rare. In the present meta-analysis, we investigated whether TUBA4B can be used as a prognostic biomarker in human cancers. Methods: A comprehensive search was performed in PubMed, Embase, Web of Science, and the Gene Expression Omnibus databases. Hazard ratios from individual studies were calculated and pooled using a random-effects or fix-effects model. The pooled hazard ratio (HR) with 95% confidence interval (CI) was used to evaluate the value of TUBA4B. The expression of TUBA4B was evaluated in lung cancer tissue arrays by fluorescence in situ hybridization assay. Additionally, a sensitivity analysis and Begg’s test were conducted. Results: We found that TUBA4B was significantly correlated with overall survival (OS) (HR = 1.33, 95% CI: 1.16–1.52, P=0.000), disease-free survival (DFS; HR = 1.25, 95% CI: 1.06–1.48, P=0.007), and recurrence-free survival (RFS; HR = 1.42, 95% CI: 1.26–1.60, P=0.000). In addition, TUBA4B was a risk factor for lung cancer (HR = 1.24, 95% CI: 1.03–1.49, P=0.021), colon cancer (HR = 1.67, 95% CI: 1.02–2.74, P=0.042), breast cancer (HR = 1.52, 95% CI: 1.10–2.12, P=0.012), and ovarian cancer (HR = 1.67, 95% CI: 1.18–2.36, P=0.004). Moreover, LncRNA-TUBA4B was significantly lower expression in tumor tissues than normal lung tissues (P< 0.001). The expression of lncRNA-TUBA4B was decreased with the progression of lung cancer stage. A subgroup meta-analysis based on data resource, sample size, region, patient numbers, and tumor type was further performed. Our studies revealed that tumor tissues with low levels of TUBA4B was significantly associated with short OS, DFS, and RFS in cancer patients. Conclusion: The present findings suggest that TUBA4B can be a novel biomarker for the prognosis of various cancers.

Long non-coding RNA TUG1 as a potential prognostic biomarker in human cancers: a meta-analysis.

LncRNA taurine upregulated gene 1 (TUG1) is reportedly dysregulated in various cancers. We performed this meta-analysis to clarify the usefulness of TUG1 as a prognostic marker in malignant tumors. The PubMed, Medline, OVID, Cochrane Library, and Web of Science databases were searched from inception to Jan 11, 2017. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to explore the relationship between TUG1 expression and overall survival (OS). Odds ratios (ORs) were calculated to assess the association between TUG1 expression and pathological parameters. Thirteen original studies covering 1,274 cancer patients were included in this meta-analysis. The pooled HR suggested that high TUG1 expression correlated with poor OS (pooled HR=1.41, 95% CI: 1.01-1.98) in cancer types other than non-small cell lung cancer. TUG1 expression was also related to distant metastasis (OR=3.24, 95% CI: 1.18-8.93), large tumor size (OR=4.07, 95% CI: 1.08-15.28) and advanced tumor stage (OR=3.45, 95% CI: 2.19-5.44). Begg’s funnel plot and Egger’s test showed no evidence of obvious asymmetry for overall survival or tumor stage. Thus high TUG1 expression appears predictive of poor OS, distant metastasis, advanced tumor stage and large tumor size. This suggests TUG1 expression could serve as a biomarker for poor prognosis in cancers.

Long non-coding RNA HULC as a potential prognostic biomarker in human cancers: a meta-analysis.

Since the long non-coding RNA HULC (Highly Upregulated in Liver Cancer) is dysregulated in many cancers, we performed a meta-analysis to determine its prognostic potential in malignant tumors. We searched electronic databases, including PubMed, Medline, OVID, Cochrane Library and Web of Science from inception until August 14, 2016 and identified seven studies with 730 cancer patients for the meta-analysis. We analyzed the hazard ratios (HRs) and 95% confidence intervals (CIs) to determine the relationship between HULC expression and overall survival (OS). We also using RevMan5.3 software to calculate odds ratio (ORs) to assess the association between HULC expression and pathological parameters, including lymph node metastasis (LNM), distant metastasis (DM) and the tumor stage. Our analysis showed that higher HULC expression was associated with OS (HR= 0.50, 95% CI: 0.35–0.70, P <0.00001), LNM (OR=0.20, 95 % CI 0.06–0.64), DM (OR=0.27, 95% CI: 0.13–0.54) and the tumor stage (OR=0.39, 95 % CI 0.25–0.64). These meta-analysis data demonstrate that higher HULC expression can be a useful prognostic biomarker in human cancers.

CCAT1: an oncogenic long noncoding RNA in human cancers.

Long noncoding RNAs (lncRNAs) are a new class of noncoding RNAs that participate in a variety of biological processes such as cell proliferation, cell cycle, differentiation and apoptosis, mainly by regulation of gene expression at various levels, including chromatin, splicing, transcriptional and post-transcriptional levels. CCAT1 is a recently identified oncogenic lncRNA, which has been reported to be consistently upregulated in multiple cancer tissues and closely correlated with initiation and progression of cancers. The aim of this paper is to provide an overview of various roles of CCAT1 in human cancers. We searched studies in electronic databases. Studies have shown the high expression pattern and oncogenic role of CCAT1 in different types of cancer, and aberrant expression of CCAT1 is involved in several processes correlated with carcinogenesis such as cell proliferation, apoptosis, migration and invasion by regulating different target genes and pathways. LncRNA CCAT1 promises to be a novel diagnostic biomarker, therapeutic target, as well as prognostic biomarker in human cancers.

SOX4 is a potential prognostic factor in human cancers: a systematic review and meta-analysis.

The aim of the this study was to analyze the status of sex-determining region Y-related high-mobility group box 4 (SOX4) expression in varied human cancers and its correlation with overall survival in patients with human cancers. To observe initially the expression status of SOX4 in twenty kinds of human cancers at protein database (The Human Protein Atlas). We systematically and carefully searched the studies from electronic databases and seriously identified according to eligibility criteria. The correlation between SOX4 expression and overall survival in human cancers was evaluated through Review Manager. We found that SOX4 expression was significantly positive in most types of human cancer tissues, and the positive rate of SOX4 expression was about 78 % in overall cancer tissues. Furthermore, a total of 10 studies which included 1348 cancer patients were included in the final analysis. Meta-analysis showed that SOX4 overexpression was correlated with a poor overall survival and the pooled hazard ratio (HR), and corresponding 95 % confidence interval (CI) was 1.67 (95 % CI 1.01-2.78). From subgroup analyses, we present evidence that SOX4 overexpression was an unfavorable prognostic factor for colorectal cancer patients' recurrence-free survival and gastric cancer patients' overall survival, and the pooled HRs (95 % CI) were 1.73 (95 % CI 1.04-2.88) and 3.74 (95 % CI 1.04-13.45), respectively. In summary, SOX4 is a potential prognostic biomarker in human cancers.

MicroRNAs as tools and effectors for patient treatment in gastrointestinal carcinogenesis.

In the last 20 years, microRNAs (miRNAs) have become the most promising class of diagnostic and prognostic biomarkers for human cancer. From a therapeutic perspective, advances in the understanding of the molecular role of miRNAs in the pathological processes have significantly influenced the selection of new therapeutic modalities. Moreover, the intrinsic characteristics that confer stability to miRNAs in vitro, allow a longer molecular/structural resistance and activity in vivo. Preclinical models have consistently underlined the feasibility and efficacy of miRNA-based therapies, either alone or in combination with current targeted therapies. The appealing strength of such therapeutic option dwells in miRNAs' ability to concurrently target multiple genes, frequently in the context of a specific network/pathway. This property allows miRNA-based therapy to be extremely efficient in regulating distinct biological processes relevant to normal and pathological cell homeostasis. The purpose of this review is to summarize the role of miRNAs in gastrointestinal carcinogenesis and their potential use as novel biomarkers and therapeutics.

Expression profiling of mitochondrial voltage-dependent anion channel-1 associated genes predicts recurrence-free survival in human carcinomas.

BackgroundMitochondrial voltage-dependent anion channels (VDACs) play a key role in mitochondria-mediated apoptosis. Both in vivo and in vitro evidences indicate that VDACs are actively involved in tumor progression. Specifically, VDAC-1, one member of the VDAC family, was thought to be a potential anti-cancer therapeutic target. Our previous study demonstrated that the human gene VDAC1 (encoding the VDAC-1 isoform) was significantly up-regulated in lung tumor tissue compared with normal tissue. Also, we found a significant positive correlation between the gene expression of VDAC1 and histological grade in breast cancer. However, the prognostic power of VDAC1 and its associated genes in human cancers is largely unknown.MethodsWe systematically analyzed the expression pattern of VDAC1 and its interacting genes in breast, colon, liver, lung, pancreatic, and thyroid cancers. The genes differentially expressed between normal and tumor tissues in human carcinomas were identified.ResultsThe expression level of VDAC1 was uniformly up-regulated in tumor tissue compared with normal tissue in breast, colon, liver, lung, pancreatic, and thyroid cancers. Forty-four VDAC1 interacting genes were identified as being commonly differentially expressed between normal and tumor tissues in human carcinomas. We designated VDAC1 and the 44 dysregulated interacting genes as the VDAC1 associated gene signature (VAG). We demonstrate that the VAG signature is a robust prognostic biomarker to predict recurrence-free survival in breast, colon, and lung cancers, and is independent of standard clinical and pathological prognostic factors.ConclusionsVAG represents a promising prognostic biomarker in human cancers, which may enhance prediction accuracy in identifying patients at higher risk for recurrence. Future therapies aimed specifically at VDAC1 associated genes may lead to novel agents in the treatment of cancer.

Duplex value of caveolin-1 in non-small cell lung cancer: a meta analysis

Caveolin-1 (Cav-1) may act as a prognostic biomarker in human cancers. This study is prepared to clarify the prognostic value of Cav-1 in patients with non-small cell lung cancer (NSCLC). All eligible articles from China National Knowledge Infrastructure, Pubmed, Highvire, and Science Direct systems were incorporated into this study. We extracted the patients' clinical characteristics and survival outcomes and performed a meta-analysis to demonstrate the prognostic role of Cav-1 and the correlations between Cav-1 expression and clinical characteristics. Thirteen articles met the inclusion/exclusion criteria. Cav-1 is deregulated in human lung cancers (NSCLC and small cell lung cancer) compared to noncancerous tissues (χ(2)=200.478, p<0.005), but the difference of expression level of Cav-1 is not significant (χ(2)=2.248, p>0.005) among different types of NSCLC, such as adenocarcinomas (ADs), squamous cell carcinoma (SCC) and miscellaneous cancers. Cav-1 expression could predict the poor prognosis of patients with NSCLC. The combined hazard ratio (HR, 95% CI) was 2.00 (1.54, 2.60) for overall survival (OS) and 3.14 (1.68, 5.88) for progression free survival or disease free survival. The combined HR (95% CI) of OS was 2.29 (1.26, 4.17) for ADs and 3.21 (1.69, 6.09) for SCC. The Cav-1 expression was associated with age, differentiation, primary tumor stage, tumor node metastasis stage, lymph node metastasis, chemotherapeutic response, and other clinical characteristics. We also analyzed the odds ratios of Cav-1 expression in AD and SCC patients by subgroups. Cav-1 plays a duplex role in tumorigenesis and tumor progression. Cav-1 may be another biomarker to predict the prognosis of lung cancers.

Abstract LB-353: From worms to humans: understanding the role of microRNAs in cancer progression

Abstract MicroRNAs (miRNAs) regulate important developmental events and are often misexpressed in human cancers, but little is known regarding how these small RNAs contribute to tumor formation. Our laboratory uses a combination of nematode and mammalian model systems to functionally characterize miRNAs and determine the role these factors play in controlling cancer progression pathways. We have successfully used the nematode to analyze how members of the lin-4 and let-7 miRNA families functionally overlap to direct common developmental events associated with cell cycle progression and differentiation. Specifically, animals that carry a triple deletion for the lin-4 homologue, mir-237, and the let-7 homologues, mir-48 and mir-84, exhibit morphological defects and fertility problems related to abnormal mitotic and meiotic abnormalities in the germline that were not found in the single or double deletion combinations. We have also begun to determine how the let-7 miRNA family functions as tumor suppressor genes in mammals. Our experiments showing that exogenous let-7 miRNA administration in the lung using a conditionally activated KRAS lung cancer mouse model result in reduced lung tumor load in these animals highlight the therapeutic potential of miRNAs. We are also studying the role of let-7 together with other miRNA families in directing cancer progression pathways in human tissues of urothelial origin. For instance, we find that let-7 is dysregulated in human prostate cancer cell lines differing in their metastatic status and indicates a novel role for this miRNA in prostate cancer progression. Due to our access to a vast repository of human prostate specimens from the Virginia Prostate Center at Eastern Virginia Medical School, we have begun to analyze the miRNA expression profiles in FFPE specimens taken from the primary prostate tumor, normal adjacent tissue and the lymph node metastasis of individual prostate cancer patients as well as in tumors from patients presenting insignificant and organ confined cancer. We are also determining the “miRNA signatures” in blood, urine, and expressed prostatic secretions (EPS) that were obtained non-invasively from both normal and cancer patients. Our work investigating the role of miRNAs during cancer progression promises to reveal novel therapeutic approaches and diagnostic and prognostic biomarkers for human cancer. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-353.