Man Zhu

Identification of Circulating Long Noncoding RNA HOTAIR as a Novel Biomarker for Diagnosis and Monitoring of Non–Small Cell Lung Cancer

Long noncoding RNA (LncRNA) homeotic genes (HOX) transcript antisense RNA (HOTAIR) has been reported to play a vital role in various cancers. It has been found that HOTAIR was upregulated in non–small cell lung cancer (NSCLC) and involved in cell invasion and metastasis. The aberrant expression of HOTAIR is expected to serve as a potential biomarker for patients with NSCLC. Our aim in this study was to detect the plasma levels of HOTAIR and further evaluate its diagnostic value for NSCLC. The levels of HOTAIR were measured in 105 patients with NSCLC and 80 healthy controls by quantitative real-time polymerase chain reaction. The results indicated that plasma HOTAIR levels were higher in NSCLC than in healthy controls. Besides, plasma HOTAIR levels were associated with histology subtype (P = .039) and tumor-node-metastasis stage (P = .022). The ROC curves showed that plasma HOTAIR has high diagnostic accuracy for NSCLC, and the area under curve (AUC) for NSCLC versus healthy was 0.791 (95% CI: 0.727-0.855) which was higher than carcinoembryonic antigen (CEA) (AUC = 0.737, 95% CI: 0.666-0.808). Moreover, the combination of HOTAIR and CEA could provide a more accurate diagnosis than HOTAIR or CEA alone (AUC = 0.841, 95% CI: 0.783-0.898). Plasma HOTAIR levels were significantly lower in postoperative samples than in preoperative samples. Plasma HOTAIR could serve as a promising biomarker for diagnosing and monitoring NSCLC.

Identification of Circulating Long Noncoding RNA Linc00152 as a Novel Biomarker for Diagnosis and Monitoring of Non-Small-Cell Lung Cancer

Objective Long noncoding RNAs (lncRNAs) have been reported to play vital roles in non-small-cell lung cancer (NSCLC). Recently, long noncoding RNA Linc00152 has been reported to play important roles in various cancers. In this study, our aim was to investigate its expression pattern and clinical significance and further evaluate its diagnostic value for NSCLC. Methods The levels of Linc00152 were detected in NSCLC tissues and plasma samples by quantitative real-time PCR (qRT-PCR). Receiver operating characteristic (ROC) curves were depicted to evaluate the diagnostic value. Results We found that Linc00152 levels were upregulated in both NSCLC tissues and plasma samples. Plasma Linc00152 levels were significantly lower in postoperative samples than in preoperative samples. Besides, high Linc00152 expression was significantly correlated with tumor size (r = 0.293, P = 0.005) and tumor stage (r = 0.324, P = 0.011). The ROC curves indicated that plasma Linc00152 has high diagnostic accuracy for NSCLC, and the area under curve (AUC) for NSCLC versus healthy was 0.816 (95% CI: 0.757–0.875). Moreover, we found that the combination of Linc00152 and CEA could provide a more powerful diagnosis efficiency than Linc00152 or CEA alone (AUC = 0.881, 95% CI: 0.836–0.926). Conclusions Plasma Linc00152 could serve as a promising biomarker for diagnosing and monitoring NSCLC.

Peripheral Blood Leukocyte Expression of lncRNA MIAT and Its Diagnostic and Prognostic Value in Ischemic Stroke

BACKGROUND Ischemic stroke (IS) is an extremely heterogeneous disease with variable pathogenesis. Due to the lack of early diagnostic markers, the mortality rate of IS remains high. Cumulative evidence shows that long noncoding RNAs among noncoding RNAs play important roles in cardiovascular diseases. In the present study, we focused on the expression pattern of myocardial infarction-associated transcript (MIAT) and its clinical significance in IS. METHODS Blood samples were obtained from IS patients (n = 189) and healthy controls (n = 189). The National Institutes of Health Stroke Scale (NIHSS) was measured at the time of admission. Short-term functional outcome was measured by the modified Rankin Scale (mRS) at 3 months after admission. Multivariate analyses were performed using logistic regression models. The receiver operating characteristic (ROC) curve was used to evaluate the accuracy of MIAT in the diagnosis and prognosis of IS. RESULTS In IS patients, MIAT expression level was significantly upregulated and correlated with NIHSS scores (r = .421, P <.001), mRS (r = .339, P <.001), high-sensitivity C-reactive protein (r = .309, P <.001), and infarct volume (r = .318, P <.001). ROC curves indicated that MIAT could serve as a potential marker for discriminating IS patients from the controls with an area under the curve of .842 (95% confidence interval, .802-.881). The overall survival analysis showed that patients with higher MIAT expression had a relatively poor prognosis. Meanwhile, the multivariate analysis revealed that MIAT was an independent prognostic marker of functional outcome and death in patients with IS. CONCLUSION Our data suggested that MIAT might be a potential diagnostic and prognostic indicator in IS.

Plasma miR-92a-2 as a biomarker for small cell lung cancer

MicroRNAs (miRNAs) are small, non-coding RNAs that play important roles in the carcinogenesis and progression of cancers. Aberrant expression of miRNAs in tissue and plasma has been found in various solid tumors. Our research aims to determine whether the abnormal plasma miRNA expression patterns can be used as a predictive marker for the diagnosis and prognosis of small cell lung cancer (SCLC). Fifty SCLC patients and 30 healthy controls annotated with clinical characteristics and specific questionnaire survey for smoking history were available. Quantification of several miRNAs (miR-20a-5p, miR-92a-2-5p and miR-17-5p) was performed using quantitative real-time polymerase chain reaction (qRT-PCR), and results were analyzed using SPSS statistics 17.0. Plasma miR-92a-2 level was significantly higher in the SCLC patients group compared with healthy control (P< 0.0001), the receiver operating characteristic (ROC) curve analysis showed that the specificity and sensitivity were at 100% and 56% for diagnosis of SCLC, area under the ROC curve (AUC) was 0.761. No other statistically significant differences were found in the expression level of plasma miR-92a-2 among survival analysis in SCLC. Detection of miR-92a-2 levels in plasma could be a potential and noninvasive method for the diagnosis of SCLC.

Prognostic and Diagnostic Significance of SDPR-Cavin-2 in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is a malignant tumor worldwide. Due to the lack of early prediction marker, numerous patients were diagnosed in their late stage. The family of cavins plays important roles in caveolae formation and cellular processes. Cavin-2, one of the members of cavins, has been reported as a suppresser in cancers. In this study, we have investigated its expression pattern and clinical significance in HCC. Methods: RT‑qPCR was performed to detect the expression of cavin-2. Results: Cavin-2 was down-regulated in HCC and associated with tumor differentiation (r=-0.275, P=0.013) and tumor-node-metastasis (TNM) stage (r=-0.216, P=0.035). The Overall survival analysis showed that patients with lower cavin-2 expression had a relatively poor prognosis. Meanwhile, the multivariate analysis revealed that cavin-2 was an independent prognostic factor. The receiver operating characteristic curve analyses indicated that plasma cavin-2 presented a high accuracy (AUC=0.727, 0.865, 0.901) for diagnosing HCC cases from controls, hepatitis B and cirrhosis patients, respectively. Meanwhile, plasma cavin-2 showed a high sensitivity (88.4%, 89.9%) for detecting HCC with the serum α‑fetoprotein (AFP) levels below 200 ng/ml from those hepatitis B and cirrhosis cases. Conclusion: Our data suggested that cavin-2 might be considered as a potential prognostic and diagnostic indicator in HCC.

The Circular RNA hsa_circ_0001445 Regulates the Proliferation and Migration of Hepatocellular Carcinoma and May Serve as a Diagnostic Biomarker

Circular RNAs (circRNA), a class of noncoding RNAs, have been found to be involved in various diseases. Here, the expression levels of the circRNA hsa_circ_0001445 in 73 pairs of hepatocellular carcinoma (HCC) and adjacent nontumor tissues were investigated by quantitative real-time polymerase chain reaction (qRT-PCR). Our data demonstrate that the hsa_circ_0001445 levels were significantly decreased in HCC tissues (P < 0.001) and markedly associated with the number of tumor foci (P = 0.014). Furthermore, in vitro approaches showed that overexpression of hsa_circ_0001445 promoted apoptosis and inhibited proliferation, migration, and invasion of HCC-derived cells, suggesting that hsa_circ_0001445 might be involved in the development of HCC. In addition, we found that the plasma hsa_circ_0001445 transcription levels in HCC patients were lower than those in cirrhosis (P < 0.001) and hepatitis B (P < 0.001) patients as well as in healthy controls (P < 0.001). In fact, receiver operating characteristic curve analysis indicated that plasma hsa_circ_0001445 could be a fairly accurate marker to distinguish HCC cases from healthy controls as well as patients with cirrhosis or hepatitis B.

Inhibition of miR-155, a therapeutic target for breast cancer, prevented in cancer stem cell formation

BACKGROUND Breast cancer is a common cancer in women of worldwide. Cancer cells with stem-like properties played important roles in breast cancer, such as relapse, metastasis and treatment resistance. Micro-RNA-155 (miR-155) is a well-known oncogenic miRNA overexpressed in many human cancers. METHODS The expression levels of miR-155 in 38 pairs of cancer tissues and adjacent normal tissues from breast cancer patients were detected using quantitative real-time PCR. The invasive cell line MDA-MB-231 was used to quantify the expression of miR-155 by tumor-sphere forming experiment. Soft agar colony formation assay and tumor xenografts was used to explore whether the inhibition of miR-155 could reduce proliferation of cancer cells in vivo and vitro. RESULTS In the study, we found miR-155 was upregulated in BC. Soft agar colony formation assay and tumor xenografts showed inhibition of miR-155 could significantly reduce proliferation of cancer cells in vivo and vitro, which confirmed that miR-155 is an effective therapeutic target of breast cancer. Sphere-forming experiment showed that overexpression of miR-155 significantly correlated with stem-like properties. Expressions of ABCG2, CD44 and CD90 were repressed by inhibition of miR-155, but CD24 was promoted. Interestingly, inhibition of miR-155 rendered MDA-MB-231 cells more sensitive to Doxorubicinol, which resulted in an increase of inhibition rate from 20.23% to 68.72%. Expression of miR-155 not only was a therapeutic target but also was associated with cancer stem cell formation and Doxorubicinol sensitivity. CONCLUSIONS Our results underscore the importance of miR-155 as a therapeutic target and combination of Doxorubicinol and miR-155-silencing would be a potential way to cure breast cancer.

Decreased expression of LncRNA SRA1 in hepatocellular carcinoma and its clinical significance

BACKGROUND Hepatocellular carcinoma (HCC), is an extremely aggressive malignancy with poor prognosis and high fatality rates worldwide. Accumulating evidence indicated that novel biomarkers are required to get a better understanding of the biological mechanisms of HCC. SRA1, a long non-coding RNA (lncRNA), serves as a critical regulator in several cancers. However, the association between SRA1 expression and tumorigenesis in HCC tissues remains unclear. OBJECTIVE In the present study, we evaluated the expression of SRA1 in HCC and its clinical association. METHODS The expression levels of SRA1 in 67 pairs of cancer tissues and adjacent normal tissues from HCC patients were detected using quantitative real-time PCR. Expression of SRA1 in HCC cell lines compared with normal human hepatocyte cell lines was also measured. Finally, the potential associations between its level in HCC tissues and the clinicopathological parameters were analyzed as well. RESULTS The results indicated that the expression levels of SRA1 in HCC were remarkably decreased, compared with matched normal tissues (P< 0.001). Levels of SRA1 in HCC cell lines were also significantly decreased than that in normal human hepatocyte cell line L-02. Additionally, the levels of SRA1 were significantly associated with tumor size (P= 0.020) and serum GLU level (P= 0.046). CONCLUSIONS This study highlighted that SRA1 was downregulated in HCC and might serve as a tumor suppressor in HCC, which laid a solid foundation for future research.

Long non-coding RNA XIST predicts worse prognosis in digestive system tumors: a systemic review and meta-analysis

Increasing studies are indicating that long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is associated with the prognosis of cancer patients. However, the results have been disputed. Therefore, we aimed to further explore the prognostic value and clinical significance of XIST in various types of cancers. Then, we focussed our research on the comparison of the predictive value of XIST between digestive system tumors and non-digestive system tumors. We performed a systematic search by looking up PubMed, Embase, Cochrane Library, Web of Science, and Medline (up to 3 January 2018). Fifteen studies which matched our inclusion criteria with a total of 920 patients for overall survival and 867 patients for clinicopathological characteristics were included in this meta-analysis. Pooled hazard ratios (HR) and odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) were calculated to summarize the effects. Our results suggested that high expression levels of XIST were associated with unfavorable overall survival in cancer patients (pooled HR = 1.81, 95% CI: 1.45–2.26). Additionally, we found that XIST was more valuable in digestive system tumors (pooled HR = 2.24, 95% CI: 1.73–2.92) than in non-digestive system tumors (pooled HR = 1.22, 95% CI: 0.60–2.45). Furthermore, elevated expression levels of XIST were connected with distant metastasis and tumor stage. XIST was correlated with poor prognosis, which suggested that XIST might serve as a novel predictive biomarker for cancer patients, especially for patients of digestive system tumors.

Clinical and Diagnostic Significance of Homer1 in hepatitis B virus-induced Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is a malignant tumor worldwide. Attributed to the lack of early diagnosis index, most patients are diagnosed in their late stage. Homer1, as a member of scaffold protein family, is made up of two different isoforms: Homer1a and Homer1b/c. More and more evidences show that Homer1 is dysregulated in cancers. Here, in this study, we investigated the expression profile, clinical, diagnostic and prognostic significance of Homer1 in hepatitis B virus-induced HCC (HBV-HCC). Methods: We first tested the expression of Homer1 in HCC cell lines by quantitative real-time PCR (qRT-PCR), western blot. Then, 86 pairs of tumorous and adjacent normal tissues from HCC together with a total number of 245 peripheral blood samples were enrolled to check the expression levels of Homer1 by quantitative real-time PCR (qRT-PCR). Results: The results revealed that the levels of Homer1 were both downregulated in HCC cell line and tissue and were associated with tumor size, but were not related to the prognosis of HBV-HCC. Receiver-operating characteristic curve analyses indicated that the sensitivity of Homer1 to differentiate HCC patients from the controls was high to 100.0% and the combination of Homer1 and AFP got a higher prediction value of HCC (AUC=0.890). Conclusion: Our data highlighted that Homer1 played a critical role in HCC tumorigenesis and might be a potential diagnostic marker for HCC.