Nandi Li

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.

The prognostic significance of long noncoding RNAs in non-small cell lung cancer: a meta-analysis

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. The overall 5-year survival rate of patients is extremely low and to find a new marker is urgently needed. Numerous studies indicate that long noncoding RNAs (lncRNAs) abnormally express in cancers. However, the results have been disputed, especially in the aspects of tumor prognosis. Therefore, we performed this meta-analysis to systematically summarize the relationship between lncRNAs expression and NSCLC. A total of 34 eligible studies including 30 on overall survival, 10 on progression-free survival and 23 on clinicopathological features were identified from the databases. Our results indicated that the levels of lncRNAs were associated with the overall survival (OS; hazard ratios [HR], 1.43; 95% confidence interval [95% CI], 1.17-1.76; P < 0.001). However, there was no relationship between lncRNAs and progression-free survival (PFS; hazard ratios [HR], 1.55; 95% confidence interval [95% CI], 0.91-2.63; P = 0.11). Moreover, lncRNAs were related to lymph node metastasis (odds ratios [OR], 1.70; 95% confidence interval [95% CI], 1.03-2.80; P = 0.04), while no association was observed with other characteristics. In conclusion, our present meta-analysis indicated that lncRNAs transcription levels may serve as a promising marker for prognosis of patients with NSCLC.

Prognostic value of abnormally expressed lncRNAs in ovarian carcinoma: a systematic review and meta-analysis

Ovarian cancer (OC) is the most deadly gynecological cancer and it is urgently needed to find a new marker for the progress of OC. Many long noncoding RNAs (lncRNAs) have been reported to be aberrantly expressed in ovarian carcinoma, and may serve as prognostic markers. Therefore, we conducted this meta-analysis to gain a better understanding of the prognostic value of lncRNAs in patients with varian carcinoma. We systematically searched PubMed, EMBASE, and Web of Science. A total of 13 eligible studies, including 10 on clinicopathological features, 13 on prognosis were identified. Pooled hazard ratios (HRs) or odds ratios (OR) and 95% confidence intervals (95% CIs) were calculated using random- or fixed-effects models. Our results revealed that the increased expressions of 8 lncRNAs were associated with poor prognosis and the decreased expressions of 5 lncRNAs were related to poor prognosis in ovarian carcinoma. High HOTAIR expression was associated with shorter overall survival in ovarian cancer (pooled HR: 2.05, 95% CI: 1.51-2.77, P < 0.001). In conclusion, our meta-analysis suggested that LncRNAs could function as potential prognostic markers for ovarian cancer patients and high expression HOTAIR was associated with shorter overall survival in ovarian 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.

Small Nucleolar RNA Host Gene 18 Acts as a Tumor Suppressor and a Diagnostic Indicator in Hepatocellular Carcinoma

Background: Noncoding RNAs are crucial regulators acting as either tumor suppressor genes or oncogenes in human cancer progression. The aberrant expression of noncoding RNAs has been confirmed in different kinds of cancers. Hepatocellular carcinoma is one of the most common malignant tumors worldwide, characterized by insidious onset, great malignancy, and high rates of recurrence and metastasis. Due to lack of early predictive markers, numerous patients are diagnosed in the late stages. As therapeutic options for advanced patients are quite limited, great efforts have been made to screen patients at early stages. A previous study reported that small nucleolar RNA host gene 18 played crucial role in glioma. However, its functions and roles in hepatocellular carcinoma are unknown. Purpose: To explore its functional role and diagnostic value in hepatocellular carcinoma, we investigated its expression level. Methods: We performed real-time quantitative polymerase chain reaction in tumor tissues and adjacent noncancerous tissues derived from patients with hepatocellular carcinoma as well as in plasma, including samples from the healthy control, patients with hepatitis B, cirrhosis, and hepatocellular carcinoma. Results: Small nucleolar RNA host gene 18 was downregulated in liver tissues compared to paired adjacent noncancerous tissues (P < .0001). Meanwhile, plasma small nucleolar RNA host gene 18 showed a relatively high sensitivity and specificity (75.61% and 73.49%) for distinguishing patients with hepatocellular carcinoma whose α-fetoprotein levels were below 200 ng/mL from the healthy controls. Conclusion: Our study suggested that small nucleolar RNA host gene 18 might act as a tumor suppressor gene in hepatocellular carcinoma and potentially a diagnostic indicator to distinguish hepatocellular carcinoma from the healthy control and cirrhosis.

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.

Diagnostic Potential of Differentially Expressed Homer1 and Homer2 in Ischemic Stroke.

Background: Ischemic stroke (IS) is an extremely heterogeneous disease with variable pathogenesis. Due to the lack of early diagnostic marker, the mortality rate of IS remains high worldwide. The family of Homer plays an important role in the pathology of atherosclerotic plaque. In this study, we have investigated its expression pattern and clinical significance in IS. Methods: RT-qPCR was performed to detect the expression of Homer1, Homer2, and Homer3. Results: We found that the mRNA levels of Homer1 (p<0.001) and Homer2 (p<0.001), but not Homer3, in large-artery atherosclerosis (LAA) strokes were significantly upregulated than those in non-LAA strokes and controls. Multinomial logistic regression analyses showed that, although none of the Homer was associated with non-LAA strokes, higher Homer1 (adjusted OR=1.337, 95% CI: 1.227-1.458) and Homer2 (adjusted OR=1.099, 95% CI: 1.062-1.138) levels showed significant associations with increased odds of having LAA stroke, compared with the controls. The receiver operating characteristic (ROC) curves showed that the combination of Homer1 and Homer2 had a better diagnostic accuracy to differentiate LAA strokes from non-LAA strokes and controls, and the sensitivity and specificity ratios were 80.5%/90.4% and 98.0%/70.3%, respectively. Conclusion: Our data suggested that Homer1 and Homer2 might be considered as novel diagnostic biomarkers for LAA stroke.