Integrated Microfluidic-Transistor Sensing System for Multiplexed Detection of Traumatic Brain Injury Biomarkers.

Traumatic brain injury (TBI) is widely recognized as a global public health crisis, affecting millions of people each year, leading to permanent neurologic, emotional, and occupational disability, and highlighting the urgent need for rapid, sensitive, and early assessment. Here, we design a novel and simple lithography-free method for preparing dual-channel graphene-based field-effect transistors (G-FETs) and integrating them with microfluidic channels for simultaneously multiplexed detection of key blood TBI biomarkers: neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP). The G-FET utilizes an ingenious dual-channel electrode array design, where the source is shared between channels and the drains are independent of each other, which is the key to achieving simultaneous output of dual detection signals. At the same time, the microfluidic chip realizes microscale fluidic control and fast sample response time. This integrated detection system shows excellent sensitivity in biological fluids for the TBI biomarkers with detection limits as low as 55.63 fg/mL for NFL and 144.45 fg/mL for GFAP in phosphate-buffered saline (PBS) buffer, respectively. Finally, the clinical sample analysis shows promising performance for TBI detection, with an area under the curve (AUC) of 0.98 for the two biomarkers. And the combined dual-protein assay is also a good predictor of intracranial injury findings on computed tomography (CT) scans (AUC = 0.907). The integrated microfluidic G-FET device with a dual-signal output strategy has important potential for application in clinical practice, providing more comprehensive information for brain injury assessment.

Integrated FET sensing microsystem for specific detection of pancreatic cancer exosomal miRNA10b.

Tumor-derived exosome (TD-Ex) serves as a crucial early diagnostic biomarker of pancreatic cancer (PC). However, accurate identification of TD-Ex from PC is still a challenging work. In this paper, a detection microsystem that integrates magnetic separation and FET biosensor is developed, which is capable of selectively separating TD-Ex of PC from the plasma and detecting exosomal miRNA10b in a sensitive and specific manner. The magnetic beads were functionalized with dual antibody (GPC-1 antibody and EpCAM antibody), enabling selective recognition and capture of PC-derived exosomes. On the other hand, a peptide nucleic acid (PNA)- functionalized reduced graphene oxide field-effect transistor (RGO FET) biosensor was subsequently utilized to detect the exosomal miRNA10b, which is highly expressed in PC- derived exosomes. This system could achieve a low detection limit down to 78 fM, and selectively identify miRNA10b from single-base mismatched miRNA. In addition, 40 clinical plasma samples were tested with this microsystem, and the results indicate that it could effectively distinguish PC patients from healthy individuals. The assay combines specific capture and enrichment of PC-derived exosomes with sensitive and selective detection of exosomal miRNA, showing its potential to be used as an effective scheme for PC early diagnosis.

Protocol for constructing GQD-PMO functionalized FET-biosensor for ultrasensitive exosomal miRNA detection.

Here, we present a protocol for constructing an ultrasensitive biosensor for exosomal-miRNA detection. We describe steps for preparing graphene quantum dot-phosphorodiamidate morpholino oligomer hybrids, depositing them onto the reduced graphene oxide field surface, hybridizing analyte miRNA with the sensor probe, and capturing and calculating electrical signals. We also detail procedures for optimizing biosensor construction and evaluating performance. By quantifying plasma exosomal miRNA21, this protocol can identify cancer patients from healthy individuals. For complete details on the use and execution of this protocol, please refer to Li et al.1.

Homer2 and Homer3 Act as Novel Biomarkers in Diagnosis of hepatitis B virus-induced Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related mortality worldwide. Early detection of HCC can significantly improve patients' outcomes. An increasing number of studies have validated that Homer is dysregulated in cancers and may serve as diagnostic markers. In the present study, we investigated the expression profile and diagnostic significance of Homer2 and Homer3 in hepatitis B virus-induced HCC (HBV-HCC). Methods: Quantitative real-time PCR (QRT-PCR), western blot analysis and immunohistochemistry analysis. Results: Homer2 and Homer3 were downregulated in HCC. The expression of Homer2 was associated with tumor differentiation grade (P= 0.012) and total protein (TP) level (P= 0.032). Homer3 was related to tumor size (P= 0.010), tumor nodes (P= 0.026) and γ-glutamyl transferase (GGT) level (P= 0.001). The receiver operating characteristic curve analyses indicated that the combination of Homer2, Homer3 and AFP possessed a high accuracy (AUC=0.900) to diagnose HCC cases from healthy controls. Conclusion: Our data indicated that Homer2 and Homer3 were downregulated in HCC and might be potential diagnostic marker for HCC.

Combination of CT and telomerase+ circulating tumor cells improves diagnosis of small pulmonary nodules.

BACKGROUNDEarly diagnosis and treatment are key to the long-term survival of lung cancer patients. Although CT has significantly contributed to the early diagnosis of lung cancer, there are still consequences of excessive or delayed treatment. By improving the sensitivity and specificity of circulating tumor cell (CTC) detection, a solution was proposed for differentiating benign from malignant pulmonary nodules.METHODSIn this study, we used telomerase reverse transcriptase-based (TERT-based) CTC detection (TBCD) to distinguish benign from malignant pulmonary nodules < 2 cm and compared this method with the pathological diagnosis as the gold standard. FlowSight and FISH were used to confirm the CTCs detected by TBCD.RESULTSOur results suggest that CTCs based on TBCD can be used as independent biomarkers to distinguish benign from malignant nodules and are significantly superior to serum tumor markers. When the detection threshold was 1, the detection sensitivity and specificity of CTC diagnosis were 0.854 and 0.839, respectively. For pulmonary nodules ≤ 1 cm and 1-2 cm, the sensitivity and specificity of CTCs were both higher than 77%. Additionally, the diagnostic ability of CTC-assisted CT was compared by CT detection. The results show that CT combined with CTCs could significantly improve the differentiation ability of benign and malignant nodules in lung nodules < 2 cm and that the sensitivity and specificity could reach 0.899 and 0.839, respectively.CONCLUSIONTBCD can effectively diagnose pulmonary nodules and be used as an effective auxiliary diagnostic scheme for CT diagnosis.FUNDINGNational Key Research and Development Project grant nos. 2019YFC1315700 and 2017YFC1308702, CAMS Initiative for Innovative Medicine grant no. 2017-I2M-1-005, and National Natural Science Foundation of China grant no. 81472013.

Clinical value and potential mechanisms of LINC00221 in hepatocellular carcinoma based on integrated analysis.

Aims:This study aimed to unveil the functional roles of LINC00221 in hepatocellular carcinoma (HCC). Materials and methods:A discovery cohort and a validation cohort were respectively used to identify and verify the clinical value of LINC00221 in HCC. Bioinformatics analysis was performed to explore its potential mechanisms. Results:LINC00221 was upregulated in HCC tissues and serum samples. Survival analysis and receiver operating characteristic curve further revealed its prognostic and diagnostic roles. Exploration of the mechanism showed that LINC00221 might exert a pro-cancer role via the lncRNA-miRNA-mRNA network.Conclusions: Our study reveals that upregulated LINC00221 can serve as a potential diagnostic and prognostic biomarker and provides novel clues as to the role of LINC00221 in HCC.

Identify and Validate the Transcriptomic, Functional Network, and Predictive Validity of FBXL19-AS1 in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common neoplastic diseases worldwide. Available biomarkers are not sensitive enough for the diagnosis of HCC, hence seeking new biomarkers of HCC is urgent and challenging. The purpose of this study was to investigate the role of F-box and leucine-rich repeat protein 19-antisense RNA 1 (FBXL19-AS1) through a functional network and inquire into its diagnostic and prognostic value in HCC. A comprehensive strategy of genomic data mining, bioinformatics and experimental validation was used to evaluate the clinical value of FBXL19-AS1 in the diagnosis and prognosis of HCC and to identify the pathways in which FBXL19-AS1 might be involved. FBXL19-AS1 was up-regulated in HCC tissues, and its high expression was associated with TNM stage and poor prognosis of HCC patients. The combination of FBXL19-AS1 and alpha-fetoprotein (AFP) in plasma could prominently improve the diagnostic validity for HCC. FBXL19-AS1 might stabilize FBXL19 to reduce the amount of macrophage M1, and then promote the occurrence and development of HCC. Meanwhile, FBXL19-AS1 might participate in regulating HCC related pathways through FBXL19-AS1-miRNA-mRNA network. Our findings indicated that FBXL19-AS1 not only serves as a potential biomarker for HCC diagnosis and prognosis, but also might be functionally carcinogenic.

Role of BCYRN1 in hepatocellular carcinoma pathogenesis by lncRNA-miRNA-mRNA network analysis and its diagnostic and prognostic value.

Aim: This study aimed to excavate the roles of BCYRN1 in hepatocellular carcinoma (HCC). Methods: A comprehensive strategy of microarray data mining, computational biology and experimental verification were adopted to assess the clinical significance of BCYRN1 and identify related pathways. Results:BCYRN1 was upregulated in HCC and its expression was positively associated with both tumor, node, metastasis and worse survival rate in patients with HCC. Through combing plasma BCYRN1 with alpha fetoprotein, the diagnosis of HCC was remarkably improved. BCYRN1 may regulate some cancer-related pathways to promote HCC initiation via an lncRNA-miRNA-mRNA network. Conclusion: Our results propose BCYRN1 as a potential diagnostic and prognostic biomarker and offer a novel perspective to explore the etiopathogenesis of HCC.

Prognostic Role of Tenascin-C for Cancer Outcome: A Meta-Analysis.

BACKGROUND: The prognostic value of tenascin-C in different types of cancers remains controversial. To clarify its prognostic value on overall survival rates, we have conducted a meta-analysis to quantitatively assess the prognostic roles of tenascin-C for patients with cancer. METHODS: We systematically searched all published studies about the role of tenascin-C in cancers on PubMed, Web of Science, Cochrane Library, and Embase. The pooled hazard ratio with 95% confidence intervals was used to analyze the association between tenascin-C expression level and overall survival of patients with cancer. The pooled odds ratio with 95% confidence intervals was used to investigate the association between tenascin-C expression level and clinicopathologic features of patients with cancer. Trial sequential analysis was performed to obtain the required information size. RESULTS: In this meta-analysis, 18 studies including 2732 patients were incorporated. The pooled hazard ratio of 18 trials was 1.73 (95% confidence interval: 1.29-2.32, P < .001) for overall survival, suggesting that elevated tenascin-C expression strongly predicted poor prognosis among patients with various cancers. Simultaneously, elevated tenascin-C expression was also significantly associated with lymph node metastasis (odds ratio = 2.42, 95% confidence interval: 1.79-3.26, P < .001). However, no significant correlation was observed between the tenascin-C expression and distant metastasis (odds ratio = 1.72, 95% confidence interval: 0.86-3.44, P = .127). CONCLUSIONS: Tenascin-C is considered as a promising unfavorable prognostic factor in human cancers. Likewise, tenascin-C can be used as a monitoring indicator for poor prognosis in a wide range of cancers.

circSMAD2 inhibits the epithelial-mesenchymal transition by targeting miR-629 in hepatocellular carcinoma.

BACKGROUND: Circular RNAs (circRNAs) are a class of widely distributed non-coding RNAs, which drew little attention for decades. Recent studies show that circRNAs are involved in cancer progression. METHODS: The circSMAD2 expression in HCC and adjacent non-tumor tissues was measured by quantitative real-time polymerase chain reaction, and the biological function of circSMAD2 was explored by proliferation, apoptosis, migration, invasion, and Western blot assays. Next, the dual-luciferase reporter assay was performed to identify the target miRNA of circSMAD2. Finally, circSMAD2 and its target miRNA were co-transfected in HCC cells to investigate their relationship to HCC progression. RESULTS: In this study, we found that circRNA SMAD2 (circSMAD2) expression was downregulated in hepatocellular carcinoma (HCC) tissues (P = 0.014) compared to the adjacent non-tumor tissues and markedly associated with the differentiation degree of the HCC tissues (P < 0.001). The in vitro experiments showed that overexpressed circSMAD2 inhibited the migration, invasion, and epithelial-mesenchymal transition (EMT) in HCC cells. Bioinformatics predicted that miR-629 is a potential target of circSMAD2, and the dual-luciferase reporter assay verified that miR-629 directly bound circSMAD2. In addition, we found that overexpression of circSMAD2 suppressed the expression of miR-629 in HCC cells, whereas knockdown of circSMAD2 upregulated the expression of miR-629. Furthermore, co-transfection of miR-629 mimics with circSMAD2 reversed the circSMAD2 effects of inhibiting the migration, invasion, and EMT of HCC cells. CONCLUSION: Altogether, our data support that circSMAD2 inhibits the migration, invasion, and EMT of HCC cells by targeting miR-629.

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.

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.

Down-regulation of long non-coding RNA GAS5-AS1 and its prognostic and diagnostic significance in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common solid tumor in global range, with high degree of malignancy and poor prognosis. But the relationship between the expression of GAS5-AS1 and HCC is not documented. This study aimed to profile GAS5-AS1 expression signature and then to explore its clinical significance in HCC. METHODS: Quantitative real-time PCR (RT-qPCR) was performed to detect the expression of GAS5-AS1 in 83 pairs of HCC surgical tissues and adjacent normal liver tissues. We also performed RT-qPCR on plasma samples of 156 patients and 58 healthy controls. RESULTS: We found that GAS5-AS1 was down-regulated in HCC tissues (P< 0.01). Correlation analysis showed that the expression of GAS5-AS1 was notably associated with differentiation (High/Moderate vs Low, P= 0.031), tumor-node-metastasis (TNM) stage (I∼II vs III∼IV, P= 0.020) and glucose levels (< 6.2 vs≧ 6.2, P= 0.047) in HCC patients. The overall survival analysis showed that patients with lower GAS5-AS1 expression had a relatively poor prognosis. Univariate and multivariate analysis elaborated that GAS5-AS1 was an independent prognostic factor for HCC patients. The area under the ROC (AUCROC) demonstrated that GAS5-AS1 presented a high accuracy (AUC = 0.824, 95% CI: 0.741-0.906) for distinguishing HCC from the cirrhosis. When differentiating HCC cases with AFP < 200 ng/ml from the cirrhosis and hepatitis B whose AFP levels were also below 200 ng/ml, GAS5-AS1 had the high sensitivity (89.5%, 89.5%, respectively). CONCLUSIONS: GAS5-AS1 could be considered as a potential prognostic and diagnostic marker in HCC. However, the potential clinical application value of GAS5-AS1 still needs to be further illustrated.

Identification of long non-coding RNA ZFAS1 as a novel biomarker for diagnosis of HCC.

Hepatocellular carcinoma (HCC) is the third major cause of cancer-related deaths. Abundant research show that long non-coding RNAs (lncRNAs) play critical roles in the initiation and progression of HCC and may serve as diagnostic markers for HCC. In the present study, six lncRNAs were chosen as candidate genes on the basis of previous literature to evaluate their diagnostic value on HCC by qRT-PCR. Experiment was first carried out in 22 pairs of tissues from HCC and then those were differently expressed in tissues were further tested in plasma from 20 HCC patients and 20 control cases. At last, ZFAS1 was chosen to be further analyzed in another 214 plasma samples including 79 control cases, 75 hepatitis B and cirrhosis patients, and 60 HCC patients. The levels of plasma ZFAS1 in HCC were significantly higher than those in healthy controls (P<0.001), and in patients with cirrhosis and hepatitis B (P<0.001), and was positively associated with serum α-fetoprotein (AFP). Meanwhile, the area under the receiver operating characteristic curve (AUC) of ZFAS1 was 0.801 to diagnose HCC from healthy controls, while AFP was 0.798 and the combined AUC of ZFAS1 and AFP was 0.891 (95% CI: 0.829-0.953), slightly higher than ZFAS1 alone. In conclusion, our results indicated that ZFAS1 could serve as a biomarker for diagnosing HCC.

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 associations between CYP24A1 polymorphisms and cancer susceptibility: A meta-analysis and trial sequential analysis.

PURPOSE: Published data have shown that vitamin D may have a protective effect on cancer development. CYP24A1, the main enzyme responsible for the degradation of active vitamin D, plays an important role in many cancer related cellular processes. Up to now, relationships between CYP24A1 polymorphisms and cancer susceptibility have been widely investigated, whereas the results are inconsistent. The aim of present meta-analysis was to explore the associations between CYP24A1 polymorphisms and cancer susceptibility. METHODS: We searched on EMBASE, Web of Science, PubMed and China National Knowledge Infrastructure (CNKI) electronic databases (up to July 1, 2017) for relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to make the evaluation clear. RESULTS: Twenty-nine studies published in eight publications involving 20,593 cases and 25,458 controls were included. Five CYP24A1 gene polymorphisms were evaluated: rs2181874, rs2585428, rs4809960, rs6022999, and rs6068816. Our analyses suggested that rs2585428 and rs4809960 polymorphisms were significantly associated with overall cancer risk. Stratification analyses of ethnicity indicated that rs2585428 and rs4809960 polymorphisms decreased the risk of cancer among Caucasians. When studies were stratified by cancer type, our results indicated that rs2585428 significantly decreased the risk of pancreas cancer, while rs4809960 significantly decreased the risk of breast cancer. There were no associations of rs2181874, rs6022999, or rs6068816 with overall cancer risks. CONCLUSION: Associations between CYP24A1 polymorphisms and cancer risks were examined, and additional multi-center studies with large samples are necessary to validate our results.

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.

Association between 8q24 rs6983267 polymorphism and cancer susceptibility: a meta-analysis involving 170,737 subjects.

Published data on the association between 8q24 rs6983267 polymorphism and cancer risk are inconsistent. Thus, we conducted a meta-analysis to evaluate the relationship between rs6983267 polymorphism and cancer risk. We searched on PubMed, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI) up to November 1, 2016 for relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of this association. We included 78 case-control studies with a total of 73,996 cases and 96,741 controls in this meta-analysis. The pooled results showed that rs6983267 polymorphism was significantly associated with increased risk of overall cancer in all genetic models (dominant model: OR = 1.19, 95% CI = 1.13-1.26; recessive model: OR = 1.19, 95% CI = 1.14-1.25; homozygous model: OR= 1.31, 95% CI = 1.23-1.40; heterozygous model: OR = 1.14, 95% CI = 1.10-1.19; allelic model: OR = 1.14, 95% CI = 1.11-1.18). Stratified analyses indicated that rs6983267 significantly increased the risk of colorectal cancer in Caucasians, prostate cancer in Caucasians and Asians, thyroid cancer in Caucasians and lung cancer in Asians. When studies were stratified by study quality, source of controls and genotyping method, significant associations were especially found in the high quality studies, the publication-based studies, the hospital-based studies, and the PCR-RFLP studies. Additional well-designed studies with large samples should be performed to validate our results.

Identification of long non-coding RNA 00312 and 00673 in human NSCLC tissues.

Non-small cell lung cancer (NSCLC) is a fatal disease to human health. Despite the advanced progresses in cancer therapy during the past decades, NSCLC still remains the leading cause of cancer death worldwide. The long non­coding RNAs (lncRNAs) recently have been considered as key regulators of tumor malignant. Previous studies identified that long non­coding RNAs, linc00312 and linc00673 are markedly associated with lung cancer. However, current understanding of the two lncRNAs involving in NSCLC remains unclear. The aim of the present study was to profile their expression and clinicopathological significance in 76 patients' NSCLC tissues compared to non­tumor tissues using reverse transcription-quantitative polymerase chain reaction. Data have indicated that the linc00312 expression level was significantly decreased in NSCLC tissues (P<0.001), while a higher linc00673 level has been detected in the same tumor tissues (P<0.01). In addition, the low expression of linc00312 was associated with the Tumor­Node­Metastasis stage of NSCLC (P<0.05), whereas the high expression of linc00673 was related with the histological types of NSCLC (P<0.05). In conclusion, lncRNA 00312 and 00673 may serve as potential novel biomarkers for lung cancer early diagnosis, which may play a vital role in treatments of NSCLC.

Identification of circulating long non-coding RNA GAS5 as a potential biomarker for non-small cell lung cancer diagnosisnon-small cell lung cancer, long non-coding RNA, plasma, GAS5, biomarker.

Non-small cell lung cancer (NSCLC) is one of the most malignant cancers in the world. Early diagnosis of NSCLC has become especially important for patient treatment and prognosis. Increasing evidence suggest that long non-coding RNA GAS5 plays vital roles in cancer proliferation and differentiation in NSCLC. However, its clinical value in the diagnosis of NSCLC is unclear. The objective of this study was to evaluate the importance of circulating GAS5 as a biomarker for NSCLC diagnosis. In our study, quantitative real-time PCR (QRT-PCR) was applied to detect the GAS5 expression level in 80 pairs of cancer tissues and 57 pairs of plasma samples of NSCLC patients. Further analysis was performed to study the differential expression of circulating GAS5 in 111 NSCLC patients and 78 healthy controls in our study. The results showed that GAS5 decreased in NSCLC tissues compared to noncancerous tissues (P<0.001). Furthermore, the GAS5 expression level was statistically declined in early stage of NSCLC before surgery compared with healthy controls (P<0.05) and sharply increased in postoperative groups (P=0.026). ROC curve analysis for early stage of NSCLC with the combination of GAS5, CEA and CA199 showed that the area under the ROC curve (AUC) was 0.734 (95% CI, 0.628­0.839; P<0.0005). In conclusion, circulating GAS5 could be functioned as a potential combined biomarker for screening NSCLC and patient monitoring after surgical treatment.