Liquid biopsy techniques and lung cancer: diagnosis, monitoring and evaluation.

Lung cancer stands as the most prevalent form of cancer globally, posing a significant threat to human well-being. Due to the lack of effective and accurate early diagnostic methods, many patients are diagnosed with advanced lung cancer. Although surgical resection is still a potential means of eradicating lung cancer, patients with advanced lung cancer usually miss the best chance for surgical treatment, and even after surgical resection patients may still experience tumor recurrence. Additionally, chemotherapy, the mainstay of treatment for patients with advanced lung cancer, has the potential to be chemo-resistant, resulting in poor clinical outcomes. The emergence of liquid biopsies has garnered considerable attention owing to their noninvasive nature and the ability for continuous sampling. Technological advancements have propelled circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), extracellular vesicles (EVs), tumor metabolites, tumor-educated platelets (TEPs), and tumor-associated antigens (TAA) to the forefront as key liquid biopsy biomarkers, demonstrating intriguing and encouraging results for early diagnosis and prognostic evaluation of lung cancer. This review provides an overview of molecular biomarkers and assays utilized in liquid biopsies for lung cancer, encompassing CTCs, ctDNA, non-coding RNA (ncRNA), EVs, tumor metabolites, TAAs and TEPs. Furthermore, we expound on the practical applications of liquid biopsies, including early diagnosis, treatment response monitoring, prognostic evaluation, and recurrence monitoring in the context of lung cancer.

circ_0061265 competitively binds to microRNA-885-3p to promote the development of gastric cancer by upregulating AURKA expression.

BACKGROUND: Circular RNAs (circRNAs) represent a class of newly identified transcripts that act as competing endogenous RNAs (ceRNAs) to modulate gene expression by competing for the shared microRNAs (miRNAs) in humans. In this study, we set out to investigate the role of the circRNA-miRNA-mRNA ceRNA network in gastric cancer (GC). METHODS: A differential analysis on GC-related circRNAs, miRNAs and mRNAs was performed utilizing the R language "limma" package, followed by GO and KEGG enrichment analyses. The Cytoscape visualization software was used to construct the circRNA-miRNA-mRNA ceRNA network. RT-qPCR, Western blot assay, immunohistochemistry, RNA pull down, RIP and dual luciferase gene reporter assay were conducted to verify the expression of the related circRNA, miRNA and mRNA and their interaction in GC tissues and cells. RESULTS: The bioinformatics analysis screened 13 circRNAs, 241 miRNAs and 7483 mRNAs related to GC. Ten DEmRNAs (AURKA, BUB1, CCNF, FEN1, FGF2, ITPKB, CDKN1A, TRIP13, KNTC1 and KIT) were identified from the constructed PPI network and module analysis, among which AURKA was the most critical. A circ_0061265-miRNA-885-3p-AURKA ceRNA network was constructed. In vitro cell experiment demonstrated significantly upregulated circ_0061265 and AURKA, but downregulated miR-885-3p in GC. Moreover, circ_0061265 promoted the occurrence of GC by competitively binding to miRNA-885-3p to regulate AURKA expression. CONCLUSION: Our work validated that circ_0061265 may increase AURKA expression by competitively binding to miRNA-885-3p, thereby promoting GC development.

Design and analysis of a wireless power transfer system for capsule robot using an optimised planar square spiral transmitting coil pair.

BACKGROUND: The wireless power transfer system (WPTS) is a promising way to continuously provide efficient and stable power for gastrointestinal capsule robots with active movement ability. METHODS: The proposed WPTS using an optimised planar square spiral transmitting coil pair with space-saving structure can flexibly adjust the distance between the coils according to the patient's condition, and thus has better applicability. To improve power transfer efficiency and uniformity of the generated magnetic field, design parameters are discussed and optimised based on the analytical calculation and simulation analysis. RESULTS: The power demand can be guaranteed with spacing distance of 350-500 mm and the peak received power of 1124 mW with a remarkable transfer efficiency of 7.8% can be obtained when the spacing reaches the minimum. The human electromagnetic exposure safety in different situations is also discussed and verified. CONCLUSIONS: The WPTS can provide power for capsule robots safely and efficiently.

Comparative analysis of the quantitative parameter method and elasticity color mode method for real-time shear wave elastography in the diagnosis of benign and malignant solid breast lesions.

OBJECTIVE: To examine the performance of real-time shear wave elastography (RT-SWE) in routine clinical practice. METHODS: This was a prospective study of 500 patients. The elasticity color mode method was judged by a four-mode system. The quantitative parameter method was used to measure the modulus of elasticity of the lesions. Pathologic reports were used as a gold standard to comparatively analyze the diagnostic performance of the two methods. RESULTS: A total of 553 tumors were detected. The average mode value and the modulus of elasticity (Emax) of the benign breast masses was lower than that of malignant masses (p < 0.05). With Emax = 67.4 as the diagnostic threshold value, the sensitivity, specificity, accuracy, negative predictive value, and positive predictive value of the two methods were not statistically significant different (p > 0.05). CONCLUSIONS: The shear wave quantitative parameter method and the elasticity color mode method showed similar performances in the diagnosis of benign and malignant breast masses. The elasticity color mode method is convenient and intuitive, whereas the quantitative parameter method can be used to objectively assess the lesions when it is difficult to score the elasticity of an image, but could not be relied on alone.

Gastric cancer with calcifications: A case report.

BACKGROUND: Mucinous gastric carcinoma (MGC) is a rare histological type of gastric carcinoma. Calcifications, seen on imaging and histopathological preparations, and which are infrequent in other types of gastric carcinoma, are characteristic of MGC. We present a patient with MGC with calcifications of the gastric wall and describe the computerized tomography (CT) features of the lesion and changes in the calcifications before and after chemotherapy. CASE SUMMARY: A 61-year-old man was admitted to our hospital in May 2020 because of a large, tender abdominal mass. Abdominal CT showed diffuse, irregular thickening of the gastric walls, with miliary and punctate calcifications. There were metastases to the perigastric and retroperitoneal lymph nodes and also peritoneal seeding. Histological examination of a specimen obtained by endoscopic biopsy showed poorly differentiated calcified signet-ring cell gastric cancer. The patient was clinically staged with T4N+M1 disease. He was treated with docetaxel, cisplatin, and fluorouracil as first-line therapy, irinotecan combined with S-1 as second-line chemotherapy, and programmed cell death protein 1 as third-line therapy. The patient underwent a total of nine cycles of chemotherapy. Follow-up CT scans every 3 mo showed continually increasing calcifications. As of this writing, the patient has survived almost 1 year. CONCLUSION: In this case report, we describe the histopathological and imaging characteristics of a patient with gastric cancer receiving chemotherapy. Multiple punctate calcifications were seen, which gradually increased during chemotherapy. Several possible mechanisms for the calcifications are described, but further research is needed. Future findings may lead to new approaches for the evaluation and treatment of such tumors.

The efficacy and safety of gemcitabine-based induction chemotherapy for locally advanced nasopharyngeal carcinoma treated with concurrent chemoradiation: A meta-analysis.

OBJECTIVES: To assess the efficacy and toxicity of gemcitabine-based induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) in locally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: Both observational studies (OBS) and randomized controlled trials (RCT) were included in the meta-analysis. Systematic online searches were conducted in Web of Sciences, PubMed, Embase, meeting proceedings and ClinicalTrials.gov from the inception to May 25, 2020. The primary endpoint of interest was overall survival. RESULTS: five OBSs and 2 RCTs including 1680 patients were incorporated in the analysis. The evidence from the RCTs showed that adding gemcitabine-based induction chemotherapy to CCRT significantly improved progression free survival (hazard ratio (HR): 0.60, 95% confidence interval (CI): 0.40-0.88; P = .010; chi square P = .25; I2 = 24%) and overall survival (HR: 0.47; 95% CI: 0.28-0.80; P = 0.005; chi square P = .49, I2 = 0%) and was related to a higher risk of hematological toxicities. Furthermore, based on the data of OBSs, overall survival (HR: 0.52; 95% CI: 0.31-0.88; P = .02; chi square P = .37, I2 = 6%) was significantly improved in patients treated with gemcitabine-based induction chemotherapy compared to those treated with taxane-based induction chemotherapy. However, the progression free survival (HR: 0.67; 95% CI: 0.45-1.01; P = .06; chi square P = .74; I2 = 0%) showed no significant difference. CONCLUSIONS: For LA-NPC patients, adding gemcitabine-based induction chemotherapy to CCRT significantly improved overall survival and progression free survival with a higher risk of hematological toxicities when compared to CCRT alone. Also, gemcitabine-based regimen could be used as an alternative induction chemotherapy regimen to taxane-based regimen in the treatment of LA-NPC.

The Utility of Diffusion and Perfusion Magnetic Resonance Imaging in Target Delineation of High-Grade Gliomas.

BACKGROUND: The tumor volume of high-grade glioma (HGG) after surgery is usually determined by contrast-enhanced MRI (CE-MRI), but the clinical target volume remains controversial. Functional magnetic resonance imaging (multimodality MRI) techniques such as magnetic resonance perfusion-weighted imaging (PWI) and diffusion-tensor imaging (DTI) can make up for CE-MRI. This study explored the survival outcomes and failure patterns of patients with HGG by comparing the combination of multimodality MRI and CE-MRI imaging with CE-MRI alone. METHODS: 102 patients with postoperative HGG between 2012 and 2016 were included. 50 were delineated based on multimodality MRI (PWI, DTI) and CE-MRI (enhanced T1), and the other 52 were delineated based on CE-MRI as control. RESULTS: The median survival benefit was 6 months. The 2-year overall survival, progression-free survival, and local-regional control rates were 48% vs. 25%, 42% vs. 13.46%, and 40% vs. 13.46% for the multimodality MRI and CE-MRI cohorts, respectively. The two cohorts had similar rates of disease progression and recurrence but different proportions of failure patterns. The univariate analysis shows that characteristics of patients such as combined with epilepsy, the dose of radiotherapy, the selection of MRI were significant influence factors for 2-year overall survival. However, in multivariate analyses, only the selection of MRI was an independent significant predictor of overall survival. CONCLUSIONS: This study was the first to explore the clinical value of multimodality MRI in the delineation of radiotherapy target volume for HGG. The conclusions of the study have positive reference significance to the combination of multimodality MRI and CE-MRI in guiding the delineation of the radiotherapy target area for HGG patients.

Feedback loop in miR-449b-3p/ADAM17/NF-κB promotes metastasis in nasopharyngeal carcinoma.

An emerging body of evidence has promoted the understanding of the role of microRNAs (miRNAs) in tumorigenesis and progression, but the mediating function of miRNAs in nasopharyngeal carcinoma (NPC) development remains poorly elucidated. In this study, miR-449b-3p was downregulated in NPC specimens (P < .001) and cells (P < .05). Cytological and animal experiments provided evidence that miR-449b-3p inhibited NPC metastasis in vitro and in vivo. Disintegrin and metalloproteinase 17 (ADAM17) was revealed as a direct target of miR-449b-3p. Rescue experiments suggested that the downregulation of ADAM17 in the miR-449b-3p knockdown cells partially reversed the inhibition of cell invasion and migration. Luciferase reporter assay, chromatin immunoprecipitation assay, and Western blot analysis showed that ADAM17 could suppress the promoter activity and expression of miR-449b-3p by inducing NF-κB transcriptional activity. In conclusion, our study provided new insights into the underlying mechanism of the invasion and metastasis of NPC. The novel miR-449b-3p/ADAM17/NF-κB feedback loop could be a target for the clinical treatment of NPC.

Long non-coding RNA LINC01133 mediates nasopharyngeal carcinoma tumorigenesis by binding to YBX1.

Recently, long non-coding RNAs (lncRNAs) have been reported as the vital regulators of various cancers including nasopharyngeal carcinoma (NPC). An increasing number of studies have suggested that lncRNA LINC01133 is dysregulated and involved in human carcinogenesis. However, the roles of LINC01133 in NPC remain largely unknown. In this work, we demonstrated that LINC01133 was significantly downregulated in NPC tissues and cell lines. Loss and gain of function experiments provided evidence that LINC01133 inhibited NPC cell proliferation, invasion and migration both in vitro and in vivo. Besides, Fluorescence in situ hybridization (FISH) assay was performed to determine the localization of LINC01133 and LINC01133 was observed mainly distributed in the nucleus. Importantly, RNA pull-down and RIP assays showed that LINC01133 directly combined with YBX1, and YBX1 can partly reverse the repression of NPC cell proliferation, migration, and invasion caused by LINC01133. Collectively, our exploration indicate that LINC01133 inhibits the malignant-biological behavior of NPC cells by binding to YBX1, thereby suggesting a novel biomarker for the NPC prognosis and treatment.

Identification of key pathways and genes in nasopharyngeal carcinoma using bioinformatics analysis.

Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in the head and neck. The aim of the current study was to identify the key pathways and genes involved in NPC through bioinformatics analysis and to identify potential molecular mechanisms underlying NPC proliferation and progression. Three gene expression profiles (GSE12452, GSE34573 and GSE64634) were downloaded from the Gene Expression Omnibus database. A total of 76 samples were analyzed, of which 59 were NPC samples and 17 were normal samples. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently conducted. The protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed using Cytoscape software. Analysis of GSE12452, GSE34573 and GSE64634 datasets identified 1,301 (553 upregulated and 748 downregulated), 1,232 (348 upregulated and 884 downregulated) and 1,218 (555 upregulated and 663 downregulated) DEGs, respectively. Using Venn diagram analysis, 268 DEGs (59 upregulated and 209 downregulated) that intersected all three datasets, were selected for further analysis. The results of GO analysis revealed that upregulated DEGs were significantly enriched in biological processes, including 'cell adhesion', 'cell division', 'mitosis' and 'mitotic cell cycle'. The downregulated DEGs were mainly enriched in 'microtubule-based movement', 'cilium movement', 'cilium axoneme assembly' and 'epithelial cell differentiation'. The KEGG pathway analysis results revealed that the upregulated DEGs were highly associated with several pathways, including 'extracellular matrix-receptor interaction', 'human papillomavirus infection', 'arrhythmogenic right ventricular cardiomyopathy' and 'focal adhesion', whereas the downregulated DEGs were enriched in 'metabolic pathways', 'Huntington's disease', 'fluid shear stress and atherosclerosis' and 'chemical carcinogenesis'. On the basis of the PPI network of the DEGs, the following top 10 hub genes were identified: Dynein axonemal light intermediate chain 1, dynein axonemal intermediate chain 2, calmodulin 1, coiled-coil domain containing 114, dynein axonemal heavy chain 5, radial spoke head 9 homolog, radial spoke head component 4A, NDC80 kinetochore complex component, thymidylate synthetase and coiled-coil domain containing 39. In conclusion, by performing a comprehensive bioinformatics analysis of DEGs, putative targets that could be used to elucidate the molecular mechanisms underlying NPC were identified.

miR-130a-3p regulated TGF-ß1-induced epithelial-mesenchymal transition depends on SMAD4 in EC-1 cells.

Metastasis and invasion are the primary causes of malignant progression in esophageal squamous cell carcinoma (ESCC). Epithelial-mesenchymal transition (EMT) is crucial step of acquisition of "stemness" properties in tumor cells. However, the mechanism of esophageal cancer metastasis remains unclear. This research was designed to explore the role and mechanism of SMAD4 and miR-130a-3p in the progression of transforming growth factor-ß (TGF-ß)-induced EMT in vivo and in vitro. The expression of miR-130a-3p in ESCC cell line and normal esophageal epithelial cell was determined by RT-qPCR. The protein expression levels of TGF-ß-induced changes in EMT were analyzed by western blotting and immunofluorescence. Dual-luciferase report assays were used to validate the regulation of miR-130a-3p-SMAD4 axis. The effect of miR-130a-3p and SMAD4 in TGF-ß-induced migration, invasion in the ESCC cell line EC-1 was investigated by wound healing assays and Transwell assays. Here we found that knocked down SMAD4 could partially reverse TGF-ß-induced migration, invasion, and EMT progression in the ESCC cell line EC-1. miR-130a-3p, which directly targets SMAD4, is down-regulated in ESCC. miR-130a-3p inhibits the migration and invasion of EC-1 cells both in vitro and in vivo. Finally, miR-130a-3p inhibits TGF-ß-induced EC-1 cell migration, invasion, and EMT progression in a SMAD4-dependent way. In conclusion, this study provides new insights into the mechanism underlying ESCC metastasis. The TGF-ß/miR-130a-3p/SMAD4 pathway could be potential targets for clinical treatment of ESCC.

Comparison analysis between haplo identical stem cell transplantation and matched sibling donor stem cell transplantation for high-risk acute myeloid leukemia in first complete remission.

In order to compare the effect between haploidentical (HID) stem cell transplantation (HSCT) and matched sibling donor (MSD) stem cell transplantation for high-risk acute myeloid leukemia (AML) in first complete remission status (CR1), we retrospectively studied 170 cases who received stem cell transplantation from Jan 2008 to Jul 2015 in Peking University People's Hospital. We divided all cases into MSD group (43 cases) and HID (127 cases) group. Patients in HID and MSD group displayed similar baseline characteristics except for age distribution. There were no statistic differences for overall survival (OS), cumulative incidence of relapse, leukemia free survival (LFS), transplantation related mortality (TRM) between HID and MSD group. The 3-year OS, LFS for all patients was 63.9% and 59.7% respectively. Multivariate analysis showed that grade III-IV acute graft versus host disease (aGVHD) was an independent risk factor for treatment related mortality (HR=8.134, 95% CI: 3.210-20.611, P<0.001), monosomy/complex chromosomal karyotype and white blood cell count more than 50×109 L-1 were two independent factors for relapse (HR=1.533, 95% CI: 1.040-2.260, P=0.031) (HR=1.004, 95% CI: 1.001-1.008, P=0.015). Grade III-IV aGVHD was an independent factor for mortality (HR=3.184, 95% CI: 1.718-5.902, P<0.001). These results demonstrated some risk factors for high-risk AML leukemia transplantation and indicated for AML patients in CR1 status, haplo stem cell transplantation could have the same therapeutic effect as MSD transplantation.

Long noncoding RNA UCA1 promotes the proliferation, invasion, and migration of nasopharyngeal carcinoma cells via modulation of miR-145.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common malignant tumor characterized by highly malignant local invasion and distant metastasis. Recently, increasing attention has been paid to long noncoding RNAs (lncRNAs), which play significant roles in tumorigenesis and progression. However, little is known about the potential role of the lncRNA urothelial carcinoma-associated 1 (UCA1) in NPC cell invasion and migration. METHODS: Real-time quantitative PCR was used to analyze the expression of lncRNA UCA1 in NPC cell lines and NP69. lncRNA UCA1 knock-down nasopharyngeal carcinoma cell line models were established through siRNA. Cell viability was evaluated by Cell counting kit-8 and Colony forming assay. The migration and invasion capacities were evaluated by wound healing and transwell migration and invasion assays. Western blot analysis were used to examine protein changes followed by UCA1 knock-down. RESULTS: Our study confirmed that UCA1 was upregulated in NPC cell lines and involved in NPC tumorigenesis according to our established UCA1-associated competing endogenous RNA network. Moreover, functional analyses indicated that the downregulation of UCA1 exerted inhibitory effects on cell proliferation, invasion, and migration. Mechanistic analyses revealed that UCA1 was the target of miR-145 and functioned as a sponge to repress miR-145 expression. Rescue experiments suggested that lncRNA UCA1 reversed the miR-145-mediated inhibition on oncogene ADAM17 expression, thus promoting the proliferation, invasion, and migration of NPC cells. CONCLUSION: LncRNA UCA1 functions as a tumor promoter in NPC. UCA1 promotes the proliferation and invasion of NPC cells by sponging miR-145, functionally altering ADAM17 expression targeted by miR-145. Our exploration of the underlying mechanism of UCA1 in NPC may provide novel therapeutic targets for NPC.

Progress of preoperative and postoperative radiotherapy in gastric cancer.

BACKGROUND: Gastric carcinoma, a highly common malignant tumor, is treated mainly by surgery. Meanwhile, radiotherapy is attracting increased attention as a crucial locoregional therapy. However, the application of radiotherapy in gastric carcinoma is still limited and radiation standards remain debatable. MAIN BODY: The use of preoperative radiotherapy for treating gastroesophageal junction cancer has advanced. However, additional phase III clinical trials are needed to further verify the therapeutic value of preoperative radiotherapy for gastric cancer. Patients with D1 or D1 plus lymphadenectomy can benefit from postoperative radiotherapy obviously, and postoperative radiotherapy may be effective for patients with D2 lymphadenectomy with a high N stage. The target volume delineation of preoperative and postoperative radiotherapy should be based on clinical experience and the characteristics of lymphatic drainage. CONCLUSIONS: With the advancement of radiotherapy technology, preoperative and postoperative radiotherapy are becoming increasingly accepted as important auxiliary treatments for gastric cancer.

miR-184 Inhibits Tumor Invasion, Migration and Metastasis in Nasopharyngeal Carcinoma by Targeting Notch2.

BACKGROUND/AIMS: A recent study found that dysregulated microRNA-184 (miR-184) is involved in the proliferation and survival of nasopharyngeal carcinoma (NPC). This study aimed to evaluate the detailed mechanisms of invasion, migration and metastasis of NPC cells. METHODS: Quantitative reverse-transcription PCR (qRT-PCR) and Western blot were used to confirm the expression levels of miR-184 and Notch2. NPC cell invasion and migration were subsequently examined using in vitro cell invasion and wound-healing assays, respectively. MicroRNA (miRNA) target gene prediction databases and dual-luciferase reporter assay were adopted to validate the target genes of miR-184. RESULTS: MiR-184 was downregulated in the NPC cell lines. The miR-184 inhibitor increased the number of invading NPC cells, whereas miR-184 mimics inhibited the invasive ability of such cells. The protein level of E-cadherin decreased, whereas those of N-cadherin and vimentin increased in the anti-miR-184 group. This result showed that miR-184 inhibited NPC cell invasion and metastasis by regulating EMT progression. MiRNA target gene prediction databases indicated the potential of Notch2 as a direct target gene of miR-184. Such a notion was then validated by results of dual-luciferase reporter assay. Notably, shRNANotch2 restrained the EMT and partially abrogated the inhibitory effects of miR-184 on EMT progression in NPC cells. CONCLUSION: MiR-184 functions as a tumour-suppressive miRNA targeting Notch2 and inhibits the invasion, migration and metastasis of NPC.

TGF-? regulates the ERK/MAPK pathway independent of the SMAD pathway by repressing miRNA-124 to increase MALAT1 expression in nasopharyngeal carcinoma.

Transforming growth factor beta (TGF-?), a pleiotropic cytokine, promotes cell proliferation and migration in multiple cancers, including nasopharyngeal carcinoma (NPC). microRNA-124 (miR-124) becomes downregulated in NPC and inhibits the tumorigenesis of this disease. However, the role of miR-124 in TGF-?-induced NPC development remains unknown. In this study, constant TGF-? stimulation repressed miR-124 expression, whereas miR-124 overexpression antagonized TGF-?-promoted NPC cell growth and migration. miR-124 overexpression decreased p-SMAD2/3, SMAD4, and p-ERK levels, indicating that ectopic miR-124 overexpression inhibited SMAD and non-SMAD pathways. Pro-oncogenic lncRNA MALAT1 was targeted by miR-124 that regulated ERK/MAPK by targeting MALAT1 independent of the SMAD signaling pathway. In conclusion, our work clarified the significant role of miR-124 in TGF-? signaling pathways independent of the SMAD signaling pathway and showed the potential of miR-124 as a new therapeutic target against NPC.

Prognostic significance of Epstein-Barr virus DNA in NK/T-cell lymphoma: a meta-analysis.

Extranodal NK/T-cell lymphoma is closely associated with Epstein-Barr virus (EBV) infection. However, the prognostic value of EBV-DNA in extranodal NK/T-cell lymphoma remains unclear. Thus, we conducted a meta-analysis to estimate its prognostic significance. PubMed, EMBASE, and Web of Science were used to search for studies conducted until June 12, 2017. The pooled hazard ratio (HR) and its 95% confidence interval (CI) were calculated to evaluate the prognostic value of pretreatment EBV-DNA on the overall survival of extranodal NK/T-cell lymphoma. Seven eligible studies on 356 patients with extranodal NK/T-cell lymphoma were pooled for this meta-analysis. Results suggested that the pretreatment EBV-DNA positivity was significantly correlated with the overall survival of extranodal NK/T-cell lymphoma (pooled HR =3.78, 95% CI: 1.52-9.40, p=0.004; heterogeneity test: I2=52%, p=0.05). Subgroup analyses stratified by sample type, survival analysis mode, and HR origin showed that patients with positive pretreatment EBV-DNA had poorer prognosis than those with negative pretreatment EBV-DNA. Moreover, the cut-off value (HR =1.66; 95% CI: 0.73-3.73; p=0.22) might account for the heterogeneity. No significant publication bias was observed. Pretreatment EBV-DNA positivity can predict poor prognosis for patients with extranodal NK/T-cell lymphoma. Future large-scale studies based on prognostic significance of EBV-DNA for patients with extranodal NK/T-cell lymphoma are necessary.

Down-regulation of miR-517a and miR-517c promotes proliferation of hepatocellular carcinoma cells via targeting Pyk2.

Growing evidence indicates that some tumor suppressive miRNAs are subject to epigenetic modifications during carcinogenesis. Here, we found that a large miRNA cluster of C19MC was upregulated in HCC cells after combined treatment with DNA methylation inhibitor and histone deacetylase inhibitor. MiR-517a and miR-517c were strikingly different from the remaining 41 miRNAs in C19MC. Ectopic expression of MiR-517a and miR-517c inhibited cell proliferation by blocking G2/M transition, whereas down-regulation of miR-517a and miR-517c facilitated cell growth. We further showed Pyk2 is a target of miR-517a and miR-517c and both the miRNAs are downregulated in HCC samples. These data collectively suggest that down-regulation of both miR-517a and miR-517c contribute to HCC development through regulating Pyk2.

Exome sequencing of hepatitis B virus-associated hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and shows a propensity to metastasize and infiltrate adjacent and more distant tissues. HCC is associated with multiple risk factors, including hepatitis B virus (HBV) infection, which is especially prevalent in China. Here, we used exome sequencing to identify somatic mutations in ten HBV-positive individuals with HCC with portal vein tumor thromboses (PVTTs), intrahepatic metastases. Both C:G>A:T and T:A>A:T transversions were frequently found among the 331 non-silent mutations. Notably, ARID1A, which encodes a component of the SWI/SNF chromatin remodeling complex, was mutated in 14 of 110 (13%) HBV-associated HCC specimens. We used RNA interference to assess the roles of 91 of the confirmed mutated genes in cellular survival. The results suggest that seven of these genes, including VCAM1 and CDK14, may confer growth and infiltration capacity to HCC cells. This study provides a view of the landscape of somatic mutations that may be implicated in advanced HCC.

The CFTR polymorphisms poly-T, TG-repeats and M470V in Chinese males with congenital bilateral absence of the vas deferens.

Congenital bilateral absence of the vas deferens (CBAVD) is a frequent cause of obstructive azoospermia, and mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene have also been frequently identified in patients with CBAVD. However, the distribution of the CFTR polymorphisms M470V, poly-T, TG-repeats and F508del mutation in the Chinese CBAVD population with presumed low cystic fibrosis (CF) frequency remains to be evaluated. Samples obtained from 109 Chinese infertile males with CBAVD and 104 normal controls were analyzed for the presence of CFTR (TG)m(T)n, M470V and F508del by PCR amplification followed by direct sequencing. Our study showed that the F508del mutation was not found in our patients. The 5T mutation was present with high frequency in Chinese CBAVD patients and IVS8-5T linked to either 12 or 13 TG repeats was highly prevalent among CBAVD patients (97.22% of 72 cases and 96.91% of 97 alleles with IVS8-5T). Moreover, a statistically significant relationship between TG12-5T-V470 haplotype and CBAVD was detected. This study indicated that the CFTR polymorphisms poly-T, TG-repeats and M470V might affect the process of CBAVD in the Chinese population.