Overexpression of UBE2C in esophageal squamous cell carcinoma tissues and molecular analysis.

BACKGROUND: Esophageal cancer is a common malignant tumor and its 5-year survival rate is much lower than 30% due to its invasiveness and pronounced metastasis ability, as well as the difficulty in early diagnosis. This study aimed to elucidate the molecular mechanism of ubiquitin conjugating enzyme E2 C (UBE2C) in esophageal squamous cell carcinoma (ESCC). METHODS: In this study, we conducted a comprehensive evaluation of the UBE2C expression in ESCC by collecting the protein and mRNA expression data (including in-house RNA-seq, in-hosue immunohistochemistry, TCGA-GTEx RNA-seq and tissue microarray) to calculate a combined standardized mean difference (SMD) and summary receiver operating characteristic curve (sROC). Kaplan-Meier (K-M) method was used for survival analysis. We also explored the mechanism of UBE2C in ESCC by combing the differentially expressed genes (DEGs) of ESCC, related-genes of UBE2C in ESCC and the putative miRNAs and lncRNAs which may regulate UBE2C. RESULTS: UBE2C protein and mRNA were highly expressed in ESCC tissues (including 772 ESCC tissue samples and 1837 non-cancerous tissue control samples). The pooled SMD of UBE2C expression values was 1.98 (95% CI: 1.51-2.45, p < 0.001), and the the area under the curve (AUC) of the sROC was 0.93 (95% CI: 0.90-0.95). The results of survival analysis suggested that UBE2C is likely to play different roles in different stages of the ESCC. Pathway anaylsis showed that UBE2C mainly influenced the biological function of esophageal cancer by synergistic effects with CDK1, PTTG1 and SKP2. We also constructed a potential UBE2C-related ceRNA network for ESCC (HCP5/has-miR-139-5p/UBE2C). CONCLUSION: UBE2C mRNA and protein level were highly expressed in ESCC and UBE2C was likely to play different roles in different stages of the ESCC.

Imaging features of hemangioma in long tubular bones.

BACKGROUND: To investigate the imaging features of hemangiomas in long tabular bones for better diagnosis. METHODS: Twenty-four patients with long bone hemangiomas confirmed by pathology were enrolled. Nineteen patients had plain radiography, fourteen patients had computed tomography (CT) and eleven had magnetic resonance imaging (MRI). The hemangioma was divided into medullary [13], periosteal [6] and intracortical type [5]. RESULTS: Among 19 patients with plain radiography, eleven patients were medullary, three periosteal, and five intracortical. In the medullary type, the lesion was primarily osteolytic, including five cases with irregular and unclear rims and one lesion having osteosclerotic and unclear rims. In three patients with the periosteal type, the lesion had clear rims with involvement of the cortical bone in the form of bone defect, including two cases with local thickened bone periosteum and one case having expansile periosteum. Five intracortical hemangiomas had intracortical osteolytic lesions with clear margins. Among 14 patients with CT imaging, 8 cases were medullary, three periosteal, and three intracortical. Among 8 medullary hemangiomas, one had ground glass opacity, and seven had osteolytic, expansile lesions like soft tissue density with no calcification. In three periosteal cases, the lesion was osteolytic with thickened periosteum and narrowed medullary cavity. In three intracortical hemangiomas, the lesion was of even soft tissue density with no calcification. Among 11 patients with MRI imaging, seven were medullary, two periosteal, and two intracortical. Among 7 medullary lesions, six were of hypointense signal on T1WI and hyperintensesignal on T2 WI. In two periosteal cases, the periosteum was thickened, with one case being of equal signal, and the other having no signal. Two intracortical hemangiomas were both of slightly low signal on T1WI but hyperintense signal on T2WI. CONCLUSIONS: The long bone hemangiomas had characteristic cystic honeycomb-like presentations in plain radiograph. CT and MRI imagings are helpful for diagnosis of hemangiomas in long bone.

The clinical significance of endothelin receptor type B in hepatocellular carcinoma and its potential molecular mechanism.

OBJECTIVE: To explore the clinical significance and potential molecular mechanism of endothelin receptor type B (EDNRB) in hepatocellular carcinoma (HCC). METHODS: Immunohistochemistry was used to detect EDNRB protein expression level in 67 HCC paraffin embedded tissues and adjacent tissues. Correlations between EDNRB expression level and clinicopathologic parameters were analyzed in our study. The expression level and clinical significance of EDNRB in HCC were also evaluated from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The cBioPortal for Cancer Genomics was employed to analyze the EDNRB related genes, and Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and Protein-Protein Interaction (PPI) network were conducted for those EDNRB related genes. RESULTS: Lower expression level of EDNRB in HCC was verified by immunohistochemistry than adjacent tissues (P < 0.0001). The expression level of EDNRB in HCC tissues was lower than normal control liver tissues based on TCGA and GEO data (standard mean difference [SMD] = -1.48, 95% [confidence interval] CI: -1.63-(-1.33), Pheterogeneity = 0.116, I2 = 32.4%). Kaplan-Meier analysis showed that HCC patients with lower EDNRB expression were more prone to poor prognosis (P = .0041). The top terms of GO annotation in biological process, cellular component and molecular function were vasculature development, actin filament and transmembrane receptor protein kinase activity, respectively. The KEGG pathway enrichment analysis confirmed that EDNRB related genes mainly participated in Vascular smooth muscle contraction, cGMP-PKG signaling pathway and Focal adhesion pathways. The result of PPI network construction showed that KDR, VEGFC, FLT1, CDH5 and ADCY4 were possible to become the core genes of EDNRB related genes, which need further experiments to confirm. CONCLUSION: Our study provides novel findings and insights on the molecular pathogenesis of HCC from EDNRB view.

High peak power 2.8 µm Raman laser in a methane-filled negative-curvature fiber.

We demonstrate a 2.8 µm gas Raman laser in a methane-filled hollow-core negative-curvature fiber with average power of 113 mW, pulse energy of 113 µJ and estimated peak power of 9.5 MW. Raman quantum efficiency of 40% has been reached from the pump source at 1.064 µm to the 2nd order vibrational Stokes at 2.812 µm using 1.8 MPa methane gas. To our knowledge, this is the first high peak power fiber-based gas Raman laser in mid-infrared region and a range of applications in supercontinuum generation, laser surgery, molecular tracing and gas detection are in prospect.

The suppressive role of miR-542-5p in NSCLC: the evidence from clinical data and in vivo validation using a chick chorioallantoic membrane model.

BACKGROUND: Non-small cell lung cancer (NSCLC) has led to the highest cancer-related mortality for decades. To enhance the efficiency of early diagnosis and therapy, more efforts are urgently needed to reveal the origins of NSCLC. In this study, we explored the effect of miR-542-5p in NSCLC with clinical samples and in vivo models and further explored the prospective function of miR-542-5p though bioinformatics methods. METHODS: A total of 125 NSCLC tissue samples were collected, and the expression of miR-542-5p was detected by qRT-PCR. The relationship between miR-542-5p level and clinicopathological features was analyzed. The effect of miR-542-5p on survival time was also explored with K-M survival curves and Cox's regression. The effect of miR-542-5p on the tumorigenesis of NSCLC was verified with a chick chorioallantoic membrane (CAM) model. The potential target genes were predicted by bioinformatics tools, and relevant pathways were analyzed by GO and KEGG. Several hub genes were validated by Proteinatlas. RESULTS: The expression of miR-542-5p was down-regulated in NSCLC tissues, and consistent results were also found in the subgroups of adenocarcinoma and squamous cell carcinoma. Down-regulation of miR-542-5p was found to be connected with advanced TNM stage, vascular invasion, lymphatic metastasis and EGFR. Survival analyses showed that patients with lower miR-542-5p levels had markedly poorer prognosis. Both tumor growth and angiogenesis were significantly suppressed by miR-542-5p mimic in the CAM model. The potential 457 target genes of miR-542-5p were enriched in several key cancer-related pathways, such as morphine addiction and the cAMP signaling pathway from KEGG. Interestingly, six genes (GABBR1, PDE4B, PDE4C, ADCY6, ADCY1 and GIPR) from the cAMP signaling pathway were confirmed to be overexpressed in NSCLCs tissues. CONCLUSIONS: This evidence suggests that miR-542-5p is a potential tumor-suppressed miRNA in NSCLC, which has the potential to act as a diagnostic and therapeutic target of NSCLC.

Multiple plexiform schwannomas in the plantar aspect of the foot: case report and literature review.

BACKGROUND: Plexiform schwannoma (PS) is a rare, peripheral nerve sheath tumor arranged in a plexiform pattern. CASE PRESENTATION: We report an unusual case of a 19-year-old woman, who complained of pain in the plantar aspect of the left foot. Magnetic resonance image (MRI) demonstrates three solitary nodules of varying sizes in the deep soft tissue of the plantar aspect of the foot that are homogeneously isointense to skeletal muscle on T1-weighted images and hyperintense on T2-weighted fat-suppressed images, especially the rim of the lesion. Subsequent pathological examination confirmed the diagnosis of PS. CONCLUSION: MRI characteristic plays an important role in detecting this rare lesion. A review of the literature on PS is also presented.

Identification of three small nucleolar RNAs (snoRNAs) as potential prognostic markers in diffuse large B-cell lymphoma.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a non-Hodgkin lymphoma with high mortality rates. Small nucleolar RNAs (snoRNAs) are tumor-specific biological markers, but there are few studies on the role of snoRNAs in DLBCL. MATERIALS AND METHODS: Survival-related snoRNAs were selected to construct a specific snoRNA-based signature via computational analyses (Cox regression and independent prognostic analyses) to predict the prognosis of DLBCL patients. To assist in clinical applications, a nomogram was built by combining the risk model and other independent prognostic factors. Pathway analysis, gene ontology analysis, transcription factor enrichment, protein-protein interactions, and single nucleotide variant analysis were used to explore the potential biological mechanisms of co-expressed genes. RESULTS: Twelve prognosis-correlated snoRNAs were selected from the DLBCL patient cohort of microarray profiles, and a three-snoRNA signature consisting of SNORD1A, SNORA60, and SNORA66 was constructed. DLBCL patients could be divided into high-risk and low-risk cohorts using the risk model, and the high-risk group and activated B cell-like (ABC) type DLBCL were linked with disappointing survival. In addition, SNORD1A co-expressed genes were inseparably linked to the biological functions of the ribosome and mitochondria. Potential transcriptional regulatory networks have also been identified. MYC and RPL10A were the most mutated SNORD1A co-expressed genes in DLBCL. CONCLUSION: Put together, our findings explored the potential biological effects of snoRNAs in DLBCL, and provided a new predictor for DLBCL prediction.

[Geochemical Characteristics of Cd in Different Parent Soils in Karst Area and Prediction of Cd Content in Maize].

The naturally high background value region of Cd derived from the weathering of carbonate has received wide attention. Due to the significant difference in soil physicochemical properties, soil Cd content, and bioavailability of different parent materials in the karst area, there are certain limitations in using the total soil Cd content to classify the environmental quality of cultivated land. In this study, surface soil and maize samples of eluvium and alluvial parent material in typical karst areas were collected systematically; the contents of maize Cd, soil Cd, pH, and oxides were analyzed, the Cd geochemical characteristics of different parent soils and the influencing factors of their bioavailability were revealed, and scientific and effective arable land use zoning suggestions based on the prediction model were suggested. The results showed that the physicochemical properties of different parent material soils in the karst area were obviously different. The alluvial parent material soil had low Cd content but high bioavailability, and the maize Cd exceeding rate was high. The maize Cd bioaccumulation factor was significantly negatively correlated with soil CaO, pH, Mn, and TC, and the correlation coefficients were -0.385, -0.620, -0.484, and -0.384, respectively. Compared with the multiple linear regression prediction model, using the random forest model to predict the maize Cd enrichment coefficient had higher accuracy and precision. Furthermore, a new scheme for the safe utilization of cultivated land at the plot scale based on soil Cd and predicted crop Cd content was proposed in this study, making full use of arable land resources to ensure crop safety.

Sintilimab combined with chidamide in the treatment of extranodal nature killer/T-cell lymphoma with secondary hemophagocytic lymphohistiocytosis: Two case reports and literature review.

RATIONALE: Extranodal nature killer/T-cell lymphoma (ENKTL) failing in asparaginase-containing treatments is fatal, it has a higher mortality rate when accompanied by secondary hemophagocytic lymphohistiocytosis (HLH). The study reported 2 ENKTL-related HLH patients. PATIENT CONCERNS: Patient 1 visited for nasal congestion and runny nose for 6 months then got a fever and serious myelosuppression after P-GEP (pegaspargase, gemcitabine, etoposide, and methylprednisolone) chemotherapy. Patient 2 complained of painless lymphadenectasis in the right neck for 4 months and experienced recurrent fever and poor performance status after 3 cycles of P-Gemox (pegaspargase, gemcitabine, and oxaliplatin) chemotherapy. DIAGNOSES: Patient 1 and patient 2 were diagnosed as ENKTL failing in asparaginase-based chemotherapy and involving secondary HLH. INTERVENTIONS: The dose of chidamide was 20 mg twice a week for 2 weeks and sintilimab was 200 mg once every 3 weeks. OUTCOMES: ENKTL was relieved and the HLH was resolved after the therapy of sintilimab and chidamide. The patients had achieved durable survival without immune-related adverse events. LESSONS: ENKTL-related HLH needs early diagnosis and treatment. The combined strategy of sintilimab plus chidamide help deal with HLH and solve ENKTL, it may be a useful treatment option for ENKTL-related HLH.

Chidamide combined with traditional chemotherapy for primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma: A case report.

BACKGROUND: Traditional chemotherapy has benefited many patients with non-Hodgkin's lymphoma, but results in a very poor response in patients with rare lymphomas or refractory lymphomas. Previous studies have shown that chidamide has potential anti-lymphoma activity and reverses lymphoma cell chemoresistance to increase the chemosensitivity of lymphoma cells to traditional chemotherapy. CASE SUMMARY: A 14-year-old boy was admitted to our hospital with a 5-d history of generalized erythema, papules, and blisters. Initially, the disease was refractory to potent anti-allergic and anti-infective treatment, and his condition progressively worsened. Skin biopsy revealed primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma. Considering that the disease is extremely rare in clinical practice, existing case reports have shown poor efficacy with traditional chemotherapy alone. We recommend chidamide combined with traditional chemotherapy for treatment. The regimen was as follows: Chidamide 30 mg/biw, cyclophosphamide 1100 mg/d1, pirarubicin 70 mg/d1, vincristine 2 mg/d1, dexamethasone 20 mg/d1-5, etoposide 100 mg/d1-5, in a 21 d cycle. The treatment effect was considerable, and complete remission was achieved after 4 cycles of treatment, after which the patient completed a total of 6 cycles of treatment. Subsequently, the patient regularly took chidamide 20 mg/biw as maintenance therapy for 1 year. To date, the patient has been disease-free for 3 years. CONCLUSION: This case suggests that the combination of chidamide and traditional chemotherapy is effective in primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma.

Unusual presentation of primary ovarian diffuse large B-cell lymphoma: a case report.

BACKGROUND: Primary ovarian lymphoma has been difficult to diagnose clinically and pathologically due to its rare incidence and non-specific clinical symptoms. CASE PRESENTATION: A 75-year-old female patient was reported in this study. The patient had a six-month history of changes in bowel habits, with occasional black feces and paroxysmal pain in the abdomen. The computed tomography scan of the pelvic cavity illustrated that rectal cancer and sigmoid colon adenocarcinoma invaded the lower part of the right-side ureter. The patient was once treated with excision of part of small intestine, fallopian tube and ovary, and uterus. The pathological examination of these excised tissues, combined with the immunohistochemistry, confirmed that the female patient suffered from primary ovarian diffuse large B-cell lymphoma (DLBCL), and the lymphoma had invaded the entire right-side ovary tissues, serous membranes on the posterior surface of the uterus, and the wall of small intestine. CONCLUSION: Few reports were available regarding the primary ovarian DLBCL. The initial symptom of the patient was the changes in bowel habits, which had not been reported beforehand. Hopefully, this case could helpfully render the early diagnosis possible, and increase clinical understanding of primary ovarian DLBCL, which would thereby reduce the chance of misdiagnosis.

[Exploring the Mechanism of Paclitaxel Inhibiting T-cell Lymphoma based on High-throughput Sequencing and Public Databases].

OBJECTIVE: To analyze gene expression profile of T cell lymphoma Jurkat cell line treated with paclitaxel by computational biology based on next generation sequencing and to explore the possible molecular mechanism of paclitaxel resistance to T cell lymphoma at gene level. METHODS: IC50 of paclitaxel on Jurkat cell line was determined by CCK-8 assay. Gene expression profile of Jurkat cells treated with paclitaxel was acquired by next generation sequencing technology. Gene microarray data related to human T cell lymphoma were screened from Gene Expression Omnibus (GEO) database (including 720 cases of T cell lymphoma and 153 cases of normal tissues). Combined with the sequencing data, differential expression genes (DEGs) were intersected and screened. DAVID database was used for enrichment analysis of GO function and KEGG pathway to determine and visualize functional entries of DEGs, and protein-protein interactions network of DEGs was drawn. The levels of gene expression were detected and verified by RT-qPCR. RESULTS: CCK-8 results showed that the proliferation of Jurkat cells was inhibited by paclitaxel depended on the concentration apparently. Treated by paclitaxel for 48 h, P<0.05 and |log2(FC)|≥1 were used as filter criteria on the results of RNA Sequencing (RNA-Seq) and GeoChip, 351 DEGs were found from Jurkat cells, including 323 up-regulated genes and 28 down-regulated genes. The GO functional annotation and KEGG pathway enrichment analysis showed that the role of paclitaxel was mainly concentrated in protein heterodimerization activity, nucleosome assembly and transcriptional dysregulation in cancer, etc. The results of RT-qPCR were consistent with those of the sequencing analysis, which verified the reliability of this sequencing. CONCLUSION: Paclitaxel can affect the proliferation and apoptosis of T-cell lymphoma by up-regulating JUN gene, orphan nuclear receptor NR4A family genes and histone family genes.

[Effects of mangiferin on cell cycle status and CDC2/Cyclin B1 expression of HL-60 cells].

OBJECTIVE: To study the effects of mangiferin on cell cycle status and CDC2/Cyclin B1 expression in HL-60 cells, and its molecular mechanism for treating leukemia. METHODS: The effect of Mangiferin on HL-60 cells proliferation was determined by MTT assay; The change of cell cycle status in HL-60 cells treated with mangiferin was performed by the flow cytometry; The expressions of CDC2 mRNA and Cyclin B1 mRNA were detected by semiquantitative RT-PCR. RESULTS: The growth inhibition effects of mangiferin in HL-60 cells were enhanced as the mangiferin concentration increased and exposure time prolonged; HL-60 cells in G2/M phase increased in a dose-dependent way 24 hours after mangiferin administration, indicating G2/M phase blockage; the expressions of CDC2 mRNA and Cyclin B1 mRNA enhanced in a dose-dependent way and came to the peak at 80 micromol/L mangiferin. CONCLUSION: Mangiferin can inhibit the proliferation of HL-60, block the cell cycle progression in G2/M phase, and it can significantly increase the expressions of CDC2 mRNA and Cyclin B1 mRNA of HL-60 cells. G2/M phase blockage may be one of its molecular mechanism for treating leukemia.

[Effect of Mangiferin on Proliferation of FLT3-ITD Mutation Positive Acute Myeloid Leukemia Cell MV4-11 and Its Mechanism].

OBJECTIVE: To investigate the effects of mangiferin on proliferation, apoptosis and cycle of FLT3-ITD mutation-positive acute myeloid leukemia cells and its mechanism. METHODS: The effects of different concentration of mangiferin on proliferation of MV4-11 cells were detected by CCK8 method. Apoptosis, cell cycle and FLT3 transmembrane protein expression were detected by flow cytometry. FLT3 mRNA expression was detected by real-time fluorescent quantitative polymerase chain reaction (PCR) . RESULTS: Mangiferin obviously inhibited MV4-11 proliferation in a concentration and time dependent manner (48 h，r=0.922；72 h，r=0.959；96 h，r=0.973). The ratio of G0/G1 phase in cell cycle increased with the enhancement of concentration of mangiferin in MV4-11 cells for 48 h, and the ratio of S phase decreased with enhasment of concentration. The increase of apoptosis was more obvious. The expression of FLT3 transmembrane protein significantly decreased after the actior of IC50 concentration of mangiferin in MV4-11 cells for 48 h. The results of qRT-PCR showed that the expression of FLT3 mRNA significantly decreased after treatment of MN4-11 cells with mangiferin (P＜0.05). CONCLUSION: Mangiferin inhibits MV4-11 cell proliferation, arrests cell cycle progression and promotes apoptosis, which may be related with the inhibition of FLT3 activity by mangiferin and the subsequent signaling pathways involved in apoptosis and proliferation of cells.

Comprehensive clinical implications of homeobox A10 in 3,199 cases of non-small cell lung cancer tissue samples combining qRT-PCR, RNA sequencing and microarray data.

In the current study, we proposed to explore the potential role and related signaling pathways of Homobox A10 (HOXA10) in non-small cell lung cancer (NSCLC). HOXA10 levels in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) were detected by qRT-PCR and the expression of HOXA10 was significantly up-regulated in the NSCLC tissue of all 55 pairs (P = 0.037). Overexpression of HOXA10 was closely correlated with the clinical stage of LUSC (P = 0.011). HOXA10 expression in RNA sequencing data based on 1, 077 cases exhibited concordant significant up-regulation in NSCLC, LUAD and LUSC (P < 0.001). In NSCLC, HOXA10 expression was closely correlated to patient T stage (P = 0.006). In LUAD, HOXA10 expression was compactly correlated to patient N stage (P = 0.02). Some of the microarrays from Gene Expression Omnibus (GEO) and ArrayExpress showed consistent over-expression of HOXA10 levels in NSCLCs. More importantly, the combined SMD value was 0.052 (95% CI: 0.29-0.75, P < 0.001) generated by meta-analysis from 47 datasets based on 4, 616 cases of NSCLC. The area under the curve (AUC) of SROC supported the over-expression of HOXA10 in NSCLC as being 0.88 (95% CI: 0.81-0.93), with sensitivity and specificity of 0.88 (95% CI: 0.81-0.93) and 0.56 (95% CI: 0.44-0.66), respectively. In addition, 111 co-expressed genes were collected from cBioPortal and enriched in "cell cycle", "cell adhesion molecules", "p53 signaling", and "adherens junction". Interestingly, an up-regulation trend of HOXA10 protein expression was also observed in NSCLC through tissue chips and immunohistochemistry. In conclusion, the overexpression of HOXA10 may play a pivotal role in the tumorigenesis of NSCLC, and this effect is observed more obviously in LUSC than in LUAD.

Expression and clinical significance of neuropilin-1 in Epstein-Barr virus-associated lymphomas.

BACKGROUND: The expression of neuropilin-1 (NRP-1) in Epstein-Barr virus (EBV)-associated lymphomas and its relationships with clinicopathological parameters was investigated. METHODS: The researchers compared 111 cases of patients with lymphoma to 20 cases of reactive lymphoid hyperplasia. In situ hybridization was applied to observe the expression of EBV-encoded RNA (EBER) in lymphomas, and immunohistochemistry was used to detect the NRP-1 expression in lymphoma tissues and lymph node tissues with reactive hyperplasia. RESULTS: In these 111 cases, the EBER of 62 cases (55.9%) appeared positive. NRP-1 was relatively highly expressed in lymphomas (P= 0.019). Further, NRP-1 showed higher expression in lymphomas with positive EBER than in negative ones. A comprehensive analysis revealed that NRP-1 was differently expressed in NK/T-cell lymphoma, Hodgkin's lymphoma, diffuse large B-cell lymphoma, and anaplastic large cell lymphoma (P= 0.027). Moreover, highly expressed NRP-1 was found to be a useful independent prognostic factor in assessing overall survival and progression-free survival rates in cases of non-Hodgkin's lymphoma (NHL). CONCLUSIONS: NRP-1 exhibited higher expression in lymphomas, and it was positively expressed in EBV-positive lymphomas. Moreover, highly expressed NRP-1 can be used as an undesirable independent prognostic factor in NHL.

Prognostic alternative splicing signatures and underlying regulatory network in esophageal carcinoma.

Alternative splicing (AS) has been widely reported to play an important role in cancers, including esophageal carcinoma (ESCA). However, no study has comprehensively investigated the clinical use of combination of prognostic AS events and clinicopathological parameters. Therefore, we collected 165 ESCA patients including 83 esophageal adenocarcinoma (EAC) and 82 esophageal squamous cell carcinoma (ESCC) patients from The Cancer Genome Atlas to explore the survival rate associated with seven types of AS events. Prognostic predictors for the clinical outcomes of ESCA patients were built. Predictive prognosis models of the alternative acceptor site in ESCA (area under the curve [AUC] = 0.83), alternative donor site in EAC (AUC = 0.99), and alternative terminator site in ESCC (AUC = 0.974) showed the best predictive efficacy. A novel combined prognostic model of AS events and clinicopathological parameters in ESCA was also constructed. Combined prognostic models of ESCA all showed better predictive efficacy than independent AS models or clinicopathological parameters model. Through constructing splicing regulatory network, the expression of AS factor was found to be negatively correlated with the most favorable AS events. Moreover, gene amplification, mutation, and copy number variation of AS genes were commonly observed, which may indicate the molecular mechanism of how the AS events influence survival. Conclusively, the constructed prognostic models based on AS events, especially the combined prognostic models of AS signatures and clinicopathological parameters could be used to predict the outcome of ESCA patients. Moreover, the splicing regulatory network and genomic alteration in ESCA could be used for illuminating the potential molecular mechanism.

Expression significance and potential mechanism of hypoxia-inducible factor 1 alpha in patients with myelodysplastic syndromes.

OBJECTIVE: To investigate the expression level and potential mechanism of hypoxia-inducible factor 1 alpha (HIF-1α) in patients with myelodysplastic syndromes (MDS). METHODS: Immunohistochemistry (IHC) techniques were used to examine the protein expression of HIF-1α in paraffin-embedded myeloid tissues from 82 patients with MDS and 33 controls (patients with lymphoma that is not invading myeloid tissues). In addition, the associations between the protein expression of HIF-1α and clinical parameters were examined. To further investigate the significance of HIF-1α expression in MDS patients, the researchers not only extracted the data about HIF-1α expression from MDS-related microarrays but also analyzed the correlation between the level of HIF-1α expression and MDS. The microRNA (miRNA) targeting HIF-1α was predicted and verified with a dual luciferase experiment. RESULTS: Immunohistochemistry revealed that the positive expression rate of HIF-1α in the bone marrow of patients with MDS was 90.24%. This rate was remarkably higher than that of the controls (72.73%) and was statistically significant (P < .05), which indicated that HIF-1α was upregulated in the myeloid tissues of MDS patients. For the GSE2779, GSE18366, GSE41130, and GSE61853 microarrays, the average expression of HIF-1α in MDS patients was higher than in the controls. Particularly for the GSE18366 microarray, HIF-1α expression was considerably higher in MDS patients than in the controls (P < .05). It was predicted that miR-93-5p had a site for binding with HIF-1α, and a dual luciferase experiment confirmed that miR-93-5p could bind with HIF-1α. CONCLUSION: The upregulated expression of HIF-1α was examined in the myeloid tissues of MDS patients. The presence of HIF-1α (+) suggested an unsatisfactory prognosis for patients, which could assist in the diagnosis of MDS. In addition, miR-93-5p could bind to HIF-1α by targeting, showing its potential to be the target of HIF-1α in MDS.

Clinical Significance of microRNA-196b-5p in Hepatocellular Carcinoma and its Potential Molecular Mechanism.

Objective: To enquire into the clinical significance and potential molecular mechanism of microRNA (miRNA)-196b-5p in hepatocellular carcinoma (HCC). Methods: Quantitative reverse transcription and polymerase chain reaction (qRT-PCR) were utilized to examine miR-196b-5p expression level in 67 HCC paraffin embedded tissues and corresponding adjacent tissues. Correlations of miR-196b-5p expression level with clinicopathological characteristics were analyzed in our study. The expression level and clinical significance of miR-196b-5p in HCC were also evaluated in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. We made predictions of the target genes of miR-196b-5p by twelve online software and then selected genes predicted by at least 5 software. Subsequently, in order to obtain the potential target genes of miR-196b-5p, we overlapped the predicted target genes and down-regulated mRNAs in HCC based on TCGA database. Then, we performed the Gene Ontology (GO) and the Disease Ontology (DO) functional annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and Protein-Protein Interaction (PPI) network construction of those miR-196b-5p potential target genes. Results: Higher expression level of miR-196b-5p was seen in HCC tissues than in the corresponding adjacent tissues based on qRT-PCR (P = 0.0007). The expression level of miR-196b-5p was linked with tumor size (P = 0.03), tumor node (P = 0.024), vascular invasion (P = 0.029) and capsular invasion (P = 0.026) in HCC patients. Comprehensive meta-analysis of miR-196b-5p expression based on TCGA, GEO and qRT-PCR verified that higher expression level of miR-196b-5p was observed in HCC tissues than in normal control liver tissues (SMD = 0.56, 95%CI: 0.39-0.72, P heterogeneity = 0.275, I2 = 18.3%). GO annotation revealed that the top terms in biological process, cellular component and molecular function were single-organism catabolic process, neuronal cell body and transmembrane receptor protein kinase activity, respectively. The most relevant disease in DO annotation was arteriosclerosis. The tryptophan metabolism pathway ranked first in KEGG pathway enrichment analysis. The PPI network showed that IGF1, FOXO1, AR and FOS were mostly likely to become the core genes of miR-196b-5p potential target genes, which however required further experiments for validation. Conclusion: The miR-196b-5p was observed to show higher expression in HCC tissues than in normal control liver tissues. Moreover, the miR-196b-5p expression level had correlations with the clinicopathological parameters such as vascular invasion of HCC, but the molecular mechanisms of miR-196b-5p in HCC still need further elucidation and verification.

miR­146a­5p targets TCSF and influences cell growth and apoptosis to repress NSCLC progression.

Several studies have indicated that microRNAs (miRs) mediate multiple pathways associated with tumorigenesis and progression. Our preliminary study experimentally verified that miR­146a­5p has a role in the biological behavior of non­small cell lung cancer (NSCLC) cells. To perform further investigation of miR­146a­5p, the present study evaluated miR­146a­5p by targeting its downstream gene tumor collagenase stimulatory factor (TCSF) to influence cell viability, proliferation and apoptosis in NSCLC. Online sequence prediction, a thorough search of the open source database The Cancer Genome Atlas (TCGA), immunohistochemistry (IHC) of TCSF in clinical lung cancer tissues, and a dual­luciferase assay, as well as assays to test viability, proliferation and apoptosis in vitro, were conducted to explain the targeted regulation association between miR­146a­5p and TCSF in NSCLC. The miRanda and TargetScanHuman database revealed that TCSF and miR­146a­5p had target binding sites. A luciferase reporter assay demonstrated that miR­146a­5p and TCSF did have complementary sequences (P<0.05). From the TCGA database, TCSF was highly expressed in lung adenocarcinoma and lung squamous cell carcinoma tissues when compared with normal lung tissues (P<0.05). Furthermore, the protein level of TCSF in cancerous lung tissues was determined by IHC, and it was concluded that TCSF protein was also upregulated in NSCLC tissues (P<0.001). A significant difference was identified following in vitro experiments for the NSCLC cell line A549, which revealed that miR­146a­5p and TCSF regulated cell viability, proliferation and apoptosis. In conclusion, the present study verified the target action association between TCSF and miR­146a­5p with high throughput data analysis and experimental results in NSCLC.