RESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent and aggressive malignancies worldwide. Studies seeking to advance the overall understanding of lncRNA profiling in HCC remain rare. METHODS: The transcriptomic profiling of 12 HCC tissues and paired adjacent normal tissues was determined using high-throughput RNA sequencing. Fifty differentially expressed mRNAs (DEGs) and lncRNAs (DELs) were validated in 21 paired HCC tissues via quantitative real-time PCR. The correlation between the expression of DELs and various clinicopathological characteristics was analyzed using Student's t-test or linear regression. Co-expression networks between DEGs and DELs were constructed through Pearson correlation co-efficient and enrichment analysis. Validation of DELs' functions including proliferation and migration was performed via loss-of-function RNAi assays. RESULTS: In this study, we identified 439 DEGs and 214 DELs, respectively, in HCC. Furthermore, we revealed that multiple DELs, including NONHSAT003823, NONHSAT056213, NONHSAT015386 and especially NONHSAT122051, were remarkably correlated with tumor cell differentiation, portal vein tumor thrombosis, and serum or tissue alpha fetoprotein levels. In addition, the co-expression network analysis between DEGs and DELs showed that DELs were involved with metabolic, cell cycle, chemical carcinogenesis, and complement and coagulation cascade-related pathways. The silencing of the endogenous level of NONHSAT122051 or NONHSAT003826 could significantly attenuate the mobility of both SK-HEP-1 and SMMC-7721 HCC cells. CONCLUSION: These findings not only add knowledge to the understanding of genome-wide transcriptional evaluation of HCC but also provide promising targets for the future diagnosis and treatment of HCC.
Assuntos
Carcinoma Hepatocelular/metabolismo , RNA Longo não Codificante/metabolismo , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Movimento Celular/fisiologia , Regulação Neoplásica da Expressão Gênica/genética , Humanos , RNA Longo não Codificante/genética , Reação em Cadeia da Polimerase em Tempo RealRESUMO
OBJECTIVE: To evaluate the value of transvaginal ultrasound parameters before and after cerclage in twins in predicting spontaneous preterm birth (sPTB) before 28+0 weeks. METHODS: We retrospectively studied the medical records of twin-pregnant women who underwent ultrasound-indicated cerclage between January 2016 and February 2022 at our hospital. Recorded transvaginal ultrasound images before and after cerclage were reassessed for cervical length (CL), uterocervical angle (UCA), funneling, and sludge. Multivariate logistic and Cox regression analyses were performed to identify the independent risk factors associated with sPTB before 28 weeks. RESULTS: A total of 69 women were included. Among them, 17 women (24.64%) delivered before 28 weeks of age. Regression analysis revealed a significant association of post-cerclage CL, UCA, white blood cell (WBC) count, and gestational age (GA) at cerclage with sPTB before 28 weeks. The area under the curve of these predictors was 0.938 (95% confidence interval, 0.882-0.994; p < .001), with a sensitivity of 88.2%, specificity of 92.3%, positive predictive value of 78.9%, and negative predictive value of 96.0%. Cox analysis showed that post-cerclage UCA was an independent risk factor affecting the cerclage-to-delivery interval (hazard ratios, 1.026; 95% confidence interval (CI), 1.004-1.048; p = .019). CONCLUSIONS: The combination of post-cerclage CL, UCA, WBC count, and GA at cerclage showed good performance in predicting sPTB at <28 weeks in twin pregnancy. Post-cerclage UCA is also associated with pregnancy latency. We found that post-cerclage cervical ultrasound may be useful to predict preterm birth before 28 weeks in twins who undergo ultrasound-indicated cerclage.
Assuntos
Cerclagem Cervical , Colo do Útero , Nascimento Prematuro , Ultrassonografia Pré-Natal , Feminino , Humanos , Recém-Nascido , Gravidez , Medida do Comprimento Cervical , Colo do Útero/diagnóstico por imagem , Colo do Útero/cirurgia , Gravidez de Gêmeos , Nascimento Prematuro/diagnóstico por imagem , Nascimento Prematuro/etiologia , Nascimento Prematuro/prevenção & controle , Estudos Retrospectivos , Ultrassonografia Pré-Natal/métodosRESUMO
BACKGROUND: In recent years, long non-coding RNAs (lncRNAs) have been shown to play a critical regulatory role in cancer biology. However, the contribution of lncRNAs to papillary thyroid cancer (PTC) remains largely unknown. METHODS: RNA sequencing and quantitative reverse transcription polymerase chain reaction were used to detect and verify changes to the transcriptome profile in 12 PTC tissues compared to paired normal adjacent tissues. The statistical correlation between differentially expressed lncRNAs and clinicopathologic characteristics was analyzed, and potential lncRNA functions were predicted by examining annotations for the co-expressed mRNAs. Furthermore, the specific subgroup patterns of the PTC transcriptome remodeled by BRAF mutations were also analyzed. RESULTS: A total of 188 lncRNAs and 505 mRNAs were differentially expressed in 50% or more of the PTC tissues (fold change >2; p < 0.05) as assessed by RNA-sequencing compared with paired normal adjacent tissues. Forty-seven lncRNAs and 39 mRNAs were verified in 31 pairs of PTC specimens using quantitative reverse transcription polymerase chain reaction, and the results were consistent with the RNA sequencing data. The lncRNAs NONHSAT076747 and NONHSAT122730 were associated with lymph node metastasis, and NONHSAG051968 expression was negatively correlated with tumor size. A co-expression network between differentially expressed lncRNAs and protein-coding RNAs was constructed and analyzed, and functional analysis suggested that the differentially expressed genes mainly participate in ECM-receptor interactions and the focal adhesion pathway. Furthermore, a specific PTC transcriptome subtype pattern stratified by BRAF mutation was also uncovered. The p53 signaling pathway was the most highly enriched pathway among the BRAF mutation-related genes. CONCLUSIONS: This study reveals specific changes to the lncRNA profile associated with PTC, and provides new insight into its pathogenesis. The PTC-associated lncRNAs NONHSAG051968, NONHSAT076747, and NONHSAT122730 might be potential diagnostic and therapeutic targets for PTC patients, and lncRNAs with subtype-specific expression stratified by BRAF mutation might be significant in individual molecular subtypes.
Assuntos
Carcinoma Papilar/genética , Regulação Neoplásica da Expressão Gênica , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , RNA Longo não Codificante/genética , Neoplasias da Glândula Tireoide/genética , Adulto , Carcinoma Papilar/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência de RNA , Neoplasias da Glândula Tireoide/patologiaRESUMO
Hepatoid adenocarcinoma (HAC), an extrahepatic tumor, has notable morphological similarities to hepatocellular carcinoma, which has been reported in gastrointestinal tract organs, including the rectum, gallbladder, lung, ovary and urinary bladder. HAC of the stomach (GHAC) is a rare variant of gastric cancer, characterized by aggressive behavior and extremely poor prognosis. Correct diagnosis depends on clinicopathological and immunohistochemical studies. In the present study, we reported nine cases of GHAC who were treated in the First Affiliated Hospital of Zhejiang University, China, from January 2009 to December 2013. All patients underwent radical gastrectomy; among them, one patient had stage I, one had stage II and seven had stage III. Elevated serum α-fetoprotein was observed in eight cases. Until now, only one patient has succumbed, four patients have liver metastases, one has lung metastasis and four remain disease-free. Relatively longer survival requires accurate diagnosis at an earlier stage and active multimodality treatment, including radical gastrectomy and adjuvant chemotherapy.