RESUMO
OBJECTIVE: This study aims to comprehensively analyze alternative splicing (AS) features in colorectal cancer (CRC) using integrative multi-omics and to elucidate their relationship with the CRC immune microenvironment. METHODS: Transcriptomic data, clinical information, and Percent Spliced In (PSI) values of AS events for CRC patients were obtained from The Cancer Genome Atlas (TCGA) and TCGA SpliceSeq databases. Differentially expressed AS events were identified. Univariate Cox analysis was used to pinpoint prognosis-related AS events. A prognostic risk model was developed and validated using multivariate Cox analysis, patient survival analysis, and the area under the receiver operating characteristic (ROC) curve (AUC). Gene Set Enrichment Analysis (GSEA), immune infiltration, immunotherapy, chemotherapy sensitivity analyses, and regulatory relationships between AS events and splicing factors (SFs) were conducted. Single-cell sequencing was used to study the distribution of key factors. siRNA and overexpression vectors were utilized to silence/overexpress BCAS1 in CRC cells and evaluate their effects on cell growth, migration, and invasion. Furthermore, the interaction between BCAS1 and ANO7 pre-mRNA was investigated using RIP-PCR. RESULTS: 82 prognosis-related AS events were identified in CRC patients. A 15-AS prognostic model was constructed, which correlated with immune cell infiltration and showed differences in immunotherapy and chemotherapy sensitivity. BCAS1 was identified as a potential regulator of the ANO7|58341|AT splicing event in CRC. Single-cell sequencing analysis revealed the distribution of BCAS1 and ANO7 in cancer stem cells. In vitro experiments demonstrated that overexpression of BCAS1 and silencing of ANO7 inhibit the proliferation, migration, and invasion of CRC cells. Moreover, BCAS1 suppresses the progression of CRC by modulating ANO7 alternative splicing. CONCLUSION: This study provides new insights into the role of alternative splicing in colorectal cancer, particularly the potential regulatory action of BCAS1 on the ANO7|58341|AT splicing event. It also identifies the impact of alternative splicing on the tumor microenvironment and potential implications for immunotherapy, highlighting its relevance for the in-depth study and treatment of CRC.
Assuntos
Processamento Alternativo , Neoplasias Colorretais , Microambiente Tumoral , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/terapia , Prognóstico , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Imunoterapia/métodos , Feminino , Masculino , Movimento Celular/genética , Proliferação de Células/genética , Linfócitos do Interstício Tumoral/imunologia , Biomarcadores Tumorais/genéticaRESUMO
OBJECTIVE: To study the GI symptoms in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. DESIGN: We analysed epidemiological, demographic, clinical and laboratory data of 95 cases with SARS-CoV-2 caused coronavirus disease 2019. Real-time reverse transcriptase PCR was used to detect the presence of SARS-CoV-2 in faeces and GI tissues. RESULTS: Among the 95 patients, 58 cases exhibited GI symptoms of which 11 (11.6%) occurred on admission and 47 (49.5%) developed during hospitalisation. Diarrhoea (24.2%), anorexia (17.9%) and nausea (17.9%) were the main symptoms with five (5.3%), five (5.3%) and three (3.2%) cases occurred on the illness onset, respectively. A substantial proportion of patients developed diarrhoea during hospitalisation, potentially aggravated by various drugs including antibiotics. Faecal samples of 65 hospitalised patients were tested for the presence of SARS-CoV-2, including 42 with and 23 without GI symptoms, of which 22 (52.4%) and 9 (39.1%) were positive, respectively. Six patients with GI symptoms were subjected to endoscopy, revealing oesophageal bleeding with erosions and ulcers in one severe patient. SARS-CoV-2 RNA was detected in oesophagus, stomach, duodenum and rectum specimens for both two severe patients. In contrast, only duodenum was positive in one of the four non-severe patients. CONCLUSIONS: GI tract may be a potential transmission route and target organ of SARS-CoV-2.
Assuntos
Betacoronavirus , Infecções por Coronavirus , Trato Gastrointestinal , Pandemias , Pneumonia Viral , Adulto , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Feminino , Trato Gastrointestinal/fisiopatologia , Trato Gastrointestinal/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , SARS-CoV-2RESUMO
AIMS: To evaluate the effectiveness and safety of endoscopic resection for gastric gastrointestinal stromal tumors (GISTs). MATERIAL AND METHODS: The effectiveness and safety of endoscopic resection were mainly assessed by complete resection rate, postoperative adverse event rate, and recurrence rate. Moreover, a comparison of endoscopic with laparoscopic resection for gastric GISTs was made through weighted mean difference by STATA 12.0 with regard to operation time, blood loss, and length of stay after including patients who underwent endoscopic or laparoscopic resection for gastric GISTs in the comparative studies. RESULTS: Eleven studies investigating endoscopic resection for GISTs were included. For stromal tumors <2 cm in average diameters the pooled rates of complete resection, postoperative adverse events and recurrence were 0.97, 0.08, and 0.03, respectively. Only five retrospective studies directly compared endoscopic with laparoscopic resection for gastric GISTs with average diameters from 1.1 cm to 3.8 cm, and endoscopic resection had a shorter operation time than laparoscopic resection, but there were no significant differences in intraoperative blood loss, length of stay, postoperative complications, and postoperative recurrence rates between the two approaches. CONCLUSIONS: Endoscopic resection is predominantly tried for gastric GISTs of relatively small size. It seems effective and safe for gastric GISTs <2 cm in average diameter, with relatively short operation times.