RESUMO
Searching for the novel tumour biomarkers is pressing for gastric cancer diagnostication and prognostication. The serum specimens from patients diagnosed with locally advanced gastric carcinoma before operation and 4 week after surgery were collected, respectively, and serum proteome profiling was conducted by liquid chromatography-mass spectrometry (MS)/MS. Fifty-five proteins were identified to be up-regulated and 16 proteins were down-regulated, and these differentially expressed proteins participated in various biological processes. Serum levels of SOX3, one of down-regulated proteins, in stomach cancer patients were higher than in healthy controls. SOX3 levels in cancer tissues were remarkably related to tumour differentiation, lymph node metastasis, primary tumour invasion and pTNM (pathological TNM) stage. Analysis with The Cancer Genome Atlas database indicated that SOX3 level and pTNM stage were the independent risk factors for the patient survival and that the overall survival was negatively associated with the SOX3 levels. Loss-of-function showed that SOX3 promoted gastric cancer cell invasion and migration in vitro and in vivo. SOX3 silence inhibits the expression of MMP9, and SOX3 is responsible for MMP9 expression transcriptionally. Our study highlights the potentiality of the paired pre- and post-operation serum proteome signatures for the detection of biomarkers and reveals that SOX3 may serve as a candidate prognosis marker for gastric cancer.
Assuntos
Biomarcadores Tumorais/sangue , Proteoma/metabolismo , Proteômica , Fatores de Transcrição SOXB1/sangue , Neoplasias Gástricas/sangue , Movimento Celular , Regulação para Baixo , Feminino , Humanos , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Hand-sewn anastomosis and stapled anastomosis are the 2 main types of gastrojejunal anastomotic methods in pancreaticoduodenectomy. There is ongoing debate regarding the most effective anastomotic method for reducing delayed gastric emptying after pancreaticoduodenectomy. This study aims to identify factors that influence delayed gastric emptying after pancreaticoduodenectomy and assess the impact of different anastomotic methods on delayed gastric emptying. METHODS: The study included 1,077 patients who had undergone either hand-sewn anastomosis (n = 734) or stapled anastomosis (n = 343) during pancreaticoduodenectomy between December 2016 and November 2021 at our department. We retrospectively analyzed the clinical data, and a 1:1 propensity score matching was performed to balance confounding variables. RESULTS: After propensity score matching, 320 patients were included in each group. Compared with the stapled anastomosis group, the hand-sewn anastomosis group had a significantly lower incidence of delayed gastric emptying (28 [8.8%] vs 55 [17.2%], P = .001) and upper gastrointestinal tract bleeding (6 [1.9%] vs 17 [5.3%], P = .02). Additionally, the hand-sewn anastomosis group had a significantly reduced postoperative length of stay and lower hospitalization expenses. However, the hand-sewn anastomosis group had a significantly longer operative time, which was consistent with the analysis before propensity score matching. Logistic regression analysis showed that stapled anastomosis, intra-abdominal infection, and clinically relevant postoperative pancreatic fistula were independent prognostic factors for delayed gastric emptying. CONCLUSION: Hand-sewn anastomosis was associated with a lower incidence rate of clinically relevant delayed gastric emptying after pancreaticoduodenectomy. Stapled anastomosis, intra-abdominal infection, and clinically relevant postoperative pancreatic fistula could increase the incidence of postoperative clinically relevant delayed gastric emptying. Hand-sewn anastomosis should be considered by surgeons to reduce the occurrence of postoperative delayed gastric emptying and improve patient outcomes.
Assuntos
Gastroparesia , Infecções Intra-Abdominais , Humanos , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/métodos , Estudos Retrospectivos , Gastroparesia/epidemiologia , Gastroparesia/etiologia , Gastroparesia/prevenção & controle , Fístula Pancreática/epidemiologia , Fístula Pancreática/etiologia , Fístula Pancreática/prevenção & controle , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Infecções Intra-Abdominais/complicações , Esvaziamento Gástrico , Resultado do TratamentoRESUMO
BACKGROUND: The dysregulated long non-coding RNA (lncRNA) small nucleolar RNA host genes (SNHGs) have been demonstrated to be involved in gastric carcinogenesis and progression; however, the role of SNHG17 in gastric carcinoma remains to be investigated. We aimed to ascertain the expression of SNHG17 in gastric carcinoma tissues and cell lines, and to investigate its mechanistic role in this malignancy. METHODS: The expression levels of SNHG17, P15, P16, P18, P19 and cyclin dependent kinases-4 (CDK4) were determined by real-time quantitative polymerase chain reaction (RT-qPCR) and/or western blotting in human gastric cancer tissues and cell lines. Correlations between SNHG17 levels and clinicopathological features were evaluated. siRNAs were used to silence SNHG17 in cell lines, and then Cell Counting Kit-8, colony formation, and transwell migration assays were used to assess proliferation, clonogenic potential, and migration, respectively. Flow cytometry was used to analyze cell cycle distributions and apoptosis. In vivo tumorigenicity was evaluated using xenografts in nude mice. RESULTS: Analysis of The Cancer Genome Atlas (TCGA) database revealed that SNHG17 expression was remarkably higher in gastric carcinoma tissues than normal stomach mucosae (P=4.85×10-10). We confirmed that SNHG17 was overexpressed in gastric cancer tissues (P<0.0001) and cell lines (P<0.01) compared with corresponding noncancerous tissues and gastric epithelial cell line, respectively. Furthermore, SNHG17 levels in tumor tissues were associated with lymph node metastasis (P=0.0006), pTNM stage (P=0.0061), and lymphovascular invasion (P=0.0005), but were not associated with overall survival (OS) (P=0.888). Loss-of-function studies indicated that SNHG17 promoted gastric carcinoma cell proliferation in vitro and in vivo (P<0.01), and that SNHG17 enhanced gastric cancer cell migration (P<0.01). Mechanistically, we found that SNHG17 inhibited P15 and P16, and enhanced CDK4 expression, resulting in a G0/G1 cell cycle arrest, and that SNHG17 inhibited cell apoptosis. CONCLUSIONS: These preliminary findings highlight the role of SNHG17 in gastric cancer, and suggest that it may be a novel indicator and/or a potential therapeutic target for diagnosing and/or treating gastric cancer.