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1.
Carcinogenesis ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829328

RESUMO

Cancer cells exhibit heterogenous metastatic potential, and high metastatic subclones can enhance metastatic potential of low metastatic subclones by transmitting some factors. Exosomal miRNAs play a pivotal role in the crosstalk of heterogenous metastatic subclones. This study discovered that miR-20a-3p was upregulated in colorectal adenocarcinoma (CRA), correlated with metastasis, and potentially served as a prognostic indicator for CRA. miR-20a-3p could promote the proliferation, migration and invasion of CRA cells. Interestingly, high metastatic CRA cells could promote malignant phenotypes of low metastatic CRA cells by transmitting exosomal miR-20a-3p. Mechanically, miR-20a-3p could inhibit NF1, thereby activate the RAS-mediated mitogen-activated protein kinases (MAPK) signaling pathway to drive the metastasis of CRA. In summary, our study provided the evidence that colorectal cancer cells with high metastatic potential drive metastasis by transmitting exosomal miR-20a-3p through modulating NF1/MAPK pathway.

2.
Front Oncol ; 14: 1352660, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38511138

RESUMO

Background: The treatment strategy for stage II rectal mucinous adenocarcinoma (RMA) recommends neoadjuvant chemoradiotherapy (NCR) followed by total mesorectal excision (TME). However, the necessity of adjuvant chemotherapy (AC) remains controversial. Materials and methods: Chi-square test was used to assess the relationship between pathological classification, AC and clinicopathological characteristics. Kaplan-Meier (KM) curves and the log-rank test were utilized to analyze differences in overall survival (OS) and cancer-specific survival (CSS) among different groups. Cox regression identified prognostic factors. Nomogram was established utilizing the independent prognostic factors. X-tile divided patients into three risk subgroups. Results: Compared to RMA, rectal adenocarcinoma (RA) demonstrates longer OS and CSS in all and non-AC stage II patients, with no difference in OS and CSS for AC stage II patients. Propensity score matching analyses yielded similar results. Stratified analysis found that AC both improve OS of RA and RMA patients. Age, gender, pathologic T stage, regional nodes examined, and tumor size were identified as independent prognostic factors for RMA patients without AC. A nomogram was constructed to generate risk scores and categorize RMA patients into three subgroups based on these scores. KM curves revealed AC benefits for moderate and high-risk groups but not for the low-risk group. The external validation cohort yielded similar results. Conclusions: In summary, our study suggests that, compared to stage II RA patients, stage II RMA patients benefit more from AC after NCR. AC is recommended for moderate and high-risk stage II RMA patients after NCR, whereas low-risk patients do not require AC.

3.
J Robot Surg ; 17(6): 3025-3033, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37950110

RESUMO

Robotic surgery is widely used in gastrointestinal surgery. While the application of robotic surgery for colon cancer patients with previous abdominal surgery (PAS) remains controversial for the fear of intra-abdominal adhesions. This study was aimed to evaluate the safety and feasibility of robotic colectomy for patients with PAS. The medical records of colon cancer patients who underwent robotic surgery at our hospital from June 2015 to August 2020 were extracted and analyzed. Propensity score-matching (PSM) analysis was implemented to minimize selection bias. We compared perioperative outcomes and postoperative complications between the patients with PAS or with no PAS (NPAS). A total of 79 patients (PAS group) and 348 patients (NPAS group) were included in our study. After PSM, 79 patients of PAS group and 79 patients of NPAS group were selected for further analysis. We did not find statistical difference in operative time, estimated blood loss, lymph nodes retrieved, length of hospital stay and hospital costs between the two groups. No difference was noted in the incidence of postoperative complications, conversion to open surgery and mortality between the two groups. According to the results of multivariate analysis, PAS was not identified as risk factor for postoperative complications. Left hemicolectomy and perioperative transfusion were associated with postoperative complications. PAS did not negatively affect the outcomes of robotic colectomy. After individually preoperative assessment, robotic surgery could be performed feasibly and safely for colon cancer patients with PAS.


Assuntos
Neoplasias do Colo , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Laparoscopia/métodos , Pontuação de Propensão , Estudos de Viabilidade , Resultado do Tratamento , Estudos Retrospectivos , Neoplasias do Colo/cirurgia , Complicações Pós-Operatórias/etiologia , Colectomia/efeitos adversos , Colectomia/métodos
4.
J Gastrointest Surg ; 27(12): 2857-2866, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37989932

RESUMO

BACKGROUND: Although rectal mucinous adenocarcinoma (RMC) is less sensitive to radiotherapy, adjuvant radiotherapy is still recommended for RMC patients. This study aimed to explore whether adjuvant radiotherapy is necessary for stage III RMC. METHODS: Data of patients with stage III RMC were obtained from the National Cancer Institute's SEER database (2004-2015). The survival rates were calculated by Kaplan-Meier method and compared by log-rank test. Univariate and multivariate Cox regression analyses were used to assess the impact of clinicopathological parameters on overall survival (OS) and cancer-specific survival (CSS). RESULTS: RMC has a worse T and N stage at diagnosis than rectal adenomatous carcinoma (RAC) (all p < 0.001). Multivariate Cox regression analyses revealed that histopathological type MC was an independent poor prognostic factor for OS (HR 1.27; 95%CI 1.14-1.41; p < 0.001) and CSS (HR 1.34; 95%CI 1.18-1.51; p < 0.001). Subgroup analysis based on different treatment regimens showed no significant difference between chemotherapy group and chemotherapy plus radiotherapy group. After the propensity score matching, no significant difference was also found in OS and CSS between chemotherapy group and chemotherapy plus radiotherapy group. CONCLUSIONS: RMC is an independent poor prognostic factor for OS and CSS. Adjuvant radiotherapy for RMC was not beneficial in improving survival outcomes.


Assuntos
Adenocarcinoma Mucinoso , Neoplasias Retais , Humanos , Radioterapia Adjuvante , Estadiamento de Neoplasias , Programa de SEER , Análise de Sobrevida , Neoplasias Retais/radioterapia , Neoplasias Retais/patologia , Adenocarcinoma Mucinoso/radioterapia
5.
Int J Colorectal Dis ; 38(1): 235, 2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37725159

RESUMO

PURPOSE: The oncological role of adjuvant chemotherapy (ACT) remains debated in locally advanced rectal cancer (RC) after neoadjuvant therapy (NAT), especially ypI RC. In this study, we used population-based data to evaluate the benefits of ACT in stage ypI RC after NAT and surgery. Moreover, we tried to differentiate what kind of NAT (radiotherapy alone or chemoradiotherapy) was administered because this may affect the further efficacy of ACT. METHODS: All patients with stage ypI primary rectal malignancy were diagnosed in the SEER database between 2004 and 2017. The Kaplan-Meier method was applied to estimate the effects of ACT in survival analysis. Cox regression was performed to calculate the hazard ratio (HR) and the prognosis factors of survival. Propensity score matching (PSM) was used to balance the parameters between therapy groups. RESULTS: The overall cohort's median follow-up time was 105 months. For 5-year OS and CSS, there were no significant differences between the ACT ( +) and ACT (-) groups (p = 0.105; p = 0.788). However, subgroup analyses according to the kind of NAT found that ACT improved overall survival (OS) and cancer-specific survival (CSS) in patients who received neoadjuvant radiotherapy (nRT) (p < 0.001, p = 0.015). Among patients who received neoadjuvant chemoradiotherapy (nCRT), no significant survival benefits were found between the ACT ( +) and ACT (-) groups (p = 0.526, p = 0.288). CONCLUSION: Our population-based cohort study suggested that the efficacy of ACT was associated with the kind of NAT. The ACT provides survival benefits in stage ypI RC for patients who received nRT. However, among patients who received nCRT, ACT did not improve long-term survival.


Assuntos
Segunda Neoplasia Primária , Neoplasias Retais , Humanos , Estudos de Coortes , Terapia Neoadjuvante , Neoplasias Retais/terapia , Quimioterapia Adjuvante , Quimiorradioterapia
6.
Int J Colorectal Dis ; 38(1): 207, 2023 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-37542591

RESUMO

PURPOSE: The benefits of adjuvant chemotherapy remain debated rectal mucinous adenocarcinoma (MC). Our study aims to delve into the efficacy of adjuvant chemotherapy in pathologic stage III rectal MC by a large population-based database. METHODS: The Chi-square test was performed to examine the parameters between treatment groups. The overall survival (OS) and cancer-specific survival (CSS) of treatment groups were conducted by using the Kaplan-Meier method. The impact of factors on survival was assessed using Cox regression analyses. To balance the covariates and reduce the selection bias, we employed propensity score matching (PSM) to narrow the differences between treatment groups. RESULTS: The median follow-up time for overall patients was 80 months. In the pre-operative chemoradiotherapy (pre-CRT) group, patients who received adjuvant chemotherapy had significantly better 5-year OS and CSS. Multivariate analyses found that adjuvant chemotherapy was associated with better OS (p < 0.001, HR (95% CI): 0.66 (0.51-0.86)) and CSS (p = 0.012, HR (95% CI): 0.71 (0.54-0.93)). However, adjuvant chemotherapy was not an independent prognosis factor in both OS (p = 0.149, HR (95% CI): 0.76 (0.53-1.1); Supplement Table 1) and CSS (p = 0.183, HR (95% CI): 0.74 (0.48-1.15)) in patients who did not receive pre-CRT. After PSM, similar results were found in the pre-CRT and the no pre-CRT groups. CONCLUSION: In conclusion, our population-based retrospective cohort study indicates that the effects of adjuvant chemotherapy were associated with the pre-CRT status in patients with stage III rectal MC. In patients who underwent pre-CRT, the receipt of adjuvant chemotherapy was associated with better survival outcomes. Conversely, adjuvant chemotherapy does not seem to confer significant survival benefits to patients without pre-CRT.


Assuntos
Adenocarcinoma Mucinoso , Neoplasias Retais , Humanos , Estudos Retrospectivos , Estadiamento de Neoplasias , Quimioterapia Adjuvante , Neoplasias Retais/cirurgia , Quimiorradioterapia/métodos , Adenocarcinoma Mucinoso/terapia , Quimiorradioterapia Adjuvante , Resultado do Tratamento
7.
Updates Surg ; 75(5): 1161-1169, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37233966

RESUMO

Robotic surgery is widely utilized for rectal cancer. Older patients are associated with comorbidity and diminished cardiopulmonary reserve, resulting in uncertainty and reluctance to perform robotic surgery in older patients. The aim of the study was to assess the safety and feasibility of robotic surgery in older rectal cancer patients. We collected the data of patients diagnosed with rectal cancer and operated at our hospital from May 2015 to January 2021. All patients undergoing robotic surgery were classified into two groups: the old group (≥ 70 years) and young group (< 70 years). Perioperative outcomes were analyzed and compared between the two groups. Risk factors related to postoperative complications were also explored. A total of old N = 114 and young N = 324 rectal patients were enrolled in our study. Older patients were prone to exhibit comorbidity than the young and had lower body mass index and higher scores of American Society of Anesthesiologists than the young. No statistical difference was found in operative time, estimated blood loss, lymph nodes retrieved, tumor size, pathological TNM stage, hospital stay after surgery and total hospital cost between the two groups. The incidence of postoperative complications did not show difference between the two groups. On multivariate analyses, male sex and longer operative time could predict postoperative complications, whereas old age was not an independent factor for postoperative complications. After careful preoperative evaluation, robotic surgery is a technically feasible and safe procedure for older rectal cancer patients.


Assuntos
Laparoscopia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Humanos , Masculino , Idoso , Laparoscopia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Estudos de Viabilidade , Complicações Pós-Operatórias/etiologia , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Estudos Retrospectivos , Resultado do Tratamento
8.
Front Oncol ; 13: 1161742, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37143954

RESUMO

Background: The morbidity and mortality of young-onset colorectal cancer (YO-CRC) patients have been increasing in recent years. Moreover, YO-CRC patients with synchronous liver-only metastases (YO-CRCSLM) have various survival outcomes. Therefore, the purpose of this study was to construct and validate a prognostic nomogram for patients with YO-CRCSLM. Methods: The YO-CRCSLM patients were rigorously screened from the Surveillance, Epidemiology, and End Results (SEER) database in January 2010 and December 2018 and then assigned to a training and validation cohort randomly (1488 and 639 patients, respectively). Moreover, the 122 YO-CRCSLM patients who were enrolled in The First Affiliated Hospital of Nanchang University were served as a testing cohort. The variables were selected using the multivariable Cox model based on the training cohort and then developed a nomogram. The validation and testing cohort were used to validate the model's predictive accuracy. The calibration plots were used to determine the Nomogram's discriminative capabilities and precision, and the decision analysis (DCA) was performed to evaluate the Nomogram's net benefit. Finally, the Kaplan-Meier survival analyses were performed for the stratified patients based on total nomogram scores classified by the X-tile software. Results: The Nomogram was constructed including ten variables: marital status, primary site, grade, metastatic lymph nodes ratio (LNR), T stage, N stage, carcinoembryonic antigen (CEA), Surgery, and chemotherapy. The Nomogram performed admirably in the validation and testing group according to the calibration curves. The DCA analyses showed good clinical utility values. Low-risk patients (score<234) had significantly better survival outcomes than middle-risk (234-318) and high-risk (>318) patients (P < 0.001). Conclusion: A nomogram predicting the survival outcomes for patients with YO-CRCSLM was developed. In addition to facilitating personalized survival prediction, this nomogram may assist in developing clinical treatment strategies for patients with YO-CRCSLM who are undergoing treatment.

9.
Cell Death Dis ; 13(10): 848, 2022 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-36195596

RESUMO

Oxaliplatin is the main chemotherapy drug for gastric cancer (GC), but quite a few patients are resistant to oxaliplatin, which contributes to the poor prognosis of GC patients. There is therefore an urgent need to identify potential targets for reversing chemotherapy resistance in GC patients. In this study, we analyzed the tumor samples of GC patients who received neoadjuvant chemotherapy based on oxaliplatin through quantitative proteomics and identified the potential chemoresistance-related protein cellular retinoic acid binding protein 2 (CRABP2). CRABP2 was significantly upregulated in the tumor tissues of chemoresistant GC patients and was closely related to prognosis. The results of cell function experiments showed that CRABP2 can promote the oxaliplatin resistance of GC cells in vitro. Coimmunoprecipitation and GST pulldown assays showed that CRAPB2 expedited the binding of BAX and PARKIN in GC cells and facilitated the ubiquitination-mediated degradation of BAX. Furthermore, both the in vitro assay and cell-derived xenograft (CDX) in vivo model verified that CRABP2 promoted oxaliplatin resistance by inhibiting BAX-dependent cell apoptosis. Further experiments proved that the abnormally high expression of CRABP2 in oxaliplatin-resistant GC cells was affected by TET1-mediated DNA hydroxymethylation. The patient-derived xenograft (PDX) model suggested that interference with CRABP2 reversed oxaliplatin resistance in GC in vivo. In conclusion, the results of our study show that CRABP2 was a key molecule in oxaliplatin resistance regulation and could be a new target for reversing the chemoresistance of GC.


Assuntos
Neoplasias Gástricas , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , DNA , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Oxigenases de Função Mista/genética , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêutico , Proteínas Proto-Oncogênicas/metabolismo , Receptores do Ácido Retinoico/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Regulação para Cima/genética , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
11.
Cancer Res ; 82(5): 805-818, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35031573

RESUMO

Breast cancer is the most common malignancy in women worldwide. However, the mechanisms underlying breast cancer energy metabolism and progression remain obscure. Cancer cells rapidly adapt to microenvironments with fluctuating nutrient levels. Here, we characterized a long noncoding RNA (lncRNA), HOXC-AS3, which is activated upon glucose deprivation to trigger a nutrient-stress response and a switch in glucose metabolism. Upregulation of HOXC-AS3 in breast cancer was identified by in published microarray and RNA-sequencing datasets, and then confirmed by qRT-PCR in fresh breast cancer tissues. Glucose deprivation induced HOXC-AS3 overexpression in a dose- and time-dependent manner in breast cancer cells. Gain- and loss-of-function experiments in vitro and in vivo showed that HOXC-AS3 triggers energy metabolism reprogramming. ChIRP-mass spectrometry and unique molecular identifier RNA immunoprecipitation and high-throughput sequencing (UMI RIP-seq) identified binding motifs of HOXC-AS3 with SIRT6. HOXC-AS3 selectively antagonized SIRT6-mediated H3K9ac deacetylation of glycolysis-related genes. Moreover, HOXC-AS3 binding to SIRT6 prevented contact inhibition of HIF1α, leading to reprogramming of metabolic pathways. In addition, HOXC-AS3, SP1, and miR-1224-5p formed a positive feedback loop to maintain cancer-promoting signals. Furthermore, administration of anti-HOXC-AS3-motif-RNAs effectively blocked the function of HOXC-AS3, ultimately suppressing breast cancer progression. These results reveal a critical role for HOXC-AS3 in regulating the metabolic reprogramming of breast cancer cells under metabolic stress. Use of an anti-HOXC-AS3-motif RNA mixture may be a promising strategy to suppress breast cancer progression. SIGNIFICANCE: HOXC-AS3 is a low glucose-activated long noncoding RNA that triggers metabolic reprogramming in breast cancer cells to adapt to nutrient stress, identifying HOXC-AS3 as a potential therapeutic target for breast cancer treatment.


Assuntos
Neoplasias da Mama , MicroRNAs , RNA Longo não Codificante , Sirtuínas , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Glucose , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Sirtuínas/genética , Microambiente Tumoral
12.
Front Surg ; 8: 745748, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869556

RESUMO

Introduction: Gastric cancer is the fifth most commonly diagnosed tumor and is the fourth leading cause of cancer-related mortality, worldwide. Due to the low rate of early diagnosis, approximately two-thirds of patients are first diagnosed at an advanced stage. Neoadjuvant chemotherapy (NAC) is recommended for patients with advanced gastric cancer (AGC). The neutrophil-to-lymphocyte ratio (NLR), a combined inflammatory and immunogenic factor, has been universally used for predicting outcomes in AGC patients. Given that NLR is a dynamic process, in this study, we investigated the value of NLR change for the prediction of chemotherapeutic responses and prognosis in patients with AGC. Methods: We retrospectively enrolled 111 patients with AGC who underwent NAC following curative surgery. Patients were divided into two groups according to the NLR change after chemotherapy into the increased and decreased groups. Outcome measures were overall survival (OS) and disease-free survival (DFS). Univariate was calculated by Kaplan-Meier method. Multivariate analysis was performed using the Cox proportional hazards regression model. Results: Post-chemotherapy, NLR increased in 36 patients and decreased in 75 patients. After a median follow-up time of 19 months, six patients developed local recurrence, 23 developed distant recurrence, and 34 died. Patients with reduced post-chemotherapy NLR showed significantly longer OS (p < 0.001) and DFS (p < 0.001). A decrease in the NLR after NAC was an independent indicator associated with better OS (p < 0.001) and DFS (p < 0.001). Conclusions: In patients with AGC, a decrease in NLR after NAC indicated better survival. NLR change could serve as a robust indicator for the efficiency of NAC and prognostic prediction in patients with AGC.

13.
Cell Death Discov ; 7(1): 398, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34930912

RESUMO

Ubiquilin 4 (UBQLN4) is an important member of the ubiquitin-like protein family. An increasing number of studies have shown that UBQLN4 is an important regulator of tumorigenesis. Nevertheless, the biological function and detailed mechanisms of UBQLN4 in colorectal cancer (CRC) development and progression remain unclear. Here, we identified UBQLN4 upregulation in CRC tissues and it is positively associated with CRC size, TNM stage, and lymphatic metastasis. Patients with high UBQLN4 expression had a poor prognosis. Functionally, overexpression of UBQLN4 significantly promoted CRC cell proliferation, migration, and invasion, while UBQLN4 silencing elicited the opposite effect. This result was consistent with the conclusion that UBQLN4 expression correlated positively with the CRC size and lymphatic metastasis. In vivo, UBQLN4 silencing also inhibited tumor growth. Mechanistically, using gene set enrichment analysis (GSEA) and western blot experiments, we identified that UBQLN4 activated the Wnt/ß-catenin signaling pathway to upregulate ß-catenin and c-Myc expression, thereby promoting CRC proliferation, migration and invasion. A rescue experiment further verified this conclusion. Dual luciferase reporter, real-time quantitative PCR (RT-qPCR), western blot and chromatin immunoprecipitation (ChIP) assays indicated that the transcription factor CCAAT/enhancer-binding protein beta (C/EBPß) directly bound to the UBQLN4 core promoter region and activated its transcription, upregulating ß-catenin and c-Myc expression to promote CRC progression. Thus, our findings suggest that UBQLN4 is a key oncogene in CRC and may be a promising target for the diagnosis and treatment of patients with CRC.

14.
J Int Med Res ; 49(9): 3000605211010091, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34590919

RESUMO

Duodenal cavernous haemangiomas are rare, benign disorders, and massive gastrointestinal (GI) bleeding is a rare clinical condition. The present case report describes a 50-year-old male patient who presented with severe, ongoing haematochezia. A peripheral blood smear at the time of admission showed significant anaemia, and haemoglobin level was 52 g/l (normal range, 120-175 g/l). Albumin level was also low at 28 g/l (normal range, 40-55 g/l). Standard computed tomography (CT) showed mural thickening and relative lumen stenosis in the ascending (fourth) portion of the duodenum. Contrast-enhanced CT using hypotonic solution revealed the lesions to be hypervascular haemangiomas. Laparotomy and segmental duodenum resection were performed, and the first jejunal limb was anastomosed using a side-to-end technique. Histopathological examination confirmed the diagnosis of cavernous haemangioma. The patient showed marked improvement during follow-up. The present case findings emphasize that duodenal haemangioma is possible without a history of chronic anaemia, and should remain a consideration in differential diagnosis for patients presenting with massive GI bleeding. CT is useful for preoperative diagnosis of massive bleeding, and surgery with segmental resection is usually curative.


Assuntos
Anemia , Hemangioma Cavernoso , Diagnóstico Diferencial , Duodeno , Hemorragia Gastrointestinal/diagnóstico por imagem , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/cirurgia , Hemangioma Cavernoso/complicações , Hemangioma Cavernoso/diagnóstico por imagem , Hemangioma Cavernoso/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade
15.
Medicine (Baltimore) ; 100(17): e25689, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33907143

RESUMO

BACKGROUND: An increasing body of studies has investigated that genetic polymorphisms in microRNA (miRNA) may be related to susceptibility to rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, some results remain controversial. Thus, a meta-analysis was embarked on assessing whether some miRNA polymorphisms are associated with the risk of RA and SLE. METHODS: Relevant studies were acquired on PubMed, Web of Science, Cochrane Library, CNKI, and Embase electronic databases from inception to December 2019. The strength of the association of miRNA polymorphisms with the risk of RA and SLE was assessed by odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Eligible 20 articles (36 studies) involving 5 miRNAs were enrolled in the meta-analysis. For RA, the polled result showed that there was no significant relationship between miR-146a rs2910164 and RA, but subgroup analysis based on ethnicity demonstrated that CC genotype may be a genetic protect factor for RA in Caucasians (CC vs CG+GG, OR = 0.825, 95% CI: 0.684-0.996, Pz = .045, Ph = .166). Besides, statistical significance of miR-499 rs3746444 (T/C) with susceptibility to RA was observed as well in the overall population, and the association was only significant in Caucasians but not Asians. For SLE, the associations of miR-146a rs2431697 T allele/T-carrier with increased risk of SLE were observed. CONCLUSIONS: Our results highlight that miR-499 rs3746444 may contribute to RA susceptibility, particularly in Caucasians. In addition, CC genotype in miR-146a rs2910164 may act as a protector of RA in Caucasians. For SLE, miR-146a rs2431697 (C/T) is most likely to the increased the risk of SLE. These findings do not support the genetic association between miR-196a2 rs11614913 and RA/SLE susceptibility, as well as the association of miR-146a rs2910164, miR-146a rs57095329, miR-499 rs3746444 with SLE.


Assuntos
Artrite Reumatoide/genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Lúpus Eritematoso Sistêmico/genética , MicroRNAs/genética , Povo Asiático/genética , Estudos de Casos e Controles , Genótipo , Humanos , Razão de Chances , População Branca/genética
16.
Cancer Cell Int ; 20: 494, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061846

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide. Circular RNAs (circRNAs), a novel class of non-coding RNAs, have been confirmed to be key regulators of many diseases. With many scholars devoted to studying the biological function and mechanism of circRNAs, their mysterious veil is gradually being revealed. In our research, we explored a new circRNA, hsa_circ_0026416, which was identified as upregulated in CRC with the largest fold change (logFC = 3.70) of the evaluated circRNAs via analysing expression profiling data by high throughput sequencing of members of the GEO dataset (GSE77661) to explore the molecular mechanisms of CRC. METHODS: qRT-PCR and western blot analysis were utilized to assess the expression of hsa_circ_0026416, miR-346 and Nuclear Factor I/B (NFIB). CCK-8 and transwell assays were utilized to examine cell proliferation, migration and invasion in vitro, respectively. A luciferase reporter assay was used to verify the combination of hsa_circ_0026416, miR-346 and NFIB. A nude mouse xenograft model was also utilized to determine the role of hsa_circ_0026416 in CRC cell growth in vivo. RESULTS: Hsa_circ_0026416 was markedly upregulated in CRC patient tissues and plasma and was a poor prognosis in CRC patients. In addition, the area under the curve (AUC) of hsa_circ_0026416 (0.767) was greater than the AUC of CEA (0.670), CA19-9 (0.592) and CA72-4 (0.575). Functionally, hsa_circ_0026416 promotes cell proliferation, migration and invasion both in vitro and in vivo. Mechanistically, hsa_circ_0026416 may function as a ceRNA via competitively absorbing miR-346 to upregulate the expression of NFIB. CONCLUSIONS: In summary, our findings demonstrate that hsa_circ_0026416 is an oncogene in CRC. Hsa_circ_0026416 promotes the progression of CRC via the miR-346/NFIB axis and may represent a potential biomarker for diagnosis and therapy in CRC.

17.
Medicine (Baltimore) ; 99(36): e22125, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899097

RESUMO

RATIONALE: Primary gastric squamous cell carcinoma (SCC) is rarely encountered clinically. SCC, which presents as a submucosal tumor, is even rarer. Without the support of pathological evidence, it is difficult to make a correct preoperative diagnosis. Due to limited clinical data, the pathogenesis and treatment of gastric SCC remain unclear. PATIENT CONCERNS: A 69-year-old man was admitted to our hospital with unexplained weight loss. Endoscopy revealed a submucosal mass without any ulcer on its surface located on the body of the stomach. The results of 2 gastroscopic mucosal biopsies were chronic inflammation. DIAGNOSES: The clinical diagnosis by computed tomography (CT) and gastroscopy was gastrointestinal stromal tumor (GIST) preoperatively. The postoperative pathological examination demonstrated this tumor as moderately differentiated SCC. INTERVENTIONS: Total gastrectomy, distal pancreatectomy, and splenectomy were performed. OUTCOMES: The patient was discharged 7 days after the surgery without any complications. The follow-up CT scan showed no evidence of metastatic disease 6 months after surgery. LESSONS: Large primary gastric SCC could present as a submucosal mass. Gastroscopic mucosal biopsy may not be able to get tumor tissue due to inflammatory reaction.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Idoso , Carcinoma de Células Escamosas/cirurgia , Diagnóstico Diferencial , Tumores do Estroma Gastrointestinal/diagnóstico , Humanos , Masculino , Neoplasias Gástricas/cirurgia
18.
Cell Death Dis ; 11(8): 625, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32796815

RESUMO

Colorectal cancer (CRC) is a common malignant tumor with a poor prognosis. However, its pathogenesis has not been fully elucidated, accounting for poor overall survival. Circular RNA (circRNA) is a class of noncoding RNAs discovered many years ago. Only recently have they been re-evaluated for their important roles in the regulation of gene expression. Studies have confirmed that circRNAs have important biological functions in a variety of malignant tumors. This study aimed to characterize one circRNA derived from the MBOAT2 gene and termed it circMBOAT2, which has been reported to promote prostate cancer progression. CircMBOAT2 is highly expressed in both CRC tissues and serum samples, and has a correlation with tumor stage. The receiver-operating characteristic curves suggested that circMBOAT2 acted as a novel diagnostic tumor marker in CRC. Univariate and multivariate analyses showed that the levels of circMBOAT2 in tissues were independent prognostic markers of CRC. Further functional studies revealed that circMBOAT2 served as a microRNA (miRNA) sponge of miR-519d-3p and promoted the proliferation, migration, and invasion of CRC cells. Also, circMBOAT2 regulated cell proliferation and migration by competitively binding to miR-519d-3p and targeting troponin-associated protein (TROAP) in CRC cells. These results suggested that circMBOAT2 might be a novel potential biomarker of CRC.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , MicroRNAs/metabolismo , RNA Circular/metabolismo , Sequência de Bases , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Prognóstico , RNA Circular/genética , Análise de Sobrevida , Regulação para Cima/genética
19.
Pathol Oncol Res ; 26(4): 2169-2175, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32170582

RESUMO

Synchronous multiple gastric cancer (SMGC) was a special type of gastric cancer with relatively low incidence. This article was designed to demonstrate that the total tumor volume (TTV) should be treated as an important prognostic factor in SMGC patients with curative gastrectomy. This study retrospective analyzed 140 SMGC patients who received curative gastrectomy between December 2004 and December 2014 in our hospital. Clinicopathological features, preoperative evaluation, surgical treatment, and outcome parameters were reviewed and analyzed. This study applied univariate and multivariate analyses to identify the most significant prognostic factors. In the univariate analysis, the TTV, pTTVNM, pN stage, pT of main tumor were all significant prognostic factors in SMGC patients (all P < 0.05). In the multivariate analysis, pN stage, TTV and pTTVNM were confirmed to be independent prognostic factors (all P < 0.05). In the comparison of survival analysis, the pTTVNM stage system (P < 0.05) was superior to the pTNM stage system (P > 0.05) in SMGC patients. In conclusion, the TTV should be considered as an independent prognostic factor in overall survival in SMGC patients who received curative gastrectomy. The pTTVNM stage should be recommended as a suitable staging system for SMGC patients.


Assuntos
Adenocarcinoma/patologia , Gastrectomia/mortalidade , Neoplasias Primárias Múltiplas/patologia , Neoplasias Gástricas/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/cirurgia , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida , Carga Tumoral
20.
BMC Cancer ; 19(1): 797, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409315

RESUMO

BACKGROUND: To demonstrate that post-therapy pathological tumor volume (ypTV) should be considered as an independent prognostic factor in advanced gastric cancer (GC) patients who underwent neoadjuvant chemotherapy (NAC) and gastrectomy. METHODS: A total of 253 GC patients who received gastrectomy between January 2010 and December 2016 in our hospital were enrolled in this study. Clinicopathologic factors were evaluated using univariable and multivariable analysis. ypTV was calculated using π* (tumor diameter/2)2 *tumor invasion depth (cm3). RESULTS: Cut-point survival analysis demonstrated that the appropriate cut-offs for ypTV were 3, 6, 10, and 19 (cm3). Patients with tumor volumes of 0-3.0, 3.1-6.0, 6.1-10.0, 10.1-19.0, ≥19.1 cm3 were defined as ypTV1, 2, 3, 4a and 4b. Using multivariable analysis, the tumor volume (ypTV stage, P < 0.05), ypN stage (P < 0.05), response to NAC (P < 0.05), vascular invasion (P < 0.05) and ypTvNM staging (P < 0.05) were independent prognostic factors. Kaplan-Meier analysis demonstrated that the 8th AJCC/UICC ypTNM staging was not a significant predictor for survival (P > 0.05); however, our newly defined ypTvNM staging was a significant predictor for survival (P < 0.05). CONCLUSIONS: ypTV should be considered as an independent prognostic factor for GC patients after NAC. ypTvNM staging should be recommended to improve the accuracy of prognostic prediction for GC patients who received NAC plus gastrectomy.


Assuntos
Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Adulto , Idoso , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Gastrectomia , Humanos , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/terapia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Carga Tumoral
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