Colonic neoplasms

结肠肿瘤
  • 文章类型: Journal Article
    背景:ChatGPT(OpenAI)在临床诊断中显示出巨大的潜力,并可能成为临床实践中出色的辅助工具。本研究通过比较GPT-3.5和GPT-4.0在模型迭代中的性能来调查和评估ChatGPT的诊断能力。
    目的:本研究旨在评估GPT-3.5和GPT-4.0对结肠癌的精确诊断能力及其作为外科医生辅助诊断工具的潜力,并比较GTP-3.5和GPT-4.0的诊断准确率。我们精确评估主要和次要诊断的准确性,并根据7个类别分析GPT-3.5和GPT-4.0中误诊的原因:患者病史,症状,身体体征,实验室检查,影像学检查,病理检查,和术中发现。
    方法:我们从中华医学会出版社数据库检索了316例肠癌病例报告,其中286例数据清理后被认为是有效的。将案例从普通话翻译成英语,然后使用简单的方法输入GPT-3.5和GPT-4.0,直接提示引发原发性和继发性诊断。我们进行了一项比较研究,以评估GPT-4.0和GPT-3.5的诊断准确性。普外科的三位资深外科医生,专攻结直肠手术,在中国人民解放军(中国人民解放军)总医院评估诊断信息。主要和次要诊断的准确性根据预定标准进行评分。此外,我们根据7个类别分析和比较了两种模型中误诊的原因:患者病史,症状,身体体征,实验室检查,影像学检查,病理检查,和术中发现。
    结果:在286例中,GPT-4.0和GPT-3.5对初级诊断均表现出较高的诊断准确性。但GPT-4.0的准确率显著高于GPT-3.5(平均值0.972,SD0.137vs平均值0.855,SD0.335;t285=5.753;P<.001)。对于二级诊断,GPT-4.0的准确率也显著高于GPT-3.5(平均值0.908,SD0.159vs平均值0.617,SD0.349;t285=-7.727;P<.001).GPT-3.5在处理患者病史方面显示出局限性,症状表现,实验室测试,和成像数据。尽管GPT-4.0比GPT-3.5有所改善,但在识别症状和实验室测试数据方面仍然存在局限性。对于主要和次要诊断,与年龄相关的准确性没有显着差异,性别,或GPT-4.0和GPT-3.5之间的系统组。
    结论:这项研究表明,ChatGPT,特别是GPT-4.0,具有显著的诊断潜力,与GPT-4.0表现出更高的精度比GPT-3.5。然而,GPT-4.0仍然有局限性,特别是在识别患者症状和实验室数据方面,这表明需要在现实世界的临床环境中进行更多的研究,以增强其诊断能力。
    BACKGROUND: ChatGPT (OpenAI) has shown great potential in clinical diagnosis and could become an excellent auxiliary tool in clinical practice. This study investigates and evaluates ChatGPT in diagnostic capabilities by comparing the performance of GPT-3.5 and GPT-4.0 across model iterations.
    OBJECTIVE: This study aims to evaluate the precise diagnostic ability of GPT-3.5 and GPT-4.0 for colon cancer and its potential as an auxiliary diagnostic tool for surgeons and compare the diagnostic accuracy rates between GTP-3.5 and GPT-4.0. We precisely assess the accuracy of primary and secondary diagnoses and analyze the causes of misdiagnoses in GPT-3.5 and GPT-4.0 according to 7 categories: patient histories, symptoms, physical signs, laboratory examinations, imaging examinations, pathological examinations, and intraoperative findings.
    METHODS: We retrieved 316 case reports for intestinal cancer from the Chinese Medical Association Publishing House database, of which 286 cases were deemed valid after data cleansing. The cases were translated from Mandarin to English and then input into GPT-3.5 and GPT-4.0 using a simple, direct prompt to elicit primary and secondary diagnoses. We conducted a comparative study to evaluate the diagnostic accuracy of GPT-4.0 and GPT-3.5. Three senior surgeons from the General Surgery Department, specializing in Colorectal Surgery, assessed the diagnostic information at the Chinese PLA (People\'s Liberation Army) General Hospital. The accuracy of primary and secondary diagnoses was scored based on predefined criteria. Additionally, we analyzed and compared the causes of misdiagnoses in both models according to 7 categories: patient histories, symptoms, physical signs, laboratory examinations, imaging examinations, pathological examinations, and intraoperative findings.
    RESULTS: Out of 286 cases, GPT-4.0 and GPT-3.5 both demonstrated high diagnostic accuracy for primary diagnoses, but the accuracy rates of GPT-4.0 were significantly higher than GPT-3.5 (mean 0.972, SD 0.137 vs mean 0.855, SD 0.335; t285=5.753; P<.001). For secondary diagnoses, the accuracy rates of GPT-4.0 were also significantly higher than GPT-3.5 (mean 0.908, SD 0.159 vs mean 0.617, SD 0.349; t285=-7.727; P<.001). GPT-3.5 showed limitations in processing patient history, symptom presentation, laboratory tests, and imaging data. While GPT-4.0 improved upon GPT-3.5, it still has limitations in identifying symptoms and laboratory test data. For both primary and secondary diagnoses, there was no significant difference in accuracy related to age, gender, or system group between GPT-4.0 and GPT-3.5.
    CONCLUSIONS: This study demonstrates that ChatGPT, particularly GPT-4.0, possesses significant diagnostic potential, with GPT-4.0 exhibiting higher accuracy than GPT-3.5. However, GPT-4.0 still has limitations, particularly in recognizing patient symptoms and laboratory data, indicating a need for more research in real-world clinical settings to enhance its diagnostic capabilities.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    结直肠腺癌(COAD)预后较差。细胞周期蛋白依赖性激酶抑制剂2A(CDKN2A)显着影响各种人类肿瘤的发展和进展。然而,CDKN2A在COAD中的意义和病理机制仍有待阐明。我们评估了表达水平,临床意义,生物学功能,共表达基因,并使用各种数据库在COAD中富集CDKN2A的相关途径,包括阿拉巴马大学伯明翰分校癌症数据分析门户网站,基因表达谱交互式分析,肿瘤免疫评估资源,人类蛋白质图谱,STRING,遗传狂躁症,cBioPortal,和链接的组学。我们的研究表明CDKN2A在结肠腺癌中高表达(P<.001)。在正常组织中弱表达或不表达。CDKN2A高表达的结肠腺癌患者的生存时间明显短于低表达的结肠腺癌患者(P=.011)。CDKN2A在结肠腺癌组织中的表达水平与CD4+T细胞浸润呈显著正相关,巨噬细胞,和中性粒细胞。此外,CDKN2A在结肠腺癌组织中的表达水平与B细胞浸润呈显著负相关。十个hub基因包括肿瘤蛋白53,V-myc禽骨髓细胞瘤病毒癌基因同源物,AKT丝氨酸/苏氨酸激酶1,细胞周期蛋白依赖性激酶2,第10号染色体上缺失的磷酸酶和张力蛋白同源物,细胞周期蛋白D1,细胞周期蛋白依赖性激酶4,细胞周期蛋白依赖性激酶抑制剂1A,连环蛋白β1和B-Raf原癌基因,丝氨酸/苏氨酸激酶。结肠腺癌中CDKN2A基因组的突变降低了存活率。基因本体论和京都百科全书的基因和基因组分析表明,差异表达的基因富含凋亡信号通路和与代谢进程相关的多个通路。我们的结果表明,CDKN2A可以用作结肠腺癌患者预后不良的标志物。CDKN2A可能通过影响免疫细胞浸润和代谢途径调控结肠腺癌的发生发展。
    Colorectal adenocarcinoma (COAD) has a poor prognosis. Cyclin-dependent kinase inhibitor 2A (CDKN2A) significantly affects the development and progression of various human tumors. However, the significance and pathological mechanisms of CDKN2A in COAD remain to be elucidated. We assessed expression levels, clinical significance, biological function, co-expressed genes, and enrichment of related pathways of CDKN2A in COAD using various databases, including The University of Alabama at Birmingham Cancer Data Analysis Portal, Gene Expression Profiling Interactive Analysis, Tumor Immune Estimation Resource, Human Protein Atlas, STRING, GeneMANIA, cBioPortal, and Linked Omics. Our investigation showed that CDKN2A was highly expressed in colon adenocarcinomas (P < .001). It is weakly expressed or not expressed in normal tissues. The survival time of patients with colon adenocarcinoma with high CDKN2A expression is significantly shorter than that of patients with low expression levels (P = .011). There was a significant positive correlation between the expression level of CDKN2A in colon adenocarcinoma tissues and the infiltration of CD4+ T cells, macrophages, and neutrophils. Moreover, there was a significant negative association between the expression level of CDKN2A in colon adenocarcinoma tissues and B cell infiltration. The ten hub genes included tumor protein 53, V-myc Avian Myelocytomatosis Viral Oncogene Homolog, AKT serine/threonine kinase 1, cyclin-dependent kinase 2, phosphatase and tensin homolog deleted on chromosome ten, cyclin D1, cyclin dependent kinase 4, cyclin dependent kinase inhibitor 1A, catenin beta 1, and B-Raf proto-oncogene, serine/threonine kinase. Mutations in the CDKN2A genome in colon adenocarcinoma reduce survival. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the differentially expressed genes were enriched in apoptotic signaling pathways and multiple pathways related to metabolic progression. Our results indicate that CDKN2A can be used as a marker of poor prognosis in patients with colon adenocarcinoma. CDKN2A may regulate the occurrence and development of colon adenocarcinomas by influencing immune cell infiltration and metabolic pathways.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    焦亡相关基因有很大的预后潜力,在结直肠腺癌(COAD)中尚未发现基于焦亡基因的准确预后模型.此外,基因表达特征和肿瘤免疫微环境与COAD预后相关的机制尚不清楚。构建基于焦亡相关基因的预后模型,并揭示与基因表达特征和肿瘤微环境相关的预后相关机制。收集了59个与细胞凋亡相关的基因。COAD的基因表达数据和临床数据从癌症基因组图谱下载。从基因表达综合数据库下载外部验证数据集。使用单变量和LASSOCox获得了10个具有预后价值的特征基因。构建10基因Riskscore预后模型。基因集富集分析和网络传播方法均用于寻找导致不同预后风险的途径和关键基因。ROC曲线下面积用于评价模型区分高危和低危患者的性能,1-的结果分别为0.718、0.672和0.669,3-,和5年生存时间。基于Riskscore和临床特征的列线图显示了1年、3年和5年生存率。校准曲线显示了预测和实际观测之间的良好一致性,其C指数为0.793。决策曲线表明,列线图的净收益明显优于其他单变量。获得了导致不同预后风险的四个关键途径。具有预后价值的六个关键基因,从所有4个关键通路的基因集获得高/低风险组之间的显著表达差异(P<.05)和显著生存差异(P<.05)。本研究使用10个具有预后价值的焦亡相关基因构建了COAD的预后模型。这项研究还揭示了高危组和低危组之间特定途径和肿瘤免疫微环境(TME)的显着差异,强调了ALDH5A1和Wnt信号在促进COAD中的作用以及IL-4/IL-13通路和RORC对COAD的抑制作用。该研究将有助于精确治疗。
    Pyroptosis-related genes have great potential for prognosis, an accurate prognostic model based on pyroptosis genes has not been seen in Colorectal adenocarcinoma (COAD). Furthermore, understanding the mechanisms of gene expression characteristics and the Tumor Immune Microenvironment associated with the prognosis of COAD is still largely unknown. Constructing a prognostic model based on pyroptosis-related genes, and revealing prognosis-related mechanisms associated with the gene expression characteristics and tumor microenvironment. 59 pyroptosis-related genes were collected. The gene expression data and clinical data of COAD were downloaded from The Cancer Genome Atlas. External validation datasets were downloaded from the Gene Expression Omnibus database. 10 characteristic genes with prognostic values were obtained using univariate and LASSO Cox. 10-gene Riskscore prognostic model was constructed. Both gene set enrichment analysis and network propagation methods were used to find pathways and key genes leading to different prognostic risks. The area under the ROC curves were used to evaluate the performance of the model to distinguish between high-risk and low-risk patients, the results were 0.718, 0.672, and 0.669 for 1-, 3-, and 5-year survival times. A nomogram based on Riskscore and clinical characteristics showed the probability of survival at 1, 3, and 5 years, and the calibration curves showed good agreement between the predicted and actual observations, its C-index is 0.793. The decision curves showed that the net benefit of the nomogram was significantly superior to that of the other single variables. Four key pathways leading to different prognostic risks were obtained. Six key genes with prognostic value, significant expression differences (P < .05) and significant survival differences (P < .05) between high/low risk groups were obtained from the gene set of all 4 key pathways. This study constructed a prognostic model for COAD using 10 pyroptosis-related genes with prognostic value. This study also revealed significant differences in specific pathways and the tumor immune microenvironment (TME) between the high-risk group and the low-risk group, highlighted the roles of ALDH5A1 and Wnt signaling in promoting COAD and the suppressive effects of the IL-4/IL-13 pathway and RORC on COAD. The study will be helpful for precision therapy.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    目的:观察性研究表明,在一些结肠癌患者中,D3淋巴结清扫术与改善无病生存率之间存在联系。然而,需要高质量的随机对照试验来证实其优于D2淋巴结清扫术.对D3潜在并发症的担忧限制了其在日本以外的使用。与已建立的D2程序相比,本研究检查了右侧结肠癌D3淋巴结切除术后的短期结果。材料和方法:这项回顾性队列单中心研究分析了在2019年1月至2022年11月期间在我们的医疗保健信托范围内接受根治性手术的右侧结肠癌患者的数据。仅将由常规进行D3淋巴结清扫术的外科医生治疗的患者纳入同质研究人群。执行D3的决定由手术外科医生自行决定。数据是从纸质图表和电子病历中收集的。采用非参数统计检验进行数据分析。结果:共有214例患者符合标准,170例接受D2淋巴结清扫术,44例接受D3淋巴结清扫术。两组间手术时间无显著差异,失血,术后血红蛋白水平,或输血需要。有趣的是,D3组的并发症发生率(25%)低于D2组(41.2%).然而,D3组淋巴结扩散率也较高(45.5%vs.D2的30.6%)和更多的淋巴结切除(19[16,25]vs.23[18,28])。重要的是,两组肿瘤完全清除率相似.结论:这项研究表明,D3淋巴结清扫术治疗右半结肠癌可能是安全的,具有潜在的益处。特别是对于怀疑淋巴结受累的年轻患者。然而,有限的样本量需要更大,随机试验证实了这些发现,并可能确立D3淋巴结清扫术作为标准治疗。
    OBJECTIVE: Observational studies suggest a link between D3 lymphadenectomy and improved disease-free survival in some colon cancer patients. However, high-quality randomized controlled trials are needed to confirm its advantage over D2 lymphadenectomy. Concerns about potential complications with D3 have limited its use outside of Japan. This study examines short-term outcomes following D3 lymphadenectomy for right-sided colon cancer compared to the established D2 procedure. Materials and Methods: This retrospective cohort single center study analyzed data on patients with right-sided colon cancer who underwent curative surgery within our healthcare trust between January 2019 and November 2022. Only patients treated by surgeons who routinely perform D3 lymphadenectomy were included for a homogenous study population. The decision to perform D3 was at the discretion of the operating surgeon. Data were collected from both paper charts and electronic medical records. Non-parametric statistical tests were used for data analysis. Results: A total of 214 patients met the criteria, with 170 undergoing D2 lymphadenectomy and 44 undergoing D3 lymphadenectomy. There were no significant differences between the groups in terms of surgery duration, blood loss, postoperative hemoglobin levels, or transfusion needs. Interestingly, the D3 group had a lower complication rate (25%) compared to the D2 group (41.2%). However, the D3 group also had a higher rate of lymph node spread (45.5% vs. 30.6% for D2) and more lymph nodes removed (19 [16, 25] vs. 23 [18, 28]). Importantly, both groups achieved similar complete tumour removal rates. Conclusions: This study suggests D3 lymphadenectomy for right-sided colon cancer might be safe with potential benefits, especially for younger patients with suspected lymph node involvement. However, the limited sample size necessitates larger, randomized trials to confirm these findings and potentially establish D3 lymphadenectomy as standard care.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Case Reports
    结肠淋巴瘤是一种罕见的胃肠道恶性肿瘤,可以通过特殊和严重的并发症:肠梗阻来发现。治疗基于手术和化疗。我们在这里报告一例弥漫性结肠大B细胞淋巴瘤,该病例是通过闭塞发现的,并根据手术标本的检查进行诊断的,该患者经过六个疗程的R-CHOP完全缓解。
    Colonic lymphoma is a rare malignant gastrointestinal tumor that can be revealed by an exceptional and serious complication: intestinal obstruction. Treatment is based on surgery and chemotherapy. We here report a case of diffuse colonic large B-cell lymphoma revealed by occlusion and diagnosed based on the examination of surgical specimen in a 64-year-old man who was in complete remission after six courses of R-CHOP.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Case Reports
    Pembrolizumab和其他免疫疗法已成为治疗转移性结肠癌的核心,对错配修复缺陷患者特别有效。我们报告了一例涉及一名男子的病例,他最初于2011年4月27日接受了乙状结肠癌的根治性手术,随后于2017年9月21日进行了肝肿瘤切除术。手术后,患者接受CAPEOX方案辅助化疗8个周期,并通过CT和MRI扫描进行定期监测.2022年8月24日,检测到肝转移,由于MSH2和EPCAM基因的种系突变,他被诊断出患有Lynch综合征(LS)。他于2022年9月2日每三周开始静脉注射200mg派姆单抗治疗,并表现出持续的反应。然而,经过17个周期,他出现了胰腺内分泌功能障碍的治疗相关不良事件(TRAE),导致1型糖尿病,皮下注射胰岛素。经过30个周期的治疗,没有观察到疾病的证据。该病例强调了一线pembrolizumab在治疗与LS相关的结肠癌肝转移中的显着临床益处。尽管发生了TRAE。它提出了关于完全或部分反应后免疫疗法的最佳持续时间以及是否应在TRAE紧急情况下停止治疗的关键问题。持续的研究和即将进行的检查点抑制剂的临床试验有望完善LS相关癌的治疗方案。
    Pembrolizumab and other immunotherapies have become central in treating metastatic colon cancer, particularly effective in patients with mismatch repair deficiencies. We report a case involving a man who initially underwent radical surgery for sigmoid colon cancer on April 27, 2011, followed by hepatic tumor resection on September 21, 2017. Post-surgery, he received eight cycles of adjuvant chemotherapy with the CAPEOX regimen and was regularly monitored through CT and MRI scans. On August 24, 2022, liver metastases were detected, and he was diagnosed with Lynch syndrome (LS) due to germline mutation in the MSH2 and EPCAM genes. He commenced treatment with 200mg of pembrolizumab intravenously every three weeks on September 2, 2022, and demonstrated a sustained response. However, after 17 cycles, he developed a treatment related adverse event (TRAE) of pancreatic endocrine dysfunction, leading to type 1 diabetes, managed with subcutaneous insulin injections. After 30 cycles of treatment, no evidence of disease was observed. This case underscores the significant clinical benefits of first-line pembrolizumab in managing hepatic metastasis in colonic carcinoma associated with LS, despite the occurrence of TRAEs. It raises critical questions regarding the optimal duration of immunotherapy following a complete or partial response and whether treatment should be discontinued upon the emergency of TRAEs. Continued research and forthcoming clinical trials with checkpoint inhibitors are expected to refine treatment protocols for LS-associated carcinoma.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    一个80多岁有充血性心力衰竭病史的女人,房性心律失常治疗房室结消融和永久性起搏器(PPM)放置,接受修复后的二尖瓣疾病状态和治疗后的结肠癌状态,以进一步评估劳累时严重呼吸困难。成像显示人工二尖瓣和PPM导线上都有植被。收集没有生长的血培养物,所以进行了无细胞DNAKarius测试,可以检测1000多种病原体,灵敏度在87%至93%之间。鉴于牛链球菌亚种巴氏杆菌与结直肠癌的关系,检测结果呈阳性,进行了腹部成像和内窥镜活检,显示结肠恶性肿瘤复发。患者在心脏介入之前接受了右结肠切除术。该报告描述了新型无细胞DNAKarius测试的临床应用,这导致了与巴斯德氏杆菌心内膜炎相关的复发性结肠癌的诊断。
    A woman in her 80s with a history of congestive heart failure, atrial arrhythmia treated with atrioventricular nodal ablation and permanent pacemaker (PPM) placement, mitral valve disease status post-repair and colon cancer status post-treatment was admitted for further evaluation of severe dyspnea on exertion. Imaging revealed vegetation on both the prosthetic mitral valve and the PPM lead. Blood cultures were collected without growth, so a cell-free DNA Karius test was performed, which can detect over 1000 pathogens and has a sensitivity between 87% and 93%. Testing returned positive results for Streptococcus bovis subspecies pasteurianus Given its association with colorectal cancer, abdominal imaging and an endoscopic biopsy were performed, showing recurrent colonic malignancy. The patient underwent a right colon resection prior to cardiac intervention. This report describes the clinical application of the novel cell-free DNA Karius test, which led to the diagnosis of recurrent colon cancer associated with S. pasteurianus endocarditis.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    光疗是一种有前途的抗肿瘤方式,其中包括光热疗法(PTT)和光动力疗法(PDT)。然而,肿瘤局部缺氧极大地阻碍了光疗的疗效,吲哚胺2,3-双加氧酶(IDO)和程序性细胞死亡配体-1(PD-L1)在肿瘤细胞上的过表达。为了解决这些问题,自组装多功能聚合物胶束(RIMNA)被开发用于共同递送光敏剂吲哚菁绿(ICG),氧合器MnO2,IDO抑制剂NLG919和toll样受体4激动剂单磷酰脂质A(MPLA)。值得注意的是,RIMNA聚合物胶束具有良好的稳定性,均匀的形态,优越的生物相容性,并加强PTT/PDT效应。更重要的是,RIMNA介导的IDO抑制与程序性死亡受体1(PD-1)/PD-L1阻断相结合,显着改善了免疫抑制并促进了免疫激活。基于RIMNA的光免疫疗法与PD-1抗体协同作用可显著抑制原发肿瘤增殖,以及刺激免疫力,极大地抑制肺转移和远处肿瘤的生长。这项研究提供了一种有效的方法来加强光疗的疗效和减轻免疫抑制,从而为癌症治疗带来临床益处。
    Phototherapy is a promising antitumor modality, which consists of photothermal therapy (PTT) and photodynamic therapy (PDT). However, the efficacy of phototherapy is dramatically hampered by local hypoxia in tumors, overexpression of indoleamine 2,3-dioxygenase (IDO) and programmed cell death ligand-1 (PD-L1) on tumor cells. To address these issues, self-assembled multifunctional polymeric micelles (RIMNA) were developed to co-deliver photosensitizer indocyanine green (ICG), oxygenator MnO2, IDO inhibitor NLG919, and toll-like receptor 4 agonist monophosphoryl lipid A (MPLA). It is worth noting that RIMNA polymeric micelles had good stability, uniform morphology, superior biocompatibility, and intensified PTT/PDT effect. What\'s more, RIMNA-mediated IDO inhibition combined with programmed death receptor-1 (PD-1)/PD-L1 blockade considerably improved immunosuppression and promoted immune activation. RIMNA-based photoimmunotherapy synergized with PD-1 antibody could remarkably inhibit primary tumor proliferation, as well as stimulate the immunity to greatly suppress lung metastasis and distant tumor growth. This study offers an efficient method to reinforce the efficacy of phototherapy and alleviate immunosuppression, thereby bringing clinical benefits to cancer treatment.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    目的:本研究的目的是探讨核受体亚家族3C组成员2(NR3C2)与结肠癌预后之间的潜在相关性,以及这种关联背后的机制。
    方法:从癌症基因组图谱(TCGA)数据库检索与结肠癌有关的mRNA(信使RNA)数据和临床记录。使用R软件分析正常结肠和肿瘤组织之间的NR3C2表达差异。此外,我们还研究了NR3C2表达与预后的关系,病理参数。通过生物信息学方法进一步预测NR3C2的相对作用,并采用受试者工作特征(ROC)曲线评价NR3C2在结肠癌中的诊断价值。来自GEO(基因表达综合)数据库中的结肠癌样品的单细胞数据进一步研究了与NR3C2失调相关的较低存活率的机制。测定三个新鲜结肠癌样品和它们各自的副癌样品中的NR3C2表达。此外,通过慢病毒载体转染构建过表达NR3C2和敲低NR3C2的结肠癌细胞模型。细胞计数试剂盒-8测定,裸鼠移植肿瘤和transwell试验用于检查增殖,结肠癌细胞的迁移和侵袭。对Wnt/β-catenin通路的影响,通过评估几种关键蛋白的表达水平来检测细胞自噬和细胞凋亡的活性,包括Bcl-2,Bax,LC3
    结果:我们发现NR3C2在结肠癌组织中的水平明显低于癌旁组织,与远处和淋巴转移有关,临床分期,和不良的临床结果,是结肠癌的独立预后因素和潜在标志物。单细胞转录组数据鉴定了高表达NR3C2的循环T和B细胞亚群,该细胞参与TNF信号通路。功能实验表明NR3C2的下调导致Wnt/β-catenin信号通路的激活,并在抑制细胞自噬和凋亡的同时促进结肠癌细胞的增殖和侵袭。
    结论:NR3C2可能通过调控Wnt/β-catenin影响细胞增殖,结肠癌侵袭性细胞凋亡和自噬,该轴是结肠癌治疗的潜在靶点。
    OBJECTIVE: The aim of this study was to explore the potential correlation between the nuclear receptor subfamily 3 group C member 2 (NR3C2) and outcomes of colon cancer, along with the mechanisms underlying this association.
    METHODS: mRNA (messenger RNA) data and clinical records pertaining to colon cancer were retrieved from The Cancer Genome Atlas (TCGA) database. The analysis of NR3C2 expression discrepancies between normal colon and tumor tissues was conducted using R software. In addition, we also studied the relationship between NR3C2 expression and prognosis, pathological parameters. The relative role of NR3C2 were further predicted through bioinformatics methods and receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of NR3C2 in colon cancer. Single-cell data from colon cancer samples in the GEO (Gene Expression Omnibus) database further investigated the mechanism of the lower survival associated with NR3C2 dysregulation. NR3C2 expression in three fresh colon cancer samples and their respective paracancer samples was determined. Furthermore, colon cancer cell models overexpressing NR3C2 and with knockdown NR3C2 were constructed by lentiviral vector transfection. Cell Counting Kit-8 assay, transplantation of tumors in nude mice and transwell assays were used to examine the proliferation, migration and invasion of colon cancer cells. The effect on the Wnt/β-catenin pathway, activities of cellular autophagy and cell apoptosis were examined by assessing the expression levels of several key proteins, including Bcl-2, Bax, and LC3.
    RESULTS: We found that NR3C2 was found a significantly lower level in colon cancer tissues than in adjacent tissues, which was associated with distant and lymphatic metastases, clinical stage, and poor clinical outcome, and it was an independent prognostic factor and potential marker of colon cancer. Single-cell transcriptome data identified the subset of circulating T and B cells with high expression of NR3C2, which is involved in TNF signaling pathway. Functional experiments show that downregulation of NR3C2 resultsed in the activation of the Wnt/β-catenin signaling pathway, and promotesd the proliferation and invasion of colon cancer cells while suppressing cell autophagy and apoptosis.
    CONCLUSIONS: NR3C2 may regulate Wnt/β-catenin to affect the proliferation, invasion apoptosis and autophagy of colon cancer, and this axis is a potential target for the treatment of colon cancer.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Case Reports
    一位60多岁的相对健康的男性患者除了前几个月体重明显下降外,还表现出胸痛和呼吸急促。他被送进医院,并接受了CT肺血管造影检查,没有显示肺栓塞,但由于异常发现,他随后进行了超声和CT扫描。他的CT显示中横结肠有些增厚,and,此外,大量肝转移被描述为无数,可能取代了大部分肝脏。最初,他的肝功能测试只是在演讲中有点混乱。进行了柔性乙状结肠镜检查,并确定了横结肠恶性肿瘤并进行了活检,表现为肺外小细胞癌(EPSCC)。他因新诊断的转移性小细胞结肠癌而接受紧急化疗;他在第一次化疗后出现了肿瘤溶解综合征。此后他继续拒绝,并在入院后不久死亡。转移性小细胞结肠癌是一种罕见的诊断,由于缺乏驱动治疗策略的试验证据,因此具有挑战性。治疗主要遵循肺小细胞癌途径。我们,因此,介绍一例结肠EPSCC病例,概述本病的诊断和治疗策略.
    A relatively healthy male patient in his 60s presented with chest pain and shortness of breath in addition to a history of significant weight loss over the preceding months. He was admitted to the hospital and investigated with a CT pulmonary angiogram, which did not demonstrate a pulmonary embolus, but he subsequently went on to have an ultrasound and CT scan because of abnormal findings. His CT demonstrated some thickening of the mid-transverse colon, and, in addition, large volume liver metastases described as innumerable and probably replacing most of the liver.Initially, his liver function tests were only mildly deranged at the presentation. Flexible sigmoidoscopy was performed, and a transverse colonic malignancy was identified and biopsied, which demonstrated an extrapulmonary small cell carcinoma (EPSCC). He was admitted for urgent chemotherapy for newly diagnosed metastatic small-cell colonic cancer; he developed tumour lysis syndrome following his first dose of chemotherapy. He continued to decline following this and died soon after his admission. Metastatic small-cell colonic cancer is a rare diagnosis which is challenging to manage due to the lack of trial evidence to drive treatment strategies. The management largely follows the pulmonary small cell cancer pathway. We, therefore, present a colonic EPSCC case outlining the diagnostic and treatment strategies for this disease.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

公众号