基于铁死亡相关基因构建肝细胞癌的预后模型

目的 肝细胞癌是最常见的恶性肿瘤之一,具有预后差、复发率高的特点.铁死亡是最近发现的一种铁依赖性的细胞程序性死亡的形式,不同于细胞坏死、细胞凋亡、细胞自噬,由脂质过氧化驱动.该研究探讨了铁死亡相关基因与肝细胞癌患者预后之间的关系.方法 从公共数据库中下载肝细胞癌患者的基因表达及相应的临床病理数据.使用单因素COX回归分...     

铁死亡机制在胰腺癌中的研究现状及未来展望

目的 了解铁死亡的分子机制及它在胰腺癌中的研究进展及未来展望。方法 查阅铁死亡分子机制及它与胰腺癌发生及发展相关的基础和临床应用研究方面的文献并进行综述。结果 铁死亡是一种依赖铁聚集的非凋亡型细胞死亡形式,其分子生物学特点包括铁离子过载、活性氧堆积、脂质过氧化等。铁死亡与细胞代谢密切相关,胰腺癌在发生、发展过程中也存在因代谢异常引起的铁死亡失衡,进而引发胰腺癌细胞异常增殖而导致其进展。通过对铁死亡的关键分子信号通路进行调控,有望为胰腺癌治疗寻找新的药物治疗靶点及治疗途径,目前已有铁死亡的相关研究结果展现出了未来在胰腺癌治疗领域进行转化研究的潜力。结论 铁死亡机制在胰腺癌研究中具有重要的价值。目前对于铁死亡的研究仍有许多未知的领域,对于其中的分子机制仍知之甚少。未来随着对于铁死亡研究的不断深入,有望为胰腺癌治疗提供新思路并发掘新的药物研发靶点。     

基于铁死亡相关基因表达构建肝细胞癌患者临床预后模型

目的 肝细胞癌（hepatocellular carcinoma,HCC）是全球癌症死亡的重要原因。本研究旨在探讨肝细胞癌中铁死亡相关基因的预后预测能力,构建基于铁死亡相关基因的风险预测模型,并初步研究铁死亡相关基因在肝移植缺血/再灌注损伤中的表达改变。方法 本研究利用从TARGET数据库获得的转录数据进行生物信息学分析,采用COX回归和共识聚类法鉴定了2个基于铁死亡相关基因的肝细胞癌分子亚群。进一步通过对两个分子亚群差异表达基因的通路富集分析,探索铁死亡参与肝细胞癌预后的可能机制。然后,我们进行了LASSO-COX回归分析,以建立风险预测模型,并评估模型的可靠性。通过对GEO数据库中转录组数据进行差异表达基因分析,初步探索肝移植缺血/再灌注损伤中铁死亡相关基因表达改变。结果 我们根据铁死亡相关基因的不同表达谱确定了两个具有不同总生存期的肝细胞癌分子亚群。两个分子亚群之间差异表达基因通路富集到免疫和胆汁酸代谢相关通路。最终我们构建了基于6个铁死亡相关基因KLF2、MYCN、FZD7、PRDX6、HILPDA、SLC7A11的风险模型,并使用列线图进行模型的可视化,模型评估显示该模型对肝...     

双硫死亡相关基因与胰腺癌预后及免疫治疗的关系探索:基于生物信息学分析

目的 探讨双硫死亡相关基因(disulfidptosis-related genes,DRGs)与胰腺癌患者预后及免疫治疗反应的关系。方法 从癌症基因组图谱中下载胰腺癌患者的转录组数据、体细胞突变数据及对应的临床信息,从已知的15个DRGs中筛选出在胰腺癌中发生突变的DRGs,通过共识聚类算法识别出DRGs亚型,然后分析识别出的DRGs亚型与胰腺癌患者预后、免疫细胞浸润和功能富集通路的关系,进一步根据DRGs基因表达量进行风险评分并根据风险评分的均值将患者分为高风险(≥均值)和低风险(<均值)组,比较DRGs不同亚型患者的风险评分及总生存情况,同时评估风险评分与患者预后及肿瘤突变负荷的关系。结果 从癌症基因组图谱中下载了177例胰腺癌患者的转录组数据和对应的临床信息,其中有161例含有体细胞突变数据,共筛选出10个DRGs在胰腺癌中发生突变,共识聚类算法识别出2个DRGs亚型即A亚型和B亚型。A亚型胰腺癌患者的总生存情况优于B亚型胰腺癌患者(χ²=8.316,P=0.003),A亚型胰腺癌患者具有更高的免疫细胞浸润丰度,在代谢和传导相关通路上显著富集。177...     

基于双硫死亡相关基因的胃癌预后预测模型的构建及验证

目的 构建基于双硫死亡相关基因的胃癌预后预测模型。方法 首先,从TCGA数据库和GEO数据库获取转录组数据和临床数据,探索双硫死亡相关基因在胃癌组织和正常组织的表达情况及其表达对胃癌患者总生存期（overall survival,OS）的影响。之后,通过一致性聚类确定两个双硫死亡相关基因簇,利用LASSO回归进一步筛选关键基因,并采用多因素Cox比例风险回归构建OS预测模型。结果 在24个双硫死亡相关基因中,有16个在胃癌患者的表达与正常组织的差异具有统计学意义（P<0.05）,单因素Cox比例风险回归结果显示有9个与OS相关（P<0.05）。使用基于24个双硫死亡相关基因的共识聚类,将所有样本分为2类,该2个聚类间有299个差异表达基因。在训练集中,利用LASSO回归确定了其中14个基因用于构建OS预测模型,计算风险评分,结果高风险组的OS差于低风险组（P<0.05）,该预测模型在验证集中也有较高的曲线下面积值。结论 基于双硫死亡相关基因构建的OS预测模型可以预测胃癌患者的预后。     

胰腺癌预后相关因素的分析研究

目的研究胰腺癌临床相关因素与预后的关系.方法：回顾性分析115例胰腺癌患者相关临床资料,进行是否影响预后的单因素方差分析,符合条件的纳入Cox比例风险模型进行多因素分析.结果：胰腺癌患者的预后与性别、糖尿病史、胰腺炎病史、肿瘤家族史、肿瘤部位、CA19-9异常无明显相关（P〉 0.05）;而与初诊原因、肿瘤大小、临床分期、胰周侵犯、远处转移、治疗方法、CEA是否异常有关（P〈 0.05）.其中初诊原因、肿瘤分期、胰周侵犯、远处转移、治疗方法与预后关系最密切（P〈 0.01）.结论：早期发现、根治性手术是改善胰腺癌预后最关键因素,TNM临床分期是判断预后的最可靠依据,血清CEA可评价胰腺癌疾病进展程度.     

早期死亡风险评分对胰腺癌患者术后预后预测的价值

目的探讨早期死亡风险评分(early mortality risk score,EMRS)对胰腺癌患者术后预后的预测价值,寻找胰腺癌术后预后不良的早期预测方法。方法收集就诊并接受根治性手术治疗的370例胰腺癌患者的临床资料,记录患者的性别,年龄,体质指数(BMI),肿瘤部位、大小,合并基础疾病情况,术后生存时间,EMRS评分结果等信息。根据患者术后1年的临床结局(生存,死亡)将患者分为生存组和死亡组。单因素分析法比较组间上述指标的差异,选取单因素分析当中有差异的指标进一步进行Logistic多元回归分析,以确定胰腺癌患者术后预后不良的相关危险因素,并评价EMRS对胰腺癌患者术后预后的预测价值。结果本组370例患者,根据随访1年时的临床结局分为生存组(252例)和死亡组(118例),两组患者平均年龄、性别构成、合并基础疾病、既往吸烟史、近期体重变化、肿瘤分化程度、是否合并淋巴结转移、周围神经转移、血管转移、及术后并发症发生率比较,差异无统计学意义(P0.05);死亡组患者肿瘤相对较大,切缘阳性率、平均EMRS评分较高,组间比较差异有统计学意义(P0.05);且肿瘤大小,切缘阳性率、EMRS评分3项指标进行多元Logistic回归分析,结果显示,该3项指标均为胰腺癌患者术后早期预后不良的独立危险因子(OR均1.0,P均0.05);在EMRS=3.0时,其预测患者术后早期预后不良的敏感性和特异性分别为77.4%和82.3%。结论 EMRS与胰腺癌患者术后早期预后有关,高EMRS评分是胰腺癌患者术后早期预后不良的独立危险因子,EMRS评分3时,其预测胰腺癌患者术后早期预后不良的敏感性和特异性均较高。     

铁死亡在胰腺癌中的作用研究及进展

胰腺癌是一种恶性程度极高的消化系统肿瘤,侵袭性强,早期诊断困难,大多数患者因确诊时已处于晚期而无法接受根治性手术治疗,亦无其他有效治疗手段,故预后极差。铁死亡是一种铁依赖性新型细胞程序性死亡方式,以细胞内铁过载、脂质过氧化物增多和活性氧异常蓄积为特征。近年研究发现铁死亡在抑制胰腺癌细胞生长、增殖方面具有重要作用,并能够提高化疗药物疗效,有望成为胰腺癌治疗的潜在靶点。笔者对铁死亡在胰腺癌发生发展及治疗中的作用研究进展作一综述。     

海德堡胰腺癌预后评分对胰腺癌根治性切除术后病人预后的评估价值分析

目的 探讨海德堡胰腺癌预后（HELPP）评分对胰腺癌根治性切除术后病人预后的评估价值。方法 回顾性分析2019年3～12月在南京大学医学院附属鼓楼医院肝胆胰中心接受根治性手术的35例胰腺癌病人的临床资料和随访资料。根据术前HELPP评分将病人分为低分组（≤3分）和高分组（>3分）,比较两组病例临床病理资料,绘制生存曲线并比较两组病人的术后生存时间差异。结果 35例病人中,低分组有21例,高分组有14例,两组病人在性别、年龄、肿瘤部位、肿瘤大小、病理学分期、是否合并糖尿病、是否行辅助治疗以及R0切除率等方面比较差异均无统计学意义。所有病人均有完整随访资料,中位随访时间为29.0个月。低分组和高分组术后中位总生存期分别为29.0个月和15.0个月,差异有统计学意义（P<0.05）。结论 术前HELPP评分可考虑作为预测根治性切除胰腺癌病人预后的工具,评分高可能提示预后不良,但仍需进一步扩大样本量进行验证。     

通过累积存活曲线分析胰腺癌术后早期死亡的预后因素

在进展期胰腺癌术后早期阶段存活率的研究中，生存曲线被描绘为一条陡直曲线。该研究的目的在于鉴别胰腺癌术后早期死亡的相关因素。方法：共研究37例病人，均经胰腺癌扩大根治术联合术中放疗治疗。通过Kaplan—Meier存活曲线来描绘累积存活曲线。假定有两条不同的曲线，另一条位于临界点以上，一条位于临界点以下，曲线的每一部分均用指数分来描绘。曲线中有3个参数，包括临界点、临界点下的高危率和临界点上的低危率，通过最大相似方法进行评估，通过单变量和多变量的危险比例回归分析对与早期死亡相关的预后因素进行评估。     

胰腺癌65例术后预后因素分析

目的探讨胰腺癌术后预后相关因素。方法收集2011年12月到2015年6月皖南医学院弋矶山医院65例胰腺癌临床资料并进行回顾性分析。结果 65例患者术后中位生存时间12.1个月,1、3、5年生存率分别为41.5%、8.2%、2.1%。单因素分析显示,淋巴结转移、CA19-9、肿瘤大小、分化程度、血管侵犯、神经侵犯为影响胰腺癌预后的因素(P0.05)。多因素分析显示,淋巴结转移、肿瘤大小、分化程度、血管侵犯、神经侵犯为影响胰腺癌预后的独立危险因素。结论胰腺癌预后受多种因素影响,其中淋巴结转移、肿瘤大小、分化程度、血管侵犯、神经侵犯可作为评估胰腺癌预后的重要指标。     

Establishment of a novel prognostic prediction model through bioinformatics analysis for prostate cancer based on ferroptosis-related genes and its application in immune cell infiltration

BackgroundFerroptosis-related genes (FRGs) play vital roles in survival and prognosis of prostate cancer (PCa) patients. We establish a ferroptosis-related prediction model through bioinformatics analysis for overall survival (OS) and disease-free survival (DFS), so as to evaluate the clinical survival status through the characteristics of immune cell infiltration (ICI), which could provide information for treatment monitoring.MethodsAt first, 268 FRGs were obtained from previous studies. Differentially expressed FRGs were identified based on The Cancer Genome Atlas (TCGA) database, and FRG enrichment analysis was performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We then performed univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses to establish OS- and DFS-related prognostic prediction models. The association of the model and clinicopathological features was further analyzed. Subsequently, unique genomic signatures of immune cell subsets were obtained through the KEGG database. Based on specific genes associated with ferroptosis and their association with ICI, immune infiltration was assessed in patients in different risk groups.ResultsWe constructed an OS- and an DFS-prognostic model through bioinformatics analysis. The predicted values of OS and DFS-related models were higher in T3–4 than in T1–2 (P=0.0057, P<0.001), and the predicted value of the DFS model in N0 stage was higher than that in N1 stage (P=0.0136). Results of Single-sample gene set enrichment analysis (ssGSEA) on the basis of the KEGG dataset showed p53 signaling being the most enriched signal in the high-risk group, while endocytosis was the most enriched signal in the low-risk group. M2 macrophages (P=0.007) and neutrophils (P=0.024) were enriched in the high-risk group, and CD4-activated memory T cells were significantly accumulated in the low-risk group (P=0.017).ConclusionsThe OS- and DFS-related model based on FRGs and ICI create new insights into the disease state assessment of PCa patients., which may aid in the development of individualized and precise treatment in the future.     

LAMA3在胰腺癌中的表达及其临床意义

目的 探讨层粘连蛋白3（laminin 3,LAMA3）在胰腺癌患者中的表达,并分析其临床意义。方法 采用回顾性分析法收集温州医科大学定理临床学院2011年5月至2018年12月胰腺癌病例40例,利用免疫组化、qRT-PCR、Western blotting等方法检测胰腺癌患者手术切除癌组织及癌旁正常组织的LAMA3表达情况,分析LAMA3表达与临床病理特征及肿瘤预后的相关性。利用GEO及Oncomine生物信息数据库验证LAMA3在胰腺癌组织中的表达情况。结果 免疫组化检测结果表明胰腺癌组织中的LAMA3蛋白高表达率比癌旁组织中显著升高（60.0% vs 25.0%,χ² =10.026,P＜0.05）。LAMA3蛋白表达与肿瘤大小、TNM分期显著相关（χ² =9.184,7.111,P＜0.05）,与性别、年龄、CA199、分化程度、淋巴结转移等因素无明显相关（P＞0.05）。生存分析表明LAMA3高表达提示预后不良（P＜0.05）。对GEO及Oncomine数据库分析显示,与正常癌旁组织相比LAMA3在胰腺癌组织中呈明显高表达（GSE16515,P＜0.0001;GSE15471,P＜0.0001;GSE3654,P＜0.0001）。结论 本研究表明LAMA3在胰腺癌组织中表达上调,其表达情况与患者的肿瘤大小、TNM分期显著相关,LAMA3可能是胰腺癌预后不良的预测因子。     

S100基因家族在胰腺癌早期诊断和预后方面的研究进展

肿瘤的发生发展受多种基因调控。近几年发现S100基因家族与胰腺癌关系密切,该家族基因编码一种钙离子结合调节蛋白,通过与钙离子结合在肿瘤发生发展中发挥重要作用。     

Identification and verification of ferroptosis-related genes in diabetic foot using bioinformatics analysis

Ferroptosis is a novel form of cell death that plays a key role in several diseases, including inflammation and tumours; however, the role of ferroptosis-related genes in diabetic foot remains unclear. Herein, diabetic foot-related genes were downloaded from the Gene Expression Omnibus and the ferroptosis database (FerrDb). The least absolute shrinkage and selection operator regression algorithm was used to construct a related risk model, and differentially expressed genes were analysed through immune infiltration. Finally, we identified relevant core genes through a protein–protein interaction network, subsequently verified using immunohistochemistry. Comprehensive analysis showed 198 genes that were differentially expressed during ferroptosis. Based on functional enrichment analysis, these genes were primarily involved in cell response, chemical stimulation, and autophagy. Using the CIBERSORT algorithm, we calculated the immune infiltration of 22 different types of immune cells in diabetic foot and normal tissues. The protein–protein interaction network identified the hub gene TP53, and according to immunohistochemistry, the expression of TP53 was high in diabetic foot tissues but low in normal tissues. Accordingly, we identified the ferroptosis-related gene TP53 in the diabetic foot, which may play a key role in the pathogenesis of diabetic foot and could be used as a potential biomarker.     

闭合性胰腺损伤的处理与预后因素分析

目的　探讨闭合性胰腺损伤的处理及影响预后的因素。方法　对我院 1993年 2月～ 2 0 0 3年 1月收治的 3 8例闭合性胰腺损伤病例的临床资料进行回顾性分析。结果　 3 8例中 ,术前确诊 17例 ( 4 4.7% ) ,3 5例治愈 ( 92 .1% ) ,3例死亡 ( 7.9% ) ;发生并发症 8例 ( 2 1.1% ) ,术后继发出血和胰漏是主要的并发症。结论　闭合性胰腺损伤术前诊断困难。根据术中探查情况采取简单而合理的手术方式是外科治疗的关键。正确的围手术期处理是影响胰腺损伤预后的主要因素。     

Histological prognostic parameters for adenocarcinoma of the pancreatic head. Proposal for a scoring system for prediction of outcome

To find new histopathological prognostic parameters for adenocarcinoma of the pancreatic head, 27 of these carcinomas, at stage IV according to the Japan Pancreas Society, which had been curatively resected, were histologically examined. In addition to previously recognized histological prognostic parameters, sections were examined for the following factors: fibrotic focus (FF), direct invasion of the tumor into the lymph node (DILN), and tumor necrosis (TN). Frequency of tumor recurrence or death was higher in patients with any one of the three new factors than in those without any of these factors. To develop an accurate system for predicting the outcome, the presence or absence of each factor and lymphatic permeation was given a score of 1 (present) or 0 (absent), and the total score was than calculated for each patient. All patients with a score of 0 were alive without tumor recurrence, at a mean follow-up of 20 months, whereas all seven patients with a score of 4 had experienced tumor recurrence, and six died subsequently. The results of this study demonstrated that FF, DILN, and TN are good histological parameters of ductal adenocarcinoma of the pancreatic head, and that the scoring system proposed in this paper is useful for prediction of the outcome of the disease.     

Preoperative prediction of complete resection in pancreatic cancer

BACKGROUND: Accurate preoperative staging is essential in pancreatic cancer to select the 15% of patients who can benefit from surgery and avoid surgery in the 85% with advanced disease. With improvements in computed tomography (CT) scanning, the value of routine laparoscopy for preoperative staging of pancreatic cancer has been questioned because it changes the preoperative plan in less than 20% of unselected cases. METHODS: We retrospectively reviewed our experience with preoperative staging in 88 consecutive patients with pancreatic cancer. All patients had preoperative CT scans, and selective criteria were used to determine which patients would also undergo preoperative staging laparoscopy. Patients were categorized preoperatively as resectable or not resectable (locally advanced or metastatic). Medical records, operative, and pathology reports were reviewed to determine the accuracy of preoperative predictions. RESULTS: Thirty patients were deemed resectable based on CT alone and 27 (90%) were resected (25 R0, 2 R1). Two (7%) had metastatic disease discovered at laparotomy and one (3%) had a R2 resection. Only 19 patients (39%) of 49 patients deemed resectable by CT met our selective criteria for preoperative staging laparoscopy. Laparoscopy changed the treatment plan in 11 (58%) of these patients. Eight were still deemed resectable after staging laparoscopy and 7 (88%) were resected (6 R0, 1 R1). One patient (12%) had metastatic disease diagnosed at laparotomy. If selective staging laparoscopy were eliminated from our algorithm, 49 patients would have been deemed potentially resectable based on CT alone, 34 (69%) would have been found to be resectable at laparotomy (31 R0, 3 R1), and 15 (31%) would have been found to be unresectable at laparotomy (positive predictive value of 69%). The addition of selective staging laparoscopy avoided unnecessary laparotomy in 11 patients and increased the positive predictive value to (34/38) 89%. CONCLUSION: Selective use of laparoscopy increases the positive predictive value of preoperative staging in pancreatic cancer and avoids unnecessary laparoscopy in the majority of patients.