A rare case of metastatic pancreatic adenocarcinoma presenting as a pulmonary embolism from nonbacterial thrombotic endocarditis

Nonbacterial thrombotic endocarditis (NBTE) also called, "Marantic endocarditis" occurs due to an underlying hypercoagulable state causing tissue damage and upregulation of the coagulation cascade, with noninfective vegetation formation on heart valves. Mitral and aortic valves are most commonly involved. NBTE is rare, with an incidence of 1.6%, with 65 cases identified during a 10-year autopsy analysis. The most common malignancies associated with NBTE include gynecological cancers, lung cancer, gastric cancer, and pancreatic cancers with adenocarcinoma histology being the greatest risk. Herein, we present a rare case of a 55-year-old male who presented with acute hypoxic respiratory failure secondary to pulmonary embolism due to nonbacterial thrombotic endocarditis. He was found to have advanced pancreatic adenocarcinoma on further investigation of the 2.2 cm hypodense cystic mass in the distal pancreatic body and tail, and complex liver masses which were incidentally found on computed tomography angiography (CTA) of the chest. This is a rare phenomenon and clinicians have to consider the hypercoagulable state associated with cancers, particularly pancreatic adenocarcinoma, and the risk of NBTE.     

基于TCGA数据库应用生物信息学方法分析和挖掘肺腺癌预后和诊断miRNA研究

目的基于TCGA数据库,应用生物信息学方法分析和挖掘肺腺癌预后和诊断miRNA生物学标志物。方法数据下载:从TCGA下载获取肺腺癌miRNA表达谱数据,包括miRNAseq和临床数据。筛选差异表达miRNAs:应用R-version 3.6.2软件中的edgeR包筛选肺腺癌组织和正常肺组织的差异基因,以│logFC│>2,P<0.05为筛选条件。筛选与预后相关miRNAs:应用R-version 3.6.2软件中的survival包绘制KM生存曲线,筛选与预后相关的miRNAs。筛选可作为肺腺癌诊断的miRNAs:应用R-version 3.6.2软件中的pROC包制作受试者工作特征曲线(ROC)评价与预后相关miRNAs诊断肺腺癌的特异性和敏感性。结果共识别到肺腺癌与正常肺组织差异表达的miRNA 144个,其中上调表达119个,下调表达25个。通过K-M生存曲线筛选出与预后显著相关(P<0.05)的miRNA共13个,分别为hsa-miR-139-3p、hsa-miR-328-3p、hsa-let-7g-3p、hsa-miR-142-3p、hsa-miR-147b...     

Differential expression and analysis of extrachromosomal circular DNAs as serum biomarkers in lung adenocarcinoma

BackgroundExtrachromosomal circular DNAs (eccDNAs) increase the number of proto‐oncogenes by enhancing oncogene expression to promote tumorigenesis. However, there are limited reports on differential eccDNA expression and analysis in lung cancer, especially in lung adenocarcinoma (LAD).MethodsThree LAD and three corresponding NT tissues samples were used for eccDNA next‐generation sequencing analysis, and an additional 20 were used for quantitative PCR (qPCR) evaluations. We further performed qPCR amplification using serum samples from LAD patients and healthy medical examiners.ResultseccDNAs from LAD samples were mainly 200–1000 bp in length. Gene annotation analysis revealed that most eccDNAs were derived from chromosomes 1 and 2. The top‐ten increased and top‐ten decreased eccDNAs in LAD tissues were CircD‐ARPC1B, CircD‐ARPC1A, CircD‐FAM49B, CircD‐SDK1, CircD‐KCNG1, CircD‐POLR2F, CircD‐SS18L1, CircD‐SLC16A3, CircD‐CSNK1D, CircD‐KCTD1, and CircD‐TMIGD2, CircD‐PDIA5, CircD‐VAV2, CircD‐GATAD2A, CircD‐CAB39L, CircD‐KHDC1, CircD‐FOXN3, CircD‐SULT2B1, CircD‐DPP9, and CircD‐CSNK1D. qPCR demonstrated that the expression of CircD‐DZRN3 was higher in LAD tissues than in normal lung tissues, whereas CircD‐LGR6 and CircD‐UMODL1 expression levels were lower in LAD than in normal lung tissues. Furthermore, the serum CircD‐PDZRN3 level increased, while CircD‐LGR6 decreased in LAD. Receiver operating characteristic (ROC) analysis showed that area under curve (AUC) of serum CircD‐PDZRN3 (0.991), CircD‐LGR6 (0.916) was higher than that of serum carcinoembryonic antigen (CEA) (0.825), CY211 (cytokeratin 19 fragment) (0.842), SCCA(squamous cell carcinoma antigen) (0.857) for the diagnosis of LAD.ConclusionsOur study first showed that several eccDNAs were aberrantly expressed in LAD, among which CircD‐PDZRN3 and CircD‐LGR6 clearly distinguished LAD patients from healthy controls, indicating their potential as biomarkers.     

Significant accumulation of KRAS mutations in bronchiolar metaplasia-associated honeycomb lesions of interstitial pneumonia

Interstitial pneumonia (IP) is a major risk factor for lung adenocarcinoma (LADC). IP-related LADC predominantly develops in the bronchiolar metaplasia lining in honeycomb lesions. Kirsten rat sarcoma virus (KRAS) is the most common oncogene mutated in IP-related LADC. The present study examined the metaplastic epithelia in honeycomb lesions for KRAS mutations using digital droplet polymerase chain reaction (ddPCR), a sensitive method used to detect infrequent mutations. Significantly higher KRAS mutation variant allele frequencies (VAFs) were detected in the metaplastic lung epithelia from 13 patients with IP compared with those in 46 non-lesioned lung samples from patients without IP (G12V, P=0.0004, G12C, P=0.0181, and G12A, P=0.0234; Mann Whitney U test). Multivariate analyses revealed that higher KRAS G12V (logistic regression model; P=0.0133, odds ratio=7.11) and G12C (P=0.0191, odds ratio=5.81) VAFs in patients with IP were independent of confounding variables, such as smoking and age. In patients with IP, metaplastic epithelia exhibited significantly higher KRAS G12V and G12C VAFs compared with the non-lesioned counterparts (paired t-test; G12V, P=0.0158, G12C, P=0.0465). These results suggested that IP could increase KRAS mutations and supported the hypothesis that bronchiolar metaplasia could be a precursor for IP-related LADC.     

Development of a novel five-gene immune-related risk model for the prognosis evaluation of prostate adenocarcinoma patients

The interaction between the immune cells and the host immune system with the tumor cells is significantly associated with the initiation and progression of prostate adenocarcinoma (PRAD), whereas the application of immune-related genes (IRGs) for the prognosis evaluation of PRAD patients is still lacking. In this study, we aimed to identify IRGs with prognostic values and to develop a clinically effective risk model. Wilcoxon rank-sum test and univariate Cox analysis were applied to identify the differentially expressed immune-related genes (DEIRGs) related to the survival of PRAD patients. The Least absolute shrinkage and selection operator (LASSO) analysis was performed to identify the independent prognostic DEIRGs and to establish an immune risk score prognostic model. The reliability and veracity of the prognostic model were validated in PRAD patients from the internal cohort (The Cancer Genome Atlas, TCGA dataset) and the external cohort (International Cancer Genome Consortium, ICGC dataset), respectively. Six of the 193 identified DEIRGs were survival-associated in PRAD patients. Five prognostic DEIRGs (SLPI, NOX1, DES, BIRC5 and AMH) were selected to construct the immune-related prognostic model with optimal robustness. In the 2 independent cohorts we chose, PRAD patients could be effectively stratified according to our risk model. Patients with high risk scores had worse survival. Clinical correlation analysis proved that the risk score was associated with advanced clinicopathologic features. Multivariate analysis indicated that the risk model was an independent prognostic indicator. We also established a nomogram based on the risk score model for clinical application. Additionally, the risk score model was correlated with immune cell infiltration and reflected the status of the immune microenvironment. The prognostic value of the five immune-related genes used in the prognostic model was also validated. Our immune-related prognostic model was an effective tool that could not only serve as a predictor for prognosis, but also provide potential prognostic and therapeutic molecular biomarkers for optimizing personalized therapies in clinical practice.     

一线培美曲塞联合艾迪注射液治疗老年晚期肺腺癌的临床观察

目的比较一线培美曲塞和培美曲塞联合艾迪注射液治疗老年晚期肺腺癌患者的疗效和不良反应。方法老年晚期肺腺癌患者共61例,随机分为治疗组和对照组。治疗组31例,培美曲塞500mg/m2,第1天静脉滴注,每3～4周为1个周期;艾迪50ml,静脉滴注,共15d;对照组30例,单药培美曲塞500mg/m2,第1天静脉滴注,3～4周为1个疗程。结果治疗组和对照组有效率(RR)分别为45.2%、43.3%,肿瘤控制率(TGCR)分别为71.0%、66.7%。两组不良反应均可耐受,治疗组耐受性及生存质量均高于对照组(P<0.05)。结论老年晚期肺腺癌患者可从单药一线培美曲塞中获益;培美曲塞联合艾迪注射液可减轻化疗相关不良反应,改善患者的生存质量。     

Comparative genomic analysis of esophageal squamous cell carcinoma and adenocarcinoma: New opportunities towards molecularly targeted therapy

Esophageal cancer is one of the most lethal cancers worldwide because of its rapid progression and poor prognosis. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are two major subtypes of esophageal cancer. ESCC predominantly affects African and Asian populations, which is closely related to chronic smoking and alcohol consumption. EAC typically arises in Barrett's esophagus with a predilection for Western countries. While surgical operation and chemoradiotherapy have been applied to combat this deadly cancer, molecularly targeted therapy is still at the early stages. With the development of large-scale next-generation sequencing, various genomic alterations in ESCC and EAC have been revealed and their potential roles in the initiation and progression of esophageal cancer have been studied. Potential therapeutic targets have been identified and novel approaches have been developed to combat esophageal cancer. In this review, we comprehensively analyze the genomic alterations in EAC and ESCC and summarize the potential role of the genetic alterations in the development of esophageal cancer. Progresses in the therapeutics based on the different tissue types and molecular signatures have also been reviewed and discussed.     

瘤内与瘤周CT影像组学模型结合临床及常规CT特征鉴别肺原位腺癌与微浸润性腺癌

目的 观察基于平扫CT瘤内及瘤周影像组学模型联合临床及常规CT特征鉴别肺原位腺癌(AIS)与微浸润性腺癌(MIA)的价值。方法 回顾性分析180例孤立性AIS及180例孤立性MIA肺结节患者,随机将其中各160例纳入训练集(n=320)、各20例纳入测试集(n=40)。以训练集AIS与MIA间差异有统计学意义的临床及常规CT特征构建临床模型;勾画瘤内(CTi)及包含瘤周2 mm(CTi+p2mm)、4 mm(CTi+p4mm)ROI,提取并筛选其影像组学特征,分别以之构建CTi模型、CTi+p2mm模型及CTi+p4mm模型;绘制受试者工作特征(ROC)曲线,计算曲线下面积(AUC),评价各模型效能,遴选预测测试集MIA效能最佳者,联合临床及常规CT特征构建联合模型,观察临床模型、最佳影像组学模型及联合模型的AUC、校准度及净收益。结果 训练集内,相比AIS,MIA结节直径较大、密度不均匀、伴血管穿行结节占比较高(P均＜0.05)。CTi+p2mm模型鉴别测试集MIA与AIS效能最高(AUC=0.838,P＜0.05);以之结合临床及常规CT特征构建的联合模型鉴别诊断效能更佳(AUC=0.867,P＜0.05)。联合模型的校准度及0.60~0.90阈值概率区间的临床净收益较高。结论 基于平扫CT构建的瘤内和瘤周2 mm ROI影像组学模型能有效鉴别肺MIA与AIS,联合临床及常规CT特征可进一步提高模型鉴别效能。     

磨玻璃结节样肺腺癌MSCT征象与Ki67、PKM2、SPINK1蛋白表达的相关性研究

目的:探讨磨玻璃结节(GGO)样肺腺癌的MSCT征象与Ki67、蛋白酪氨酸磷酸酶PKM2蛋白及丝氨酸蛋白酶抑制剂Kazal 1型(SPINK1)表达间的相关性.方法:选择手术治疗的80例肺腺癌患者作为研究对象,对患者进行胸部MSCT扫描,测量并记录结节大小、实性部分最大径、类型、个数、形态、边缘及内部结构特征;采用免疫...     

可变剪切事件在胰腺癌中的发生及其临床意义

目的探索胰腺癌(PAAD)中存在的差异RNA剪接模式,分析可变剪切(AS)事件与胰腺癌临床预后的关系。方法自癌症基因组图谱(TCGA)中下载RNA-seq数据、临床数据资料,提取剪接因子(SF)表达量;采用TCGA SpliceSeq工具下载提取AS事件数据,评估7种可变剪切类型在胰腺癌病例中的发生情况;采用Kaplan-Meier分析及Cox回归分析评估AS事件风险值和生存时间之间的相关性,并探索PAAD的独立危险因素;采用Cytoscape构建基于生存相关的AS事件与SF的调控关系网络。结果PAAD中与生存相关的AS事件以外显子跳跃(ES)类型多见,外显子互斥(ME)类型较少;各亚型AS事件对生存影响不同,低风险组的预后较好,且风险值可作为PAAD独立预后因素(P<0.01,AUC=0.765)。剪接网络提示PAAD患者中剪接因子的表达与AS事件之间具有相关性。结论AS事件风险值可作为PAAD的独立预后因子,且SF对AS事件的调控呈多样性,SF可能会作为PAAD治疗的潜在靶点。