PALB2 as a potential prognostic biomarker for colorectal cancer

Partner and localizer of BRCA2 (PALB2) is regarded as a colorectal cancer (CRC) risk gene, but the prognostic implication of PALB2 in CRC remains unclear. In this study, we evaluate the prognostic value of the gene copy number alteration (CNA) and mRNA expression of PALB2 in The Cancer Genome Atlas (TCGA) database, and then validated with our database. We downloaded the copy number and mRNA data of PALB2 from TCGA database and examined the relationship among the genetic alterations, expression levels and survival outcomes. Gene ontology (GO) analysis was performed to study the function of PALB2. cBioPortal database was used to explore the potential co-expression genes of PALB2. There were 6.3% (37 of 582) CRC patients diagnosed as PALB2 gene deletion. The PALB2 deletion group expressed significantly lower of PALB2 mRNA than the non-deletion group (P < 0.001). Survival analysis showed that PALB2 deletion was significantly associated with shorter disease-free survival (DFS) (P = 0.026) and overall survival (OS) (P = 0.028). Low mRNA expression of PALB2 correlated with shorter OS (P < 0.001). Multivariate analysis also confirmed that PALB2 deletion and low mRNA expression of PALB2 were independent prognostic factors of poor OS in CRC (P = 0.019, 0.034, respectively). In validation cohort, negative expression of PALB2 was associated with shorter OS (P = 0.006) in stage I patients. Multivariate analysis confirmed that negative expression of PALB2 was a poor-prognostic factor (P = 0.002). GO analysis and co-expression analysis investigated that PALB2 is primarily involved in the DNA repair process. These results suggest that PALB2 gene copy number deletion and low mRNA expression could be novel prognostic biomarkers for CRC.     

Gastric cancer in proximal site exerts poorer survival outcome with divergent genetic features than distal site

BackgroundAnatomical subsites always harbor specific biological features in carcinogenesis. The divergent prognosis of proximal gastric cancer (PGC) and distal gastric cancer (DGC) has been reported. The current study aimed to comprehensively interpret anatomic subsite-specific genomic profiles, which may improve the effectiveness of personalized management.MethodsSurvival and genomic data from the online Surveillance, Epidemiology, and End Results (SEER) and The Cancer Genome Atlas (TCGA) databases were queried for prognostic and genetic analysis, respectively. Propensity score matching (PSM) analysis was performed to balance patient epidemiological factors. Differentially expressed genes (DEGs) were analyzed using the DESeq algorithm. Functional enrichment was performed by the clusterProfiler package. The protein-protein interaction network of DEGs was predicted by the online STRING database.ResultsA total of 3,955 patient pairs were assembled by PSM in SEER data with even background characteristics. Prognostic analysis indicated worse overall survival of PGC than DGC (17 vs 20 months, p = 0.0002). Genetic analysis of TCGA database identified 280 DEGs, 90 of which were upregulated in the DGC group and the remaining 190 were upregulated in the PGC group. Functional enrichment analysis indicated that kallikrein serine protease activity, ion channel (Na⁺/Cl⁻) activity, and cytoskeleton constituent might be attributed to the poor prognosis observed in PGC. Furthermore, alcohol, retinol, and lipoprotein metabolism were the features for DGC malignancy.ConclusionThe current study first demonstrated that PGC exerts poorer survival outcome than DGC based on the SEER database. Further bioinformatic investigation depicts the specific genetic features for PGC and DGC, which may generate differences in tumor malignancy. Our findings provide promising genetic targets for future specific and individualized gastric cancer therapy.     

Applications of computational homology to the analysis of treatment response in breast cancer patients

The experimental method comparative genomic hybridization (CGH) array provides a full picture of chromosome amplifications and deletions of an individual's genome. The multi-dimensional nature of these data, however, has not been fully explored. Current methods for CGH analysis focus on specific markers, but deeper understanding can be gained by examining the properties of the overall genomic profile. In this paper we propose a novel method for characterizing CGH profiles mathematically using algebraic homology. We apply our method to breast cancer CGH profiles from patients that have been subjected to different treatments. We show that our results obtained using homology are in agreement with previous studies and are able to distinguish between frequency of cancer recurrence in chemotherapy and non-treated patient populations.     

老年抑郁症患者预后相关因素研究

目的探讨影响老年抑郁症患者预后的相关因素。方法收集住院或门诊就诊的87例老年抑郁症患者的一般资料,并进行生活事件量表（LES）、艾森克人格问卷（EPQ）、简易智力状态检查表（MMSE）和社会支持评定量表（SSRS）等因子评定,采用大体功能评定量表（GAS）评定老年抑郁症患者的预后疗效,并根据GAS分值分组,GAS≤60分视为预后差,作为研究组;GAS＞60分视为预后好,作为对照组。通过logistic回归分析,探讨影响老年抑郁症患者预后的相关因素。结果87例老年抑郁症患者中疗效差者占37.9%。两组患者在起病形式、治疗是否恰当、治疗依从性、合并慢性躯体疾病、负性生活事件值、对社会支持的利用度、EPQ的N维度分值及MMSE总分等因子方面的差异均有统计学意义（均P＜0.05）,经多元logistic回归分析发现,影响老年抑郁症预后的主要因素为：治疗依从性、慢性躯体疾病、EPQ标准N维度分值、合并精神病症状及对支持的利用度。结论老年抑郁症患者的预后可能受精神病理学、神经心理学和家庭社会等多种因素的影响,应从多方位着手,降低复发率,提高生活质量。     

多形性脑胶质母细胞瘤中1p/19q杂合性缺失的表达及其意义

目的探讨多形性胶质母细胞瘤（GBM）中1p/19q杂合性缺失（1p/19q LOH）的表达类型及其意义。方法通过荧光原位杂交法检测29例GBM、17例间变性星形细胞瘤（AA）和12例少突星形细胞瘤（OA）中1p/19q LOH的表达及其差异。结果 GBM、AA和OA中1p/19q LOH的发生率分别为24.1%、35.3%和75.0%，其中同时发生1p和19q LOH的比率分别为13.8%、23.5%和66.7%，GBM中1p/19q LOH的发生率明显低于AA和OA（P＜0.05）。GBM的VEGF阳性表达率和Ki-67增殖指数分别为75.9%和87.66±16.21，AA为47.1%和49.57±4.73，OA为41.7%和41.62±4.25，GBM与后两者比较，均有统计学差异（均P＜0.05）。1p/19q LOH的发生率与VEGF阳性表达和Ki-67增殖指数呈负相关（均P＜0.05）。结论1p/19q LOH的表达可能有助于评估GBM患者对烷化剂类药物治疗的敏感性及其预后。     

系统性疾病相关ILD 患者血清CEA 水平与疾病严重程度及预后的相关性

目的 研究血清癌胚抗原（CEA）在系统性疾病相关的间质性肺病（ILD）患者中的表达情况,及其与疾病严重程度及 预后的相关性。方法 收集80 例系统性疾病相关ILD 患者,并设立对照组,统计血清CEA 水平,并将血清CEA 水平与疾病严重程度指标进行Pearson相关分析,最后采用Kaplan-Meier生存分析及Cox 回归分析评估血清CEA 水平对1 年生存率的影响。结果 病例组血清CEA 水平明显升高,血清CEA 水平与ILD 严重程度指标均相关,并与1年生存率显著相关（均P＜0.05）。结论 血清CEA 水平是评估系统性疾病相关ILD 病情及预后有较好相关性的血清学指标。     

胃癌组织中B7-H1的表达及临床意义研究

目的检测人体胃癌组织中B7-H1的表达,探讨其与患者临床病理特征的关系及对预后的影响。方法采用免疫组化染色法检测胃癌组织中B7-H1的表达,分析其在胃癌组织中的阳性表达率与患者临床病理特征之间的关系,并绘制患者术后生存曲线,评价B7-H1表达对预后的影响。结果65例胃癌组织中癌细胞的细胞膜、细胞质以及部分肿瘤组织浸润的淋巴管及淋巴细胞中均有检测到B7-H1的阳性表达,阳性率为36.9%。有淋巴结转移或脉管内有癌栓的患者B7-H1阳性率较高（均P＜0.05）。B7-H1阳性表达的胃癌患者术后5年生存率（25.0%）低于阴性表达的患者（56.1%）（P＜0.05）。结论B7-H1阳性表达的胃癌患者易发生淋巴结转移,预后较差,B7-H1可作为评价胃癌患者预后的指标之一。     

A two-stage prognosis model in condition based maintenance

We often observe in practice that the life of a piece of production equipment can be divided into two stages. The first stage is referred to as the normal working stage where no significant deviation from the normal operating state is observed. The second stage is called the failure delay period, since a defect may be initiated, and progressively develop into an actual failure, i.e., the equipment is in a defective stage but still working during this stage. With the help of condition monitoring, hidden defects already present in the equipment may be detected, but for maintenance planning purposes, the prediction of the initiation point of the second stage, and more importantly, the residual life thereafter is important. This paper reports on the development of a probability model to predict the initiation point of the second stage and the remaining life based on available condition monitoring information. The method for model parameters estimation is discussed and applied to real data.     

肿瘤干细胞标志CD166在结肠癌中的表达及其临床生物学意义

目的探讨肿瘤干细胞标志CD166在原发结肠癌组织中的表达及其临床生物学意义。方法收集57例患者的原位结肠癌组织,应用免疫组织化学检测其CD166表达。应用流式细胞分选（FACS）技术,以CD166/CD133标志分选结肠癌细胞株SW620,通过NOD/SCID小鼠脾脏移植,观察肝转移情况。结果 CD166可表达于结肠癌细胞的细胞质和细胞膜,其中细胞质阳性率98.2%（56/57）,细胞膜阳性率42.1%（24/57）。膜CD166阳性表达与局部浸润（P=0.010）、pTNM分期（P=0.035）、远处转移（P=0.013）、年龄（P=0.026）相关;而与性别（P=0.426）、淋巴结转移（P=0.104）、肿瘤分化（P=0.171）无相关性。Log-rank生存分析显示：结肠癌细胞膜CD166阳性表达与患者生存期（P=0.014）呈负相关。动物实验的初步结果显示：脾包膜接种CD166阳性的SW620细胞可形成肝转移灶。结论 CD166阳性表达与肿瘤局部进展和远处转移有关,是判断预后不良的标志,CD166阳性的肿瘤细胞可能具有肝转移潜能。     

淋巴细胞计数对弥漫大B细胞淋巴瘤的预后价值分析

目的探讨外周血淋巴细胞绝对数(ALC)与初发弥漫大B细胞淋巴瘤(DLBCL)患者预后的关系.方法回顾性分析71例DLBCL患者的临床特征,比较初发时ALC不同的患者之间临床特点及转归.结果71例患者中,ALC>1×109/L者27例(38.0%),ALC≤1×109/L者44例(62.0%).ALC不同的两组患者间,年龄、性别、临床分期、B症状等临床特征均无统计学差异(均P>0.05).ALC低者Hb平均值更低,淋巴细胞亚群中T辅助细胞、NK细胞百分比更低,总T细胞、T抑制细胞百分比更高(均P<0.05).共同接受CHOP方案治疗条件下,初诊时ALC低者临床缓解率相对较低,病死率较高,中位生存期更短,总生存率更低(均P<0.05).结论 ALC减少可能成为DLBCL患者预后的重要指标.