The impact of PTEN deletion and ERG rearrangement on recurrence after treatment for prostate cancer: a systematic review and meta-analysis

Clinical and Translational Oncology - The specific association between PTEN deletion or ERG rearrangement and the recurrence of prostate cancer (PC) treated with radical prostatectomy (RP) or...     

Mutation status and burden can improve prognostic prediction of patients with lower‐risk myelodysplastic syndromes

Patients with lower‐risk myelodysplastic syndromes (LR‐MDS) as defined by the International Prognostic Scoring System (IPSS) have more favorable prognosis in general, but significant inter‐individual heterogeneity exists. In this study, we examined the molecular profile of 15 MDS‐relevant genes in 159 patients with LR‐MDS using next‐generation sequencing. In univariate COX regression, shorter overall survival (OS) was associated with mutation status of ASXL1 (P = .001), RUNX1 (P = .031), EZH2 (P = .049), TP53 (P = .016), SRSF2 (P = .046), JAK2 (P = .040), and IDH2 (P = .035). We also found significantly shorter OS in patients with an adjusted TET2 variant allele frequency (VAF) ≥18% versus those with either an adjusted TET2 VAF <18% or without TET2 mutations (median: 20.4 vs 47.8 months; P = .020; HR = 2.183, 95%CI: 1.129‐4.224). After adjustment for IPSS, shorter OS was associated with mutation status of ASXL1 (P < .001; HR = 4.306, 95% CI: 2.144‐8.650), TP53 (P = .004; HR = 4.863, 95% CI: 1.662‐14.230) and JAK2 (P = .002; HR = 5.466, 95%CI: 1.848‐16.169), as well as adjusted TET2 VAF ≥18% (P = .008; HR = 2.492, 95% CI: 1.273‐4.876). Also, OS was increasingly shorter as the number of mutational factors increased (P < .001). A novel prognostic scoring system incorporating the presence/absence of the four independent mutational factors into the IPSS further stratified LR‐MDS patients into three prognostically different groups (P < .001). The newly developed scoring system redefined 10.1% (16/159) of patients as a higher‐risk group, who could not be predicted by the currently prognostic models. In conclusion, integration of the IPSS with mutation status/burden of certain MDS‐relevant genes may improve the prognostication of patients with LR‐MDS and could help identify those with worse‐than‐expected prognosis for more aggressive treatment.     

丙戊酸钠通过EGFR下调CD44表达抑制胶质瘤细胞生长

目的:探讨丙戊酸钠通过抑制A172胶质瘤细胞表皮生长因子受体（epidermal growth factor receptor，EGFR）的活化，下调CD44表达，进而调节细胞生长的机制。方法:实时荧光定量PCR和Western blot检测A172胶质瘤细胞中CD44以及siRNA下调CD44表达的情况，MTT检测CD44和丙戊酸钠对细胞生长的影响，Western blot检测丙戊酸钠对细胞中p-EGFR、EGFR和CD44表达影响。结果:丙戊酸钠抑制A172胶质瘤细胞生长，并具有浓度依赖性。A172胶质瘤细胞表达CD44，siRNA下调CD44表达后，细胞生长较正常组显著减缓。活化EGFR促进A172胶质瘤CD44蛋白表达，而EGFR的抑制剂Lapatinib可显著抑制上述效应。丙戊酸钠抑制EGFR磷酸化，下调CD44蛋白表达。结论:丙戊酸钠抑制A172胶质瘤细胞的生长。抑制A172胶质瘤细胞中EGFR的活化，下调CD44的表达，是丙戊酸钠抑制胶质瘤细胞生长的其中一个机制。     

局部晚期食管鳞癌新辅助放疗剂量与病理完全缓解关系分析

目的 探讨接受新辅助放化疗的局部晚期食管鳞癌患者新辅助放疗剂量与病理完全缓解(pCR)的关系。方法 收集2017-2019年间在四川大学华西医院肿瘤中心经病理确诊为食管鳞癌并接受新辅助放化疗和手术的 116例局部晚期患者临床资料。116例患者中 40~45Gy组 80例,≥45Gy组 36例,分析两组术后pCR率。结果 全组患者的pCR率为38.8%(45/116),40~45Gy组与≥45Gy组的pCR率分别为44%(35/80)和28%(10/36)(P=0.105)。结论 术前新辅助采用较高的放疗剂量不增加局部晚期食管鳞癌的pCR率,有必要进行前瞻性的临床研究确定合适的新辅助放疗剂量。     

Germline variant burden in multidrug resistance transporters is a therapy-specific predictor of survival in breast cancer patients

Multidrug resistance due to facilitated drug efflux mediated by ATP-binding cassette (ABC) transporters is a main cause for failure of cancer therapy. Genetic polymorphisms in ABC genes affect the disposition of chemotherapeutics and constitute important biomarkers for therapeutic response and toxicity. Here we correlated germline variability in ABC transporters with disease-specific survival (DSS) in 960 breast cancer (BRCA), 314 clear cell renal cell carcinoma and 325 hepatocellular carcinoma patients. We find that variant burden in ABCC1 is a strong predictor of DSS in BRCA patients, whereas candidate polymorphisms are not associated with DSS. This association is highly drug-specific for subgroups treated with the MRP1 substrates cyclophosphamide (log-rank p = 0.0011) and doxorubicin (log-rank p = 0.0088) independent of age and tumor stage, whereas no association was found in individuals treated with tamoxifen (log-rank p = 0.13). Structural mapping of significant variants revealed multiple variants at residues involved in protein stability, cofactor stabilization or substrate binding. Our results demonstrate that BRCA patients with high variant burden in ABCC1 are less prone to respond appropriately to pharmacological therapy with MRP1 substrates, thus incentivizing the consideration of genomic germline data for precision cancer medicine.     

食管鳞癌患者远处转移部位与预后的相关性及生存分析

目的:探讨食管鳞癌患者远处转移部位与预后的相关性及生存分析。方法:从SEER数据库中提取2010年至2015年共439例食管鳞癌伴远处转移患者的临床资料，回顾性分析比较食管鳞癌远处转移部位与预后的相关性，通过χ2检验比较两组变量的差异，采用Kaplan-Meier法绘制生存曲线，Log-rank检验进行单因素分析，COX回归进行多因素分析。结果:肺转移、骨+肺转移、肝+肺转移患者预后较好；骨转移、脑转移、骨+脑转移、骨+脑+肝+肺转移患者预后较差。单因素分析显示:年龄、原发灶部位、T分期、手术情况、多器官转移情况与食管鳞癌远处转移患者的预后有关（P＜0.05）；多因素分析显示:年龄、手术情况与多器官转移情况是影响食管鳞癌远处转移患者总生存时间（OS）的独立危险因素。结论:食管鳞癌伴远处转移的患者整体预后较差，但年龄在60~69岁区间、接受手术治疗与较好的预后相关。仅单器官转移的食管鳞癌患者中，骨转移、脑转移患者预后较差；合并多器官转移的患者中，骨+脑转移、骨+脑+肝+肺转移患者预后较差。     

基于Andersen行为模型的消化道肿瘤患者支持性照顾需求现状及影响因素分析

目的调查消化道肿瘤患者的支持性照顾需求现状并分析其影响因素。方法于2019年1—10月间,采用便利抽样的方法,抽取重庆市三峡中心医院内消化道肿瘤患者共370例,采用一般资料调查表、癌症病人支持性照顾需求简明问卷(SCNS-SF34)、医院焦虑和抑郁量表(HADS)、社会网络支持量表(LSNS)进行问卷调查。以Andersen行为模型为基础,将调查内容中关于消化道肿瘤患者支持性照顾需求的影响因素分别纳入倾向性因素、使能因素和需求性因素中,构建4个线性回归模型进行分析,并检验各模型的拟合优度,采用多元线性回归分析消化道肿瘤患者支持性照顾需求的影响因素。结果共发放问卷370份,回收有效问卷365份,有效回收率为98.6%。365例消化道肿瘤患者支持性照顾需求总均分为(3.42±0.54)分,其中生理与日常生活需求>健康信息需求>照顾与支持需求>心理需求>性需求。多元线性回归分析结果显示:倾向性因素中年龄、婚姻状况,使能因素中的家庭平均月收入、疾病负担能力、社会网络支持,需求性因素中的病程、疾病分期、疼痛情况、焦虑程度、抑郁程度是消化道肿瘤患者支持性照顾需求的主要影响因素(P<0.05)。结论消化道肿瘤患者有较高的支持性照顾需求,其需求受多种因素的影响,建议临床医护人员针对不同需求患者进行针对性满足,并对不同影响因素进行综合考量并加以分类分析。