基于生物信息学筛选早发性乳腺癌差异表达基因

目的筛选并分析与早发性乳腺癌发生、发展相关的靶基因。 方法(1)在美国国立生物技术信息中心的公共基因芯片数据库(GEO)中检索早发性乳腺癌样本及非早发性乳腺癌样本相关基因芯片数据。对上述数据使用GEO2R、R4.1.2及Venn软件筛选出相关差异表达基因(DEGs)，并运用在线分析工具(Web Gestalt)对DEGs，进行相关功能和信号通路富集分析。(2)同时，通过String在线数据库构建DEGs编码的蛋白质-蛋白质相互作用(PPI)网络，并利用Cytohubba插件对该网络中的基因进行评分，筛选出枢纽基因。将枢纽基因导入Kaplan-Meier生存分析工具(Kaplan-Meier Plotter)，评估枢纽基因在早发性乳腺癌的预后价值。(3)将肿瘤基因组图谱(TCGA)数据库中的肿瘤组织以年龄为标准进行分组，分析枢纽基因在各年龄组中的表达，并与正常组织中的表达进行比较，对得到的枢纽基因进行验证。DEGs表达量的多组间比较使用Kruskal-Wallis H检验，使用Bonferroni法进行两两比较。 结果(1)筛选出编号为GSE89116、GSE109169、GSE36295的基因芯片数据集，共得到80个差异表达基因，其中上调差异表达基因17个，下调差异表达基因63个。富集分析显示：DEGs主要富集在脂质代谢和氧化还原过程以及PPAR信号通路、AMPK信号通路上。(2)在PPI中发现主要的关键基因为PPARG、ADIPOQ、LIPE、PCK1、PDK4、ACACB、PLIN1、CAV1、CD36、ANGPTL4。ACACB、ADIPOQ、CAV1、LIPE、PLIN1、PPARG基因的低表达与乳腺癌患者的不良OS相关(HR＝0.69、0.84、0.76、0.88、0.78、0.82；95%CI：0.59~0.80、0.76~0.93、0.67~0.83、0.79~0.97、0.70~0.86、0.73~0.90；P均<0.050)。(3)ACACB、ADIPOQ、LIPE、PLIN1、CAV1及PPARG这6个与预后相关的基因在正常组织中的表达量均远高于各年龄组肿瘤组织中的表达量(χ²＝104.03、179.57、161.85、189.87、118.56、103.62，P均<0.001)，早发性乳腺癌组(21~40岁)的LIPE、PLIN1表达量低于41~60岁、61~80岁年龄组，差异具有统计学意义(LIPE: Z＝21.07、23.12, P均<0.050; PLIN1：Z＝16.89、18.76, P均<0.050)。 结论早发性乳腺癌与非早发性乳腺癌存在差异基因表达谱，LIPE、PLIN1可能是早发性乳腺癌发生、发展的关键基因。     

Association of kidney function with cancer incidence and its influence on cancer risk of smoking: The Japan Multi-Institutional Collaborative Cohort Study

The association between kidney function and cancer incidence is inconsistent among previous reports, and data on the Japanese population are lacking. It is unknown whether kidney function modifies the cancer risk of other factors. We aimed to evaluate the association of estimated glomerular filtration rate (eGFR) with cancer incidence and mortality in 55 242 participants (median age, 57 years; 55% women) from the Japan Multi-Institutional Collaborative Cohort Study. We also investigated differences in cancer risk factors between individuals with and without kidney dysfunction. During a median 9.3-year follow-up period, 4278 (7.7%) subjects developed cancer. Moderately low and high eGFRs were associated with higher cancer incidence; compared with eGFR of 60-74 ml/min/1.73 m², the adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for eGFRs of ≥90, 75-89, 45-59, 30-44 and 10-29 ml/min/1.73 m² were 1.18 (1.07-1.29), 1.09 (1.01-1.17), 0.93 (0.83-1.04), 1.36 (1.00-1.84) and 1.12 (0.55-2.26), respectively. High eGFR was associated with higher cancer mortality, while low eGFR was not; the adjusted subdistribution HRs (95% CIs) for eGFRs of ≥90 and 75-89 ml/min/1.73 m² were 1.58 (1.29-1.94) and 1.27 (1.08-1.50), respectively. Subgroup analyses of participants with eGFRs ≥60 and <60 ml/min/1.73 m² revealed elevated cancer risks of smoking and family history of cancer in those with eGFR <60 ml/min/1.73 m², with significant interactions. Our findings suggest that the relationship between eGFR and cancer incidence was U-shaped. Only high eGFR was associated with cancer mortality. Kidney dysfunction enhanced cancer risk from smoking.     

Pulmonary metastases in urogenital cancers: Surgical treatment and outcomes

IntroductionMetastasis is remaining one of the major problems in cancer treatment. Like many other malignancies, urogenital tumors originating from kidney, prostate, testes, and bladder tend to metastasize to the lungs.The aim of this retrospective study is to evaluate the operative results and prognosis of pulmonary metastasectomy in patients with primary urogenital tumors.MethodsThis study was approved by the local ethical committee. We retrospectively analyzed the surgical and oncological results of patients who underwent lung resections for urogenital cancer metastases in our department between 2002 and 2018. Demographic data and clinicopathological features were extracted from the medical records. Survival outcomes according to cancer subtypes and early postoperative results of VATS and thoracotomy were analyzed.Results22 out of 126 patients referred for pulmonary metastasectomy to our department had metastases from urogenital tumors. These patients consisted of 17 males and five females. Their metastasis originated from renal cell carcinoma (RCC; n = 9), bladder tumor (n = 7), testis tumors (n = 4), and prostate cancer (n = 2). There was no intraoperative complication. Postoperative complications were seen in 2 patients.ConclusionsAlthough pulmonary metastasectomy in various types of tumors is well known and documented, the data is limited for metastases of urogenital cancers in the literature. Despite the limitations of this study, we aim to document our promising results of pulmonary metastasectomy in patients with primary urogenital tumors and wanted to emphasize the role of minimally invasive approaches.     

p53基因突变与骨髓增殖性肿瘤临床特征及预后关系

探究p53 基因突变与骨髓增殖性肿瘤（MPN）临床特征及预后的关系。方法 选取2017年1月～2020年1月本院收治的MPN患者126例，二代测序法检测患者p53 基因突变情况。对患者进行随访，统计患者总生存（OS）时间和累计生存率；分析p53 基因突变对患者临床特征、预后的影响。结果 126例MPN患者中12例（9.52%）检出p53基因突变，突变主要位于4~8号外显子上，不同类型患者的p53 基因突变检出率比较差异无统计学意义（P＞0.05）。p53突变组患者年龄大于p53 非突变组，WBC水平低于p53 非突变组（P＜0.05），两组患者的染色体核型、IPSS预后分层比较差异无统计学意义（P＞0.05）；p53 非突变组患者的OS时间、累计生存率均明显高于p53突变组患者（P＜0.05）。结论 MPN患者p53 基因突变发生率较高，与患者年龄、WBC水平、异常核型及IPSS预后分层相关，p53 基因突变会影响患者的预后，可作为临床筛查预后不良高风险人群的客观指标。     

全腹腔镜、腹腔镜辅助与开腹胃癌根治术治疗Ⅱ、Ⅲ期胃癌的疗效对比

目的探讨全腹腔镜胃癌根治术（TLG）、腹腔镜辅助胃癌根治术（LAG）与传统开腹术（TOS）对Ⅱ、Ⅲ期胃癌的近期及远期疗效。 方法回顾性分析2013年1月至2016年6月陕西中医药大学附属医院行胃癌根治术的患者共136例，根据患者手术方式的不同分为TLG组（45例），LAG组（40例），TOS组（51例）。观察和比较3组患者手术时间、出血量、淋巴结清扫数、术后排气时间、住院时间、术后并发症发生情况，采用Kaplan-Meier法对患者术后5年远期疗效进行生存分析。 结果TLG组患者出血量、排气时间及住院时间低于TOS组及LAG组，LAG组患者手术时间高于TLG组及TOS组，差异均有统计学意义（P<0.05）；3组患者术后并发症发生率比较，差异无统计学意义。共129例获得随访，其中TLG组失访2例，LAG组2例，TOS组3例。TLG、LAG、TOS组平均无瘤生存时间为（53.4±2.1）个月（95%CI=50.45~58.22个月）、（54.3±2.0）个月（95%CI= 47.99~56.18个月）、（52.3±2.1）个月（95%CI=50.98~55.65个月），3组患者无瘤生存时间比较，差异无统计学意义（F=0.519，P=0.772）。 结论TLG术能够在保证患者术后疗效的同时，降低患者术中出血量、排气时间及术后住院时间，TLG术治疗Ⅱ、Ⅲ期胃癌安全可行，疗效显著，值得推广。     

左右半结肠癌病理特征及治疗新策略研究进展

结肠癌患者预后较差，全身系统治疗为目前常用基本策略。近年来的相关研究证据表明，发生在左半结肠和右半结肠的肿瘤病理学特征、分子发病机制及预后存在差异。目前对左、右半结肠癌之间存在的这种异质性差异尚无明确的区分对待策略，国内外指南也尚无定论，因而研究其临床病理特征及相关预后差异具有重要临床意义。笔者在复习相关文献的基础上，就此作一综述。     

腹腔镜扩大左半肝联合全尾叶切除术

1．肝门处预置肝门阻断带，必要时行肝门阻断控制出血；2.肝脏肿瘤压迫第一、二、三肝门及下腔静脉，紧贴肿瘤包膜处理各管道，采取左右结合、由浅入深的策略；3.优先离断肝实质，劈肝后分离出左侧肝蒂，以直线切割闭合器离断左侧肝蒂；4.肝实质内紧贴包块包膜离断肝实质；5.肝脏包块侵犯肝中静脉及右侧尾状叶，术中联合肝中静脉及全尾叶切除；6.术中避免损伤右侧肝蒂及右肝静脉；7.术中使用超声刀、Ligasure等能量器械断肝、止血；8.缝合技术在腹腔镜肝切除手术中具有重要作用。