HMMR促进原发性肝癌细胞增殖且与不良预后的相关性

目的研究透明质酸介导运动因子受体(HMMR)在原发性肝癌中的表达及对肝癌细胞增殖的影响,阐明HMMR的高表达与肝癌患者预后的相关性。方法收集GEO数据库中原发性肝癌患者(GSE121248)的临床信息及基因表达信息,生物信息学分析得到差异基因,设计针对HMMR基因的小干扰RNA载体,通过沉默HMMR基因表达验证其在肝癌细胞增殖中的影响;分析临床信息,阐明其高表达与肝癌患者预后的关系。结果临床大数据生物信息学分析发现HMMR基因在肝癌中明显高表达,免疫组化染色显示原发性肝癌组织中HMMR表达明显高于癌旁肝脏组织,免疫组化打分比较,差异有统计学意义(t=2.953,P=0.0121);利用小干扰RNA敲低HMMR的表达,蛋白免疫印迹(Western blot)与实时荧光定量PCR实验验证小干扰RNA的敲低效率(沉默序列1:t=13.2,P=0.0002;沉默序列2:t=8.668,P=0.0010);平板克隆形成实验表明,低表达HMMR的肝癌细胞(HepG2)的增殖能力明显减低(沉默序列1:t=22.3,P=0.0043;沉默序列2:t=16.63,P=8×10-5);在KM-plotter数据库中分析HMMR基因表达高低对肝癌患者预后的影响,发现高表达HMMR基因的肝癌患者[总体生存率(OS):n=128、无复发生存率(RFS):n=110]OS及RFS明显差于低表达HMMR基因的肝癌患者(OS:n=236、RFS:n=206),[OS:风险比(HR)=2.29(1.62~3.24),P=1.3×10-6、RFS:HR=1.99(1.42~2.78),P=3.5×10-5],进一步分析发现,高表达HMMR的不同分期的肝癌患者的预后不尽相同,提示HMMR可以作为早期肝癌患者的预后标志物。结论HMMR在原发性肝癌患者中明显高表达,促进肝癌细胞的增殖,可以作为早期肝癌患者预后检测的潜在标志物。     

三阴乳腺癌与非三阴乳腺癌临床病理特征差异及与雌激素受体β和表皮生长因子受体表达的关系

  目的  比较三阴乳腺癌与非三阴乳腺癌在临床病理特征及部分免疫组织化学指标表达上的差异, 并探讨这些免疫组织化学指标的表达与三阴乳腺癌临床病理特征及预后的关系。  方法  2010年1月至2013年12月北京协和医院收治的经组织病理确诊的乳腺癌患者共863例, 其中三阴乳腺癌患者135例, 非三阴乳腺癌患者728例。分析三阴乳腺癌与非三阴乳腺癌患者在发病年龄、病理类型、肿瘤大小、分化程度、肿瘤分期、是否有淋巴结转移、是否累及乳头以及手术方式等临床病理特征方面的差异。通过免疫组织化学法检测135例三阴乳腺癌患者与经单纯抽样法选取的135例非三阴乳腺癌患者中雌激素受体β(estrogen receptor β, ERβ)、表皮生长因子受体(epidermal growth factor receptor, EGFR)、P53、Ki67的表达, 分析上述指标在两类乳腺癌中的表达差异。进一步通过单因素生存分析探讨三阴乳腺癌患者的预后相关因素。  结果  三阴乳腺癌中浸润性导管癌的比例高于非三阴乳腺癌(86.7%比65.2%, P < 0.001), 发病年龄低于非三阴乳腺癌[(46.0±10.6)岁比(51.0±13.3)岁, P < 0.05];三阴乳腺癌与非三阴乳腺癌在淋巴结转移、临床分期、肿瘤大小、分化程度、手术方式方面差异亦有统计学意义(P < 0.05);三阴乳腺癌与非三阴乳腺癌在肿瘤累及乳头的比例差异无统计学意义(P > 0.05)。免疫组织化学结果显示, 三阴乳腺癌中ERβ阳性表达率较非三阴乳腺癌显著降低(63.7%比75.6%, P < 0.05), 而EGFR阳性表达率显著升高(62.2%比33.3%, P < 0.05);P53、Ki67在三阴乳腺癌与非三阴乳腺癌中的表达差异无统计学意义(P > 0.05)。与非三阴乳腺癌相比, 三阴乳腺癌的总体生存率(overall survival, OS)和无复发生存率(relapse-free survival, RFS)更低(P < 0.05)。三阴乳腺癌单因素生存分析结果显示, ERβ阴性表达与EGFR阳性表达均与三阴乳腺癌的不良预后相关(P < 0.05)。  结论  相较于非三阴乳腺癌, 三阴乳腺癌有明显不同的临床病理特征:发病年龄较低、原发肿瘤体积较大、分化程度低、易发生淋巴结转移、ERβ阳性表达率较低、EGFR阳性表达率较高、OS及RFS较低。ERβ和EGFR可能成为重要的三阴乳腺癌预后判断指标。     

Expression of survivin and clinical correlation in patients with breast cancer.

Survivin is a member of the inhibitor of apoptosis (IAP) family, which is also involved in the regulation of cell division and is also overexpressed and associated with parameters of poor prognosis in most human cancers, including carcinomas of the lung, breast, colon, stomach, esophagus and pancreas. This study examined the expression patterns of survivin in normal breast tissue, atypical hyperplasia, primary breast cancer and lymph node tissues involved in breast cancer and determined whether the expression of survivin is associated with the characteristics and prognosis of breast cancer. Formalin-fixed paraffin-embedded samples from 80 breast cancer, 20 atypical hyperplasia and 20 malignant lymph node tissue cases were immunostained using polyclonal survivin (Novus Biologicals, CO, USA). The degree of immunostaining was recorded on a scale of 0-3 according to the percentages of staining and distributions within the cytoplasm and nucleus. Survivin was expressed in 52, 14 and 17 of the 80 breast cancer (65%), atypical hyperplasia (70%) and breast cancer lymphoid (85%) specimens, respectively. Among those expressing cancer, 11.3%, 31.3% and 22.5% demonstrated only nuclear staining, only cytoplasmic staining and both nuclear and cytoplasmic staining, respectively. A statistical analysis revealed that cytoplasmic survivin expression was correlated with the stage, histological grade and L/N metastasis. In a Cox proportional hazard model analysis, the expression of survivin was not identified as a significant independent predictor of overall survival (P=0.168), although the decrease in the survival rate of survivin-positive patients did reach statistical significance (P=0.048). CONCLUSION: our results show that survivin is frequently overexpressed in primary breast cancer and its expression gradually increased from normal breast tissue to malignant lymph nodes. The expression of cytoplasmic survivin was common in breast cancer and could be both a useful diagnostic marker and an important source of prognostic information.     

Survivin与非小细胞肺癌预后的相关性研究

目的 研究非小细胞肺癌（NSCLC）组织中细胞凋亡抑制蛋白存活素（Survivin）的表达与其预后的关系。方法 应用免疫组织化学技术对100例手术标本Survivin的表达状态进行检测。结果 100例NSCLC石蜡标本中Survivin阳性率为63％，在不同TNM分期、淋巴结转移的NSCLC组织中，Survivin阳性率的差异有显著性（P〈0．05），而与组织学类型和分化程度无关。多因素COX回归显示：Survivin是NSCLC患者预后的独立预测因子。Survivin阳性患者手术后死亡的相对危险度是Survivin阴性患者的1．86倍；（似然比检验，P〈0．05）。结论 Survivin表达状态是NSCLC患者预后的独立预测因子，Survivin阳性表达的肺癌患者预后不良。     

即刻早期反应基因-1在乳腺癌新辅助化疗后表达的变化及对预后的意义

目的探讨即刻早期反应基因-1(IEX-1)在乳腺癌新辅助化疗(NCT)后表达的变化及在预后判断中的意义。方法选取2012年1月至2017年1月首诊首治并接受NCT的110例乳腺癌女性患者作为研究对象进行回顾性研究,采用二步法免疫组化方法检测NCT前后乳腺癌组织中IEX-1表达的变化,采用Kaplan-Meier和Log-rank法分析其对无病生存期(DFS)及总生存期(OS)的影响。结果 NCT前乳腺癌组织中IEX-1蛋白均阴性;NCT后,IEX-1蛋白阳性表达45例(40. 9%),阴性65例。生存分析显示,IEX-1蛋白阳性表达组患者的DFS、OS均低于IEX-1蛋白阴性表达组(P均<0. 01)。多因素Cox比例风险回归模型分析发现,IEX-1蛋白阳性表达为乳腺癌预后的独立风险因素[HR=4. 921,95%CI=(1. 273~19. 018),P=0. 021]。结论乳腺癌NCT前后检测IEX-1有助于预后判断,IEX-1可能成为乳腺癌NCT疗效的预后指标。     

局部晚期非小细胞肺癌患者心脏受照射剂量与预后的关系

目的探讨心脏放射剂量与局部晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者预后的关系。方法回顾性分析2015年8月至2018年9月于河北省唐山市人民医院接受放射治疗的180例局部晚期NSCLC患者的临床数据和心脏剂量参数,采用K-M分析心脏剂量参数与总生存率的关系,通过多因素COX回归识别NSCLC患者预后的相关因子。结果NSCLC患者的中位生存时间为33.4个月。单因素分析提示计划靶区剂量≥56 Gy(HR1.54,95%CI1.28~2.86,P=0.011)、高血压(HR1.42,95%CI1.34~1.89,P=0.012)、平均心脏剂量≥13.9 Gy(HR1.12,95%CI1.05~2.61,P=0.031)、V5≥70%(HR1.08,95%CI1.01~2.16,P=0.044)、V30≥40%(HR1.16,95%CI1.04~3.01,P=0.041)、V50≥20%(HR1.23,95%CI1.11~2.81,P<0.001)和V60≥5%(HR1.03,95%CI1.00~1.89,P=0.037)是NSCLC患者预后的相关因素。经过多因素调整之后,化疗是NSCLC患者预后的有利因素(HR0.711,95%CI0.35~0.89,P=0.005);患有高血压是预后不良的相关因素(HR1.641,95%CI1.56~1.86,P=0.034);心脏剂量中的V50≥20%(HR1.161,95%CI1.13~3.82,P=0.002)是NSCLC患者预后不良的相关因素。结论心脏剂量中V50是晚期NSCLC患者预后的独立预测因子,心脏照射剂量的增加,可以增加潜在的死亡风险,临床实践中可以通过减少心脏放射剂量来改善患者预后。     

RAD51-G135C和XRCC3-C241T多态性与inv(16)/t(16;16)/CBFβ-MYH11阳性急性髓系白血病预后的关系

目的 探讨DNA同源重组修复基因RAD51-G135C和XRCC3-C241T多态性与inv(16)/t(16;16)/CBβ-MYH11阳性急性髓系白血病(AML)患者预后之间的关系.方法 对染色体核型可供分析且随访资料完整的103例初治原发性inv(16)/t(16;16)/CBβ-MYH11阳性AML患者进行回顾性分析.用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测患者RAD51-G135C、XRCC3-C241T基因多态性.采用单因素(包括性别、初诊时年龄、白细胞计数、血小板计数、血红蛋白含量、染色体核型、KIT基因突变、RAD51-G135C和XRCC3-C241T基因多态性)和多因素分析方法评估患者完全缓解(CR)率、总体生存(OS)率和无复发生存(RFS)率的影响因素.结果 全部患者中位随访时间为28(1-106)个月,总体CR率为92.2%,预期5年OS率和RFS率分别为43.6%(95%CI 37.7%-49.5%)和26.4%(95%CI 21.1%-31.7%),预期中位OS时间和RFS时间分别为53.0(95%CI 33.4～72.7)个月和27(95%CI 22.9-31.1)个月.多因素分析结果显示:高白细胞计数(P=0.004)和年龄＞30岁(P=0.035)是与CR率有关的独立不良预后因素,XRCC3-C241T变异基因型(P=0.007)和高白细胞计数(P=0.009)是与RFS率有关的独立不良预后因素,高白细胞计数(P=0.002)和伴有+8染色体核型异常(P=0.035)是与OS率有关的独立不良预后因素;而RAD51-G135C基因型对此类白血病的预后无明显影响.结论 XRCC3-C241T变异基因型是inv(16)/t(16;16)/CBFβ-MYH11阳性AML一个独立的不良预后因素.

Abstract：

Objective To investigate the impact of polymorphisms of DNA homologous recombination (HR) repair genes RAD51-G135C and XRCC3-C241T on the prognosis of acute myeloid leukemia(AML)with inv(16)/t(16;16)(CBFβ-MYH11).Methods One hundred and three de novo inv( 16)/t(16;16)(CBFβ-MYH11) AML patients were followed-up and retrospectively analyzed.Polymorphisms of RAD51-G135C and XRCC3-C241T were detected by PCR-RFLP.The prognostic factors,including sex, age, white blood cell count, platelet count, hemoglobin level, karyotype, KIT mutation, RAD51-G135C and XRCC3-C241T polymorphisms at diagnosis, for complete remission (CR) achievement, overall survival (OS) and relapse-free survival (RIPS) were analyzed by univariate and multivariate analyses.Results The median follow-up of all patients was 28 (1 - 106) months.The overall CR rate was 92.2%.The estimated 5-year OS and RFS rates were 43.6% (95 % CI 37.7 % - 49.5 % ) and 26.4% (95% CI 21.1% - 31.7% ), and the median OS and RFS were 53 (95%CI33.4 -72.7) and 27 (95%CI22.9 -31.1) months, respectively.In multivariate analysis, higher WBC ( P = 0.004) and older than 30 years of age ( P = 0.035 ) were independent poor factors for CR achievement, the XRCC3-241T variant (P =0.007) and higher WBC (P =0.009)were independent poor factors for 5-year RFS,and higher WBC(P=0.002)and trisomy 8(P=0.035)were independent poor factors for 5-year survival.Polymorphism of RAD5 1-G135C had no significant impact on the prognosis.Conclusion The XRCC3-241T variant is an independent poor prognostic factor for AML with inv(16)/t(16;16)/CBFβ-MYH11.     

Frequent overexpression of aurora B kinase, a novel drug target, in non-small cell lung carcinoma patients

The serine/threonine protein kinase aurora B, a key regulator of mitosis, is emerging as a novel drug target for cancer treatment. Aurora B overexpression has been previously documented by immunohistochemistry in several types of human tumors. We assessed aurora B expression in a series of 160 non-small cell lung cancer (NSCLC) samples (60% stage I, 21% stage II, 11% stage III, and 8% stage IV). In addition, we determined the expression of survivin and p16, two molecules also involved in cell cycle control. Aurora B was expressed selectively in tumor cells compared with normal epithelium. Aurora B expression was significantly correlated with expression of survivin in the nucleus (P < 0.0001), but not with expression of p16 (P = 0.134). High aurora B expression levels were significantly associated with older age (P = 0.012), male sex (P = 0.013), squamous cell carcinoma histology (P = 0.001), poor tumor differentiation grade (P = 0.007), and lymph node invasion (P = 0.037), in the subset of radically resected patients in our series. In addition, aurora B expression predicted shorter survival for the patients with adenocarcinoma histology, at both univariate (P = 0.020) and multivariate (P = 0.012) analysis. Survivin expression levels were neither associated with patient clinicopathologic characteristics nor with survival. However, expression of survivin in the nucleus was preferentially detected in stage I and II than in stage III and IV (P = 0.007) in the overall series of NSCLC samples. Taken together, our results suggest that aurora B may represent a valid target in NSCLC.     

乳腺癌组织中lncRNA PVT1 的表达与患者临床特征及总体生存率的关系

目的　探讨乳腺癌组织中lncRNA PVT1 的表达与患者临床特征及总体生存率的关系。方法　采用实时荧光 定量PCR 法检测乳腺癌组织及其相应癌旁正常组织中lncRNA PVT1 的相对表达量;分析lncRNA PVT1 表达水平与 乳腺癌患者临床特征与总体生存率间的关系。结果　lncRNA PVT1 在乳腺癌组织中的相对表达量显著高于癌旁正常 组织(0.007 5 vs 0.003),其差异具有统计学意义(P=0.0186)。lncRNA PVT1 表达水平与乳腺癌患者的年龄(χ2=5.948, P=0.015)、临床分期(χ2=12.349,P=0.006)、淋巴结转移(χ2=20.942,P<0.001)、远端转移(χ2=5.330,P=0.021) 和 Her2(χ2=5.221,P=0.022) 显著相关。lncRNA PVT1 高表达组患者的总体生存率(overall survival, OS) 显著低于lncRNA PVT1 低表达组,差异具有统计学意义(P=0.036)。结论 　lncRNA PVT1 是一种可预测乳腺癌患者预后的有潜力的生物 学指标。     

Antisense inhibition of survivin expression as a cancer therapeutic

Survivin, a family member of the inhibitor of apoptosis proteins that is expressed during mitosis in a cell cycle-dependent manner and localized to different components of the mitotic apparatus, plays an important role in both cell division and inhibition of apoptosis. Survivin is expressed in a vast majority of human cancers, but not in normal adult tissues. Survivin expression is often correlated with poor prognosis in a wide variety of cancer patients. These features make survivin an attractive target against which cancer therapeutics could be developed. We have identified a survivin antisense oligonucleotide (ASO) that potently downregulated survivin expression in human cancer cells derived from lung, colon, pancreas, liver, breast, prostate, ovary, cervix, skin, and brain as measured by quantitative RT-PCR and immunoblotting analysis. Specific inhibition of survivin expression in multiple cancer cell lines by this ASO (LY2181308) induced caspase-3-dependent apoptosis, cell cycle arrest in the G(2)-M phase, and multinucleated cells. We also showed that inhibition of survivin expression by LY2181308 sensitized tumor cells to chemotherapeutic-induced apoptosis. Most importantly, in an in vivo human xenograft tumor model, LY2181308 produced significant antitumor activity as compared with saline or its sequence-specific control oligonucleotide and sensitized to gemcitabine, paclitaxel, and docetaxel. Furthermore, we showed that this antitumor activity was associated with significant inhibition of survivin expression in these xenograft tumors. On the basis of these, LY2181308 is being evaluated in a clinical setting (Phase II) in combination with docetaxel for the treatment of prostate cancer.     

影响年轻乳腺癌患者新辅助化疗后病理完全缓解及预后的因素分析

目的探讨影响年轻乳腺癌患者新辅助化疗后病理完全缓解(pathological complete response,pCR)和预后的临床病理因素。方法选取2007年1月至2017年12月青岛市第八人民医院乳腺外科收治的年龄≤40岁的行新辅助化疗的女性乳腺癌患者87例临床资料进行回顾性分析。依据病理结果,将其分为pCR组30例,非pCR组57例。对比pCR、复发/转移及死亡人数构成比与临床病理学特点的相关性,并分析pCR与无病生存期(disease-free survival,DFS)和总生存期(overall survival,OS)的关系。结果87例患者新辅助化疗后30例达到pCR(34.5%)。年轻乳腺癌新辅助化疗后的pCR构成比与雌激素受体(estrogen-receptor,ER)、孕激素受体(progesterone receptor,PR)、术前淋巴结状态、Ki67水平及分子分型相关(χ^2值分别为3.592、4.614、8.373、4.251、14.569,P值分别为0.047、0.032、0.039、0.039、0.006);复发转移患者构成比例与ER、PR、人类表皮生长因子受体2(human epidermal growth factor receptor 2,HER-2)、肿瘤大小和淋巴结状态相关(χ2值分别为8.778、6.243、9.413、14.910、23.074,P值分别为0.003、0.013、0.009、0.002、<0.001);死亡患者构成比与ER、PR、HER-2、分级、肿瘤大小和淋巴结状态相关(χ^2值分别为6.686、4.340、11.874、15.707、12.428、26.564,P值分别为0.010、0.037、0.003、<0.001、0.006、<0.001);ER、PR、HER-2、肿瘤大小、术前淋巴结状况及分子分型与DFS相关[HR(95%CI)分别为0.53(0.31~0.93)、2.12(1.21~3.64)、0.46(0.27~0.77)、1.91(1.40~2.62)、2.22(1.55~3.20)、1.21(0.95~1.55),P均<0.05];而ER、PR、HER-2、分级、肿瘤大小及术前淋巴结状况与OS密切相关[HR(95%CI)分别为0.47(0.23~0.98)、2.14(1.03~4.44)、0.37(0.19~0.76)、2.90(1.45~5.79)、1.86(1.24~2.79)、2.22(1.39~3.56),P均<0.05]。33例复发转移的患者中pCR患者5例,占16.7%(5/30);余28例未达到pCR,占所有非pCR患者的49.1%(28/57),两组复发率比较差异有统计学意义(P=0.019)。21例死亡的患者中pCR患者2例,占所有pCR患者的6.7%(2/30);余19例均未达到pCR,占所有非pCR患者的33.3%(19/57),两组病死率比较差异有统计学意义(P=0.026)。结论年轻乳腺癌患者新辅助化疗后的pCR构成比及DFS、OS受多种临床病理因素的影响。     

乳腺癌组织MAL2和IGF-1R蛋白表达与病理特征及预后的相关性研究

目的　探讨乳腺癌组织 T细胞分化蛋白 2（mal T-cell di.erentiation protein 2,MAL2）、胰岛素样生长因子 1受体（ insulin like growth factor 1 receptor,IGF-1R）蛋白表达与病理特征及预后的相关性。方法　选取营口市中心医院 2015年 3月～ 2016年 3月收治的 131例乳腺癌患者,采用免疫组织化学法检测乳腺癌患者癌旁正常组织和癌组织 MAL2和 IGF-1R蛋白表达水平,分析 MAL2和 IGF-1R蛋白水平与不同病理特点及预后的关系,并采用 COX比例风险回归模型分析乳腺癌患者预后影响因素。结果　乳腺癌患者癌组织 MAL2（77.86%）,IGF-1R蛋白（ 80.15% )阳性率显著高于癌旁正常组织 (17.56%,21.37%）,差异有统计学意义（ χ2=95.482,90.540,均 P<0.05）;在不同乳腺癌 TMN分期以及分化程度上 MAL2和 IGF-1R蛋白阳性表达率差异均有统计学意义（ χ2 MAL2=33.545,16.188,χ2IGF-1R=6.533, 12.422,均 P＜ 0.001）。131例乳腺癌患者随访期间,预后较差患者 59例,预后良好患者 72例;预后较差组患者 MAL2（94.92%）,IGF-1R（91.53%）蛋白阳性表达率显著高于预后良好组（ 36.11%,41.67%）,差异均有统计学意义（χ2=18.110,8.727,均 P<0.05）。中低分化、 III～ IV期、MAL2蛋白阳性表达和 IGF-1R蛋白阳性表达是患者不良预后的危险因素（ P<0.05）。结论　MAL2和 IGF-1R蛋白在乳腺癌组织中具有较高的表达水平,且与乳腺癌患者 TMN分期和分化程度具有明显的相关性,可能是患者不良预后的危险因素之一。     

ELISA方法检测乳腺癌患者血清HER2的临床价值

目的：HER2基因扩增和HER2蛋白过表达是乳腺癌患者预后不良的分子标志,是临床指导靶向HER2治疗的标准。肿瘤细胞中HER2蛋白胞外域经蛋白酶裂解脱落入血,血清中HER2水平改变可以用于监测乳腺癌的进展和治疗疗效。本研究旨在分析血清HER2水平与乳腺癌组织HER2表达状态的相关性,并探讨血清HER2水平与临床病理因素的关系,以评价其潜在的临床应用价值。方法：分别采用ELISA和免疫组化方法检测70例乳腺癌患者血清HER2水平和肿瘤组织HER2表达状态,Spearmen秩相关分析二者的相关性,χ2检验分析血清HER2与临床病理因素的关系。结果：乳腺癌患者血清HER2水平和组织HER2表达呈正相关（r=0．686,P〈0．001）;肿瘤直径大于2cm患者血清HER2水平高于小于等于2cm患者（χ2=9．071,P=0．030）;临床II-III期患者血清HER2水平高于I期患者（χ2=9．001,P=0．030）;ER阴性患者血清HER2水平高于ER阳性患者（χ2=16．307,P〈0．0.001）：PR阴性患者血清HER2水平高于PR阳性患者（χ2=16．164,P〈0．001）,而血清HER2水平在不同患者年龄、组织学分级和淋巴结状态等临床病理因素各组间无统计学差异。结论：乳腺癌患者血清HER2水平可以反应肿瘤组织HER2表达状态,其水平升高提示乳腺癌恶性程度高、预后差,是潜在的乳腺癌预后预测和疗效监测的血清学标志,     

长链非编码RNA SERTAD1-1在结直肠癌中的表达及意义

目的 探讨长链非编码RNA-癌基因SEI1-1（lnc-SERTAD1-1）对结直肠癌增殖、迁移及预后的影响。方法 选取125例结直肠癌患者的标本,检测癌组织和癌旁正常组织中lnc-SERTAD1-1的表达水平,分析lnc-SERTAD1-1与临床病理特征的相关性,分析lnc-SERTAD1-1对结直肠癌预后的影响。检测正常人结肠组织细胞CCD-18Co与人结直肠癌细胞HCT15中lnc-SERTAD1-1的表达。慢病毒转染构建含有目的基因lnc-SERTAD1-1过表达的HCT15（HO）及含有空白载体质粒的HCT15（HOC）,检测其lnc-SERTAD1-1以及SERTAD1蛋白的表达,并检测lnc-SERTAD1-1对结直肠癌细胞增殖和迁移能力的影响。结果 与癌旁正常组织比较,lnc-SERTAD1-1在结直肠癌组织（0.002 198±0.000 499 vs. 0.002 998±0.000 392,P < 0.001）和癌细胞（0.000 123±0.000 010 vs. 0.000 182±0.000 012,P = 0.004）中呈低表达水平 ;其表达高低与结直肠癌患者的肿瘤部位、肿瘤大小及肿瘤的大体分型相关（P均< 0.05）。在125例结直肠癌患者中,lnc-SERTAD1-1高表达（≥0.000 970）是其术后总生存及无病生存的独立保护因素（总生存HR = 0.228,95% CI：0.107 ~ 0.485,P < 0.001;无病生存HR = 0.228,95% CI：0.103 ~ 0.506,P < 0.001）。体外实验显示lnc-SERTAD1-1表达上调能抑制结直肠癌细胞的增殖和迁移（P均< 0.05）。结论 lnc-SERTAD1-1通过抑制结直肠癌细胞的增殖和迁移发挥抑癌基因的作用,是结直肠癌重要的预后影响因素。     

血脂异常与乳腺癌患者术后疾病进展的关系

目的 探讨血脂异常与乳腺癌患者术后疾病进展的关系,为乳腺癌的预防和治疗提供新的思路.方法 采用回顾性研究方法,选取2014年1 月至2016年10月徐州医科大学附属医院甲乳外科手术治疗的632例乳腺癌患者为研究对象,收集术前血脂资料和病理资料并随访病情至2019 年11 月.根据术后随访情况将患者分为疾病进展组(n=6...     

SQLE基因表达水平在急性髓系白血病患者预后评估中的价值

目的:在大样本数据分析下确定SQLE表达水平与急性髓系白血病(AML)患者的预后关系.方法:对多个含大样本白血病患者数据的队列包括基因组、转录组、基因芯片表达数据以及临床信息资料进行统计分析.结果:SQLE在AML患者肿瘤细胞中的表达量明显高于健康对照者(P=0.001).在3个AML患者队列中SQLE高表达组比低表达...     

Impact of KRAS mutations on clinical outcomes in pancreatic cancer patients treated with first-line gemcitabine-based chemotherapy

Although erlotinib has become an important therapeutic option in addition to gemcitabine, the high frequency of KRAS mutations in pancreatic cancer probably limits the benefits. We retrospectively studied 136 pancreatic cancer patients with available formalin-fixed paraffin-embedded tumor blocks from 2003 to 2009 to understand the clinical significance of KRAS mutations in pancreatic cancer patients treated with gemcitabine-based chemotherapy. KRAS mutations were analyzed by sequencing codons 12, 13, and 61. In this study, 71 (52.2%) of the 136 pancreatic adenocarcinomas examined harbored a point mutation in codons 12 (n = 70) and 61 (n = 1) of KRAS. KRAS mutation was not associated with clinicopathologic parameters. Patients with KRAS mutations showed a worse response (11.3%) than those with wild-type KRAS (26.2%) and poor survival (mutant KRAS, 5.8 months vs. wild-type KRAS, 8.0 months; P = 0.001). Multivariate analysis revealed good prognostic factors for overall survival as well to moderately differentiated histology (P < 0.001; HR = 0.437, 95% CI: 0.301-0.634), locally advanced disease (P < 0.001; HR = 0.417, 95% CI: 0.255-0.681), response to first-line chemotherapy (P = 0.003; HR = 0.482, 95% CI: 0.297-0.780), and wild-type KRAS (P = 0.001; HR = 0.523, 95% CI: 0.355-0.770). However, the observed survival advantage is derived from the subgroup of patients treated with gemcitabine/erlotinib (9.7 vs. 5.2 months; P = 0.002), whereas no survival difference based on KRAS mutation status is obvious in the other subgroup of patients treated without erlotinib (7.0 vs. 7.0 months; P = 0.121). These results need to be further explored in upcoming prospective studies to provide a rationale for personalized medicine in pancreatic cancer.     

化疗相关性高血糖对儿童急性淋巴细胞白血病预后的影响简

本研究探讨急性淋巴细胞白血病儿童诱导及再诱导治疗期间发生化疗相关性高血糖对预后的影响.对中山大学孙逸仙纪念医院儿科2008年6月-2012年5月160名初发ALL患儿的临床资料进行了回顾性分析.随访至2013年5月,中位随访时间为2.6年（0.08-4.9年）.根据含有左旋门冬酰胺酶（L-asp）及地塞米松两种药物化疗期间的血糖值将患儿分为高血糖组及无高血糖组,采用x2检验分析高血糖的好发因素,Kaplan-Meier法及对数秩检验比较高血糖组与无高血糖组的5年总体生存率及无复发率.结果表明,高年龄组（≥10岁）患儿高血糖的发生率高于低年龄组（43.33％vs19.23％）,差别有统计学意义（P=0.008）,且中、高危组的化疗相关性高血糖发生率高于低危组（26.62％vs4.76％,P=0.017）,而与性别相关性无统计学意义（P=0.059）;高血糖组患儿的5年总体生存率为83.1±6.3％,低于无高血糖组患儿（94.2±2.9％）（P=0.014）;高血糖组的5年无复发率（64.1±8.9％）明显低于无高血糖组（88.6±3.8％）（P＜0.001）.结论：高年龄（≥10岁）、中高危ALL患儿易发生化疗相关性高血糖,高血糖患儿的5年总体生存率及无复发率均低于无高血糖组.