两种多西他赛联合化疗方案在局部进展期胃癌术后辅助化疗中的疗效评价

摘要 目的：探讨两种多西他赛联合化疗方案在局部进展期胃癌术后辅助化疗中的疗效和安全性,并分析其对患者生活质量的影响。方法：回顾性分析2015年11月至2018年11月期间本院收治的50例胃癌根治术后病理分期为IIA-IIIC期患者的临床资料,所有患者行多西他赛联合方案辅助化疗。根据不同的多西他赛联合用药方案将患者分为两组：一组为多西他赛联合顺铂、氟尿嘧啶的三药静脉联合腹腔化疗方案（DCF组）,共计20例患者;另一组为多西他赛联合奥沙利铂的两药静脉化疗方案（DP组）,共计30例患者。分析经两种辅助化疗方案治疗后患者的2年无复发生存时间（RFS）、2年总生存时间（OS）、生活质量及不良反应。结果：DCF组2年RFS率、OS率较DP组升高（P<0.05）;DCF组患者出现复发转移的时间明显长于DP组（P<0.05）;两组复发转移部位发生率比较无统计学差异（P>0.05）;化疗后2周,DCF组生活质量改善情况优于DP组（P<0.05）;两组不良反应均可控,患者可耐受,两组不良反应的发生率比较无差异（P>0.05）。结论：两种多西他赛联合化疗方案应用于局部进展期胃癌术后辅助化疗均安全有效,采用三药静脉联合腹腔化疗有助于降低复发转移风险,提高患者的生活质量。     

RNA特异性腺苷脱氨酶1在胃癌中的表达及其临床意义

目的：检测ADAR1在胃癌患者中的表达情况,探讨ADAR1的表达水平对胃癌患者的潜在临床意义。方法：通过基因表达谱数据交互分析（GEPIA）数据库获得了胃癌和正常胃组织样本ADAR1在m RNA水平的表达差异情况,在170例胃癌患者的胃癌和配对组织芯片中,通过免疫组织化学手段检测ADAR1的表达情况,并分析ADAR1的表达和临床特征之间的关系。通过癌症基因组图谱（TCGA）数据库获得胃癌的RNAseq数据（level3）和相应的临床信息,用于分析ADAR1与临床诊疗过程中的潜在相关性。通过Kaplan-Meier Plotter平台获得ADAR1的表达对胃癌患者的预后分析预测,结合组织芯片的评分和临床预后资料进行分析、验证。结果：ADAR1在胃癌组织中异常高表达,差异具有统计学意义（P<0.0001）;其高表达与胃癌的组织学分化程度相关（P=0.044）;性别（HR=2.082,95%CI=1.160-3.736,P=0.014）、淋巴结肿大（HR=1.582,95%CI=1.003-2.496,P=0.049）是影响胃癌患者总生存期的独立危险因素;高表达ADAR1的患者总生存期...     

血清cfDNA、VEGFA与晚期胃癌患者化疗疗效和预后的关系研究

摘要 目的：研究血清循环游离脱氧核糖核酸（cfDNA）、血管内皮生长因子A（VEGFA）与晚期胃癌患者化疗疗效和预后的关系。方法：选取2018年6月~2020年6月在空军第九八六医院接受含奥沙利铂方案化疗的晚期胃癌患者108例,所有患者均接受含奥沙利铂方案化疗,化疗2个周期后,根据实体瘤疗效评价标准（RECIST）1.1版评估疗效分为敏感组和不敏感组,比较两组血清cfDNA、VEGFA水平;随访24个月,Kaplan-Meier生存曲线分析血清cfDNA、VEGFA高表达和低表达组的总生存期（OS）,采用Cox风险比例模型进行预后多因素分析。结果：不敏感组血清cfDNA、VEGFA水平显著高于敏感组（P＜0.05）。cfDNA、VEGFA高表达组患者中位OS均明显短于cfDNA、VEGFA低表达组（P＜0.05）。Cox回归模型单因素分析显示,性别、年龄、部位与晚期胃癌预后无关（P＞0.05）,而TNM分期Ⅳ期、分化程度低分化、有淋巴结转移、化疗疗效不敏感、cfDNA高水平、VEGFA高水平与晚期胃癌预后差显著相关（P＜0.05）。Cox回归模型多因素分析显示,淋巴结转移、化疗疗效不敏感及cfDNA、VEGFA水平高是晚期胃癌患者预后的危险因素（P＜0.05）。结论：血清cfDNA、VEGFA水平检测有助于晚期胃癌患者化疗疗效监测和预后评估。     

MRP在胰腺癌组织中的表达及其临床意义

目的：了解MRP蛋白在胰腺癌组织中的表达情况,并探讨其临床意义。方法：应用免疫组织化学法检测72例胰腺癌组织,10例正常胰腺组织中MRP蛋白的表达,并分析其与临床病理学特征及预后的关系。结果：MRP蛋白在胰腺癌组织中的阳性表达率为91．7％,明显高于其在正常胰腺组织中的表达（p〈0．05）。胰腺癌组织中的MRP蛋白高表达与病理学分级低显著相关（p=0．031）,亦与年龄有关（p〈0．05）,而与肿瘤生长部位、肿瘤大小、淋巴结有无转移、临床分期及神经有无浸润无显著相关性（p〉0．05）。MRP蛋白高表达者的中位生存期明显长于低表达者（21．7个月vs11．1个月,p=0．040）。结论：胰腺癌组织中MRP蛋白的高表达与胰腺癌术后的预后好相关,检测胰腺癌中MRP蛋白的表达具有重要的临床意义。     

胰岛素样生长因子-1受体（IGF—IR）在乳腺癌组织中的表达及其临床意义初探

目的：检测分析胰岛素样生长因子-1受体（IGF-IR）在乳腺癌组织中的表达状况及其临床意义。方法：应用半运用半定量RT-PCR方法分析84例乳腺癌和癌旁正常乳腺组织中IGF—IR基因mRNA的表达水平,并分析其表达与患者临床病理特征及预后之间的关系。结果：乳腺癌组织中IGF-IR基因mRNA表达水平显著高于癌旁乳腺组织,二者具有统计学差别（P〈0．001）。乳腺癌组织中IGF-IR基因mRNA表达水平与肿瘤组织分化程度及乳腺癌患者的TNM分期和淋巴结转移情况显著相关（P值分别是0．005,0．025和0．041）。另外,高表达IGF-IR的乳腺癌患者的五年总体生存率（38．3％）显著高于低表达IGF-1R的患者（49．7％;P=0．009）。多因素COX模型分析结果表明：IGF-IR基因mRNA表达水平是乳腺癌患者的一个独立预后分子（HR=2．78,95％CI：1．94-3．94,P=0．041）。结论：IGF-IR基因表达水平上调在乳腺癌发展过程中起着重要的作用。IGF-IR基因mRNA表达水平有望成为临床乳腺癌患者预后判断的一个重要分子标志物。     

乳腺癌中丝／苏氨酸蛋白激酶Plk1mRNA的表达及其预后价值

目的：检测乳腺癌细胞和组织中丝／苏氨酸蛋白激酶Plk1基因mRNA的表达情况并分析其预后价值。方法：应用半定量RT-PCR方法分析3株人乳腺癌细胞和1株正常乳腺上皮细胞中Plk1基因mRNA的表达水平。同时分析84例乳腺癌及对应的癌旁正常乳腺上皮组织中Plk1mRNA的表达水平。统计学分析Plk1mRNA表达水平与乳腺癌患者年龄、肿瘤大小、组织分化程度、淋巴结转移状况、TNM分期和雌激素受体（ER）等临床病理参数之间的关系,以及与预后之间的关系。结果：Plk1基因mRNA在乳腺癌细胞中的相对表达水平显著高于其在正常乳腺上皮细胞中的相对表达水平（P值均小于〈0．05）。另外,Plk1mRNA在乳腺癌组织中平均表达水平（0．88±0．18）显著高于其在癌旁正常乳腺上皮组织中平均表达水平（0．22±0．10;P〈0．01）。统计学分析结果袁明：Plk1mRNA表达水平和乳腺癌患者的淋巴结转移状况及TNM分期密切相关（P=0．009或0．007）。Kaplan—Meier生存曲线分析结果表明：高Plk1mRNA表达水平的乳腺癌患者的5年无疾病进展率及总体生存率均显著低于低Plk1mRNA表达水平的乳腺癌患者（P=0．0026及0．0136）。COX模型的多因素预后分析结果表明：Plk1基因mRNA表达水平是乳腺癌患者的一个独立的预后因素（HR=4．764,95％CI：1．341-6．123,P=0．0025）。结论：Plk1在乳腺癌组织呈现高表达水平,其mRNA表达水平有望成为临床乳腺癌患者一个重要的预后判断分子指标。     

SNCG在胃癌中的表达及意义

目的：探讨SNCG在胃癌及正常胃粘膜组织中的蛋白和mRNA表达及其与临床病理特征的关系。方法：采用免疫组织化学SP法检测90例胃癌及40例正常胃粘膜组织中SNCG蛋白表达情况,同时应用RT-PCR检测29例胃癌及15例正常胃粘膜组织中SNCG mRNA的表达情况。结果：SNCG蛋白在胃癌组中的表达高于正常胃粘膜组（Uc=7.149,P〈0.05）,胃癌组中SNCG蛋白阳性表达与癌组织的浸润深度以及有无淋巴结转移有关（Uc=2.742,Uc,3.970,P均〈0.05）,而与患者的性别、年龄、及癌组织的分化程度无关。SNCG mRNA在胃癌组织中的表达量明显高于正常胃粘膜组织（t=4.399,P〈0.01）。结论：SNCG在胃癌组织中的高表达与胃癌发生发展及浸润转移密切相关,可能会成为胃癌早期发现、早期诊断以及判断转移、预后的重要参考指标。     

PRR11在胃癌中的表达及其与预后的关系

检测PRR11蛋白在胃癌中的表达,分析其表达异常与胃癌临床指标及预后间的关系。用Western免疫印迹比较胃癌和正常组织中PRR11的表达。构建含167例胃癌的组织芯片,用免疫组化法检测PI汛11蛋白在胃癌组织中的表达,统计学分析其与肿瘤大小、肿瘤侵袭、组织分化、淋巴结转移、TNM分期及胃癌患者总生存期之间的关系。PRR11在胃癌组织中的表达高于癌旁组织,在胃癌中的表达率为50．9％（85／167）,而在癌旁黏膜中不表达或微弱表达。PRR11的表达与胃壁侵袭、淋巴结转移、疾病分期和组织分化呈正相关（P〈0．05）。单因素生存分析表明,PRRll蛋白阳性表达患者较阴性患者生存期短（45个月VS81个月,P〈0．001）。多因素生存分析也表明,PRR11蛋白阳性表达患者生存期短于阴性患者（95％CI：0．347～0．865,P=0．01）。高表达PRR11与胃癌的发生、进展及预后密切相关,是判断胃癌患者预后的重要指标之一。     

胃癌组织长链非编码RNA HIT000218960的表达及其与患者临床病理特征及预后的关系研究

摘要 目的：探讨胃癌组织长链非编码核糖核酸（lncRNA）HIT000218960的表达及其与患者临床病理特征及预后的关系。方法：选择2018年1月至2019年6月于中国人民解放军联勤保障部队第九七Ο医院进行手术切除治疗的103例胃癌患者及进行胃粘膜活检的健康体检志愿者62例,取其对应组织,应用逆转录-定量聚合酶链式反应（RT-qPCR）检测组织中lncRNA HIT000218960及高迁移率族蛋白A2（HMGA2）信使RNA（mRNA）表达,应用免疫组织化学法检测组织中HMGA2阳性表达。分析lncRNA HIT000218960表达与胃癌患者临床病理特征的关系。随访3年,应用Kaplan-Meier生存曲线分析不同lncRNA HIT000218960分组患者预后情况,并应用Cox回归分析胃癌患者预后的影响因素。结果：胃癌组织中lncRNA HIT000218960、HMGA2 mRNA表达水平显著高于正常胃粘膜组织（P<0.05）,HMGA2蛋白阳性表达率显著高于正常胃粘膜组织（P<0.05）。胃癌组织中lncRNA HIT000218960表达与肿瘤直径、组织分化程度、TNM分期、淋巴结转移显著相关（P<0.05）。lncRNA HIT000218960水平与HMGA2 mRNA表达呈正相关（r=0.462,P<0.05）。lncRNA HIT000218960低表达组3年生存率显著高于lncRNA HIT000218960高表达组（P<0.05）。Cox回归显示,肿瘤组织中低分化、TNM分期Ⅲ期、淋巴结转移、lncRNA HIT000218960高表达、HMGA2 mRNA高表达是胃癌患者预后不良的危险因素（P＜0.05）。结论：胃癌组织中存在lncRNA HIT000218960异常高表达,其与胃癌恶性进展及患者预后不良有关。     

外泌体lncRNA-MIR100HG/miR-100表达变化与胃癌临床病理特征、无疾病进展生存率的相关性

摘要 目的：探究胃癌患者血清外泌体长链非编码RNA-MIR100HG（lncRNA-MIR100HG）及微小核糖核酸-100（miR-100）表达情况,并分析其与患者临床病理特征和无疾病进展生存率之间的相关性。方法：收集60例胃癌患者和60例良性疾病患者,提取外泌体,检测lncRNA-MIR100HG/miR-100的表达情况并进行组间比较。采用Pearson相关分析lncRNA-MIR100HG与miR-100表达水平的相关性,应用单因素卡方检验分析与胃癌患者临床病理特征相关性,采用Kaplan-Meier生存分析lncRNA-MIR100HG/miR-100表达情况与无疾病进展生存率。结果：（1）胃癌组患者血清lncRNA-MIR100HG显著高于,miR-100相对表达水平显著低于胃良性疾病组（P<0.05）;（2）Pearson相关分析结果显示血清lncRNA-MIR100HG和miR-100存在显著负相关关系（r=-0.483,P<0.05）;（3）单因素卡方检验分析结果显示：胃癌患者血清lncRNA-MIR100HG相对表达水平与肿瘤大小、分化程度、肿瘤浸润深度、临床分期、淋巴结转移和远处转移相关,血清miR-100相对表达水平与肿瘤大小、分化程度、临床分期和淋巴结转移相关（P<0.05）;（4）血清lncRNA-MIR100HG、miR-100低水平表达胃癌患者PFS显著长于高水平患者（χ²=37.371,P＜0.05）,miR-100高水平表达胃癌患者PFS显著长于低水平患者（χ²=28.631,P＜0.05）。结论：胃癌患者血清外泌体lncRNA-MIR100HG/miR-100表达水平与肿瘤大小、肿瘤浸润深度、临床分期等病理特征相关,lncRNA-MIR100HG高表达与miR-100低表达可能提示胃癌患者预后越差。     

Adjuvant Chemotherapy with Docetaxel,Cisplatin, and Continuous-Infusion 5-Fluorouracil for Gastric Cancer: A Phase II Study

PURPOSE: This study evaluated the efficacy and safety of adjuvant chemotherapy with the docetaxel plus cisplatin and 5-fluorouracil (5-FU) (DCF) regimen in patients with gastric cancer. PATIENTS AND METHODS: Thirty-two patients with gastric or gastroesophageal junction cancer were enrolled in this study after undergoing radical resection. The patients received the following chemotherapy: docetaxel (60 mg/m²) on day 1, cisplatin (12 mg/m² per day) on days 1 to 5, and 5-FU (2500 mg/m²) continuous infusion for 120 hours, repeated every 3 weeks for six cycles. The primary end point was disease-free survival (DFS). RESULTS: The median DFS was 17.0 months. The 1-year DFS was 72%, and the 2-year DFS was 37.5%. The median overall survival was 28.0 months. Using univariate analysis, the technique of lymph node dissection was a predictor for postoperative relapse. The median DFS was 15.0 months in the D1 group and 18.0 months in the D2 group (P = .043). The most frequent grade 3/4 adverse events were neutropenia (56.25%), diarrhea (9.38%), nausea (6.25%), and vomiting (6.25%); 12.5% of patients developed febrile neutropenia. There were no chemotherapy-related deaths. CONCLUSIONS: The modified DCF regimen is an effective adjuvant chemotherapy in gastric cancer. Hematologic toxicity was frequent but manageable. This regimen merits further investigation.     

Prognostic role of human equilibrative transporter 1 (hENT1) in patients with resected gastric cancer

Nucleoside transporter proteins are specialized proteins that mediate the transport of nucleosides and nucleoside analog drugs across the plasma membrane. The human equilibrative nucleoside transporter 1 (hENT1) is a member of these proteins and mediates cellular entry of gemcitabine, cytarabine, and fludarabine. The hENT1 expression has been demonstrated to be related with prognosis and activity of gemcitabine‐based therapy in breast, ampullary, lung, and pancreatic cancer. We investigated the immunohistochemical expression of hENT in tumor samples from 111 patients with resected gastric adenocarcinoma, correlating these data with clinical parameters and disease outcomes. None of the patients received chemotherapy or radiation therapy before or after surgery as a part of an adjuvant or neoadjuvant program. On univariate survival analysis, the hENT1 expression was associated with overall survival (OS) and disease free survival (DFS). Specifically, those patients with overexpression of hENT1 showed a shorter OS (P = 0.021) and a shorter DFS (P = 0.033). Considering only the node positive patients, higher hENT levels were associated with significantly shorter median DFS (21.7 months; 95% CI 11.1–32.4) compared with patients with low expression of hENT1. The hENT1 expression was defined, in the lymph‐node positive patients, as an independent prognostic factor (P = 0.019). Furthermore, considering only patients with diffuse or mixed tumors and lymph‐node positive, the expression of hENT1 was strongly related with DFS and OS. Immunohistochemistry for the hENT1 protein carries prognostic information in patients with resected gastric cancer and holds promise as a predictive factor in chemotherapy decisions. J. Cell. Physiol. 223: 384–388, 2010. © 2010 Wiley‐Liss, Inc.     

Insulin-Like Growth Factor 1 Receptor (IGF1R) Expression and Survival in Operable Squamous-Cell Laryngeal Cancer

Introduction

Prognosis of patients with operable laryngeal cancer is highly variable and therefore potent prognostic biomarkers are warranted. The insulin-like growth factor receptor (IGFR) signaling pathway plays a critical role in laryngeal carcinogenesis and progression.

Patients and Methods

We identified all patients with localized TNM stage I–III laryngeal cancer managed with potentially curative surgery between 1985 and 2008. Immunohistochemical (IHC) expression of IGF1R-alpha, IGF1R-beta and IGF2R was evaluated using the immunoreactive score (IRS) and mRNA levels of important effectors of the IGFR pathway were assessed, including IGF1R, IGF-binding protein 3 (IGFBP3), suppressor of cytokine signaling 2 (SOCS2) and members of the MAP-kinase (MAP2K1, MAPK9) and phosphatidyl-inositol-3 kinase (PIK3CA, PIK3R1) families. Cox-regression models were applied to assess the predictive value of biomarkers on disease-free survival (DFS) and overall survival (OS).

Results

Among 289 eligible patients, 95.2% were current or ex smokers, 75.4% were alcohol abusers, 15.6% had node-positive disease and 32.2% had received post-operative irradiation. After a median follow-up of 74.5 months, median DFS was 94.5 months and median OS was 106.3 months. Using the median IRS as the pre-defined cut-off, patients whose tumors had increased IGF1R-alpha cytoplasm or membrane expression experienced marginally shorter DFS and significantly shorter OS compared to those whose tumors had low IGF1R-alpha expression (91.1 vs 106.2 months, p = 0.0538 and 100.3 vs 118.6 months, p = 0.0157, respectively). Increased mRNA levels of MAPK9 were associated with prolonged DFS (p = 0.0655) and OS (p = 0.0344). In multivariate analysis, IGF1R-alpha overexpression was associated with a 46.6% increase in the probability for relapse (p = 0.0374). Independent predictors for poor OS included node-positive disease (HR = 2.569, p<0.0001), subglottic/transglottic localization (HR = 1.756, p = 0.0438) and IGF1R-alpha protein overexpression (HR = 1.475, p = 0.0504).

Conclusion

IGF1R-alpha protein overexpression may serve as an independent predictor of relapse and survival in operable laryngeal cancer. Prospective evaluation of the IGF1R-alpha prognostic utility is warranted.     

Prospective study on prognostic significance of DNA ploidy and Ki-67 expression in colorectal cancer

The aim of the study was to correlate tumoral DNA ploidy and Ki-67 expression with therapy response, Overall Survival (OS), Disease Specific Survival (DSS) and Disease Free Survival (DFS). Three samples of colorectal cancer were collected from each patient. One sample of normal tissue was our internal control. DNA ploidy was evaluated by FACSCalibur cytometer and Ki-67 by immunohistochemistry. We studied 67 patients and we found aneuploidy in 65,7 percent of carcinoma with a Ki-67 median expression of 55 percent. After surgery and chemotherapy in 35 percent of the patients with aneuploid carcinoma and high proliferative activity (Ki-67 greater than 55 percent) there were no evidence of disease versus 100 percent of patients with DNA diploidy and low proliferative activity (Ki-67 less than 55 percent). Tumoral aneuploidy significantly correlated with lower OS, DSS and DFS (18 percent vs 86 percent at 30 months). Univariated analysis demonstrated a significant correlation between aneuploidy and develop disease progression (p=0,033, odd ratio=5.7), while the cut-off of 55 percent for Ki-67 expression did not correlate with OS, DSS and DFS. Preliminary results (the study is still in progress) seemed to suggest that DNA ploidy has a prognostic and predictive significance in colorectal carcinoma.     

HOXB7在胃癌组织中的表达及其临床意义

目的:分析同源异型盒基因B7(Homeobox B7,HOXB7)在人胃癌组织中的表达情况,并探讨HOXB7的表达与胃癌患者临床病理特征和预后的关系。方法:收集行手术切除的胃癌组织及对应癌旁组织共120例,采用实时定量PCR(q RT-PCR)技术、蛋白印迹(Western blot)和免疫组化染色分别检测HOXB7m RNA水平及蛋白水平在胃癌及对应癌旁组织中的表达,通过卡方检验分析HOXB7表达水平与胃癌患者临床病理因素间的相关性,采用单因素及多因素Cox回归模型评估HOXB7在胃癌风险评估中的作用,Kaplan-Meier生存曲线分析HOXB7表达水平与胃癌患者无瘤生存期和总生存期的关系。结果:胃癌组织中HOXB7 m RNA和蛋白表达水平均显著高于对应癌旁组织(P0.05);HOXB7蛋白表达与肿瘤临床分期、浸润深度及淋巴结转移均具有显著相关性(P0.05),而与患者性别、年龄、分化程度及远处转移均无显著相关性(P0.05)。单因素和多因素Cox分析提示HOXB7可以作为评估胃癌患者预后的独立风险因素。Kaplan-Meier生存分析结果显示高表达HOXB7的胃癌患者无瘤生存时间和总生存时间均显著低于HOXB7低表达患者组(P0.01)。结论:HOXB7蛋白在胃癌组织中高表达,并与胃癌的恶性表型有关,可能参与胃癌发生及恶性进展过程,可作为判断胃癌患预后的重要参考指标。     

Decreased tumstatin-mRNA is associated with poor outcome in patients with NSCLC

Tumstatin is a candidate tumor suppressor that plays an important role in tumor growth and angiogenesis. The purpose of this study was to evaluate the correlation between tumstatin-mRNA expression and the clinicopathologic characteristics, tumor angiogenesis, outcome of patients with non-small cell lung cancer (NSCLC). Specimens from 68 patients with NSCLC were recruited in this study. Tumstatin-mRNA expression and protein level in tumor tissues were quantified respectively by quantitative RT-PCR and ELISA. Microvessel density (MVD) was determined by CD34 immunostaining. The correlation of tumstatin-mRNA expression levels with clinicopathologic variables, tumor angiogenesis, and prognosis was analyzed. Tumstatin-mRNA expression levels were decreased in tumor. Tumstatin-mRNA expression level was significantly correlated with its protein level in tumor (r = 0.562; P = 0.001). Tumstatin-mRNA expression levels in poorly differentiated tumor tissues were significantly lower than in well-differentiated tumor tissues (P < 0.004). Furthermore, tumor tumstatin-mRNA expression were also significantly related to tumor pathologic stage (P = 0.032) and MVD (r = -0.77, P < 0.0001). Overall survival (OS) and disease-free survival (DFS) analysis indicated that NSCLC patients with low tumstatin-mRNA expression had poorer OS and DFS than those with high expression (P = 0.015 and 0.037; respectively). Multivariable Cox regression analysis revealed that the tumstatin-mRNA expression could be an independent prognostic indicators in both DFS and OS. Tumstatin-mRNA expression levels are down-regulated in NSCLC tissues. Tumstatin-mRNA expression level correlates with prognosis, which suggests that tumstatin-mRNA is a new potential independent marker of favorable prognosis in NSCLC.     

ERCC1 and TS Expression as Prognostic and Predictive Biomarkers in Metastatic Colon Cancer

In patients with metastatic colon cancer, response to first line chemotherapy is a strong predictor of overall survival (OS). Currently, oncologists lack diagnostic tests to determine which chemotherapy regimen offers the greatest chance for response in an individual patient. Here we present the results of gene expression analysis for two genes, ERCC1 and TS, measured with the commercially available ResponseDX: Colon assay (Response Genetics, Los Angeles, CA) in 41 patients with de novo metastatic colon cancer diagnosed between July 2008 and August 2013 at the University of California, San Diego. In addition ERCC1 and TS expression levels as determined by RNAseq and survival data for patients in TCGA were downloaded from the TCGA data portal. We found that patients with low expression of ERCC1 (n = 33) had significantly longer median OS (36.0 vs. 10.1 mo, HR 0.29, 95% CI .095 to .84, log-rank p = 9.0x10^-6) and median time to treatment to failure (TTF) following first line chemotherapy (14.1 vs. 2.4 mo, HR 0.17, 95% CI 0.048 to 0.58, log-rank p = 5.3x10^-4) relative to those with high expression (n = 4). After accounting for the covariates age, sex, tumor grade and ECOG performance status in a Cox proportional hazard model the association of low ERCC1 with longer OS (HR 0.18, 95% CI 0.14 to 0.26, p = 0.0448) and TTF (HR 0.16, 95% CI 0.14 to 0.21, p = 0.0053) remained significant. Patients with low TS expression (n = 29) had significantly longer median OS (36.0 vs. 14.8 mo, HR 0.25, 95% CI 0.074 to 0.82, log-rank p = 0.022) relative to those with high expression (n = 12). The combined low expression of ERCC1/TS was predictive of response in patients treated with FOLFOX (40% vs. 91%, RR 2.3, Fisher’s exact test p = 0.03, n = 27), but not with FOLFIRI (71% vs. 71%, RR 1.0, Fisher’s exact test p = 1, n = 14). Overall, these findings suggest that measurement of ERCC1 and TS expression has potential clinical utility in managing patients with metastatic colorectal cancer.     

Pre-treatment systemic immune-inflammation index is a useful prognostic indicator in patients with breast cancer undergoing neoadjuvant chemotherapy

The systemic immune-inflammation index (SII = N × P/L) based on neutrophil (N), platelet (P) and lymphocyte (L) counts is used to predict the survival of patients with malignant tumours and can fully reflect the balance between host inflammatory and immune status. This study is conducted to explore the potential prognostic significance of SII in patients with breast cancer undergoing neoadjuvant chemotherapy (NACT). A total of 262 patients with breast cancer received NACT were enrolled in this study. According to the receiver operating characteristic curve, the optimal cut-off value of SII was divided into two groups: low SII group (<602 × 10⁹/L) and high SII group (≥602 × 10⁹/L). The associations between breast cancer and clinicopathological variables by SII were determined by chi-squared test or Fisher's exact test. The Kaplan-Meier plots and log-rank test were used to determine clinical outcomes of disease-free survival (DFS) and overall survival (OS). The prognostic value of SII was analysed by univariate and multivariate Cox proportional hazards regression models. The toxicity of NACT was accessed by National Cancer Institute Common Toxicity Criteria (NCICTC). According to univariate and multivariate Cox regression survival analyses, the results showed that the value of SII had prognostic significance for DFS and OS. The patients with low SII value had longer DFS and OS than those with high SII value (31.11 vs 40.76 months, HR: 1.075, 95% CI: 0.718-1.610, P = .006; 44.47 vs 53.68 months, HR: 1.051, 95% CI: 0.707-1.564, P = .005, respectively). The incidence of DFS and OS in breast cancer patients with low SII value was higher than that in those patients with high SII value in 3-, 5- and 10-year rates. The common toxicities after NACT were haematological and gastrointestinal reaction, and there were no differences by SII for the assessment of side effects of neoadjuvant chemotherapy. Meanwhile, the results also proved that breast cancer patients with low SII value and high Miller and Payne grade (MPG) survived longer than those breast cancer with high SII value and low MPG grade. In patients without lymph vessel invasion, these breast cancer patients with low SII value had better prognosis and lower recurrence rates than those with high SII value. Pre-treatment SII with the advantage of reproducible, convenient and non-invasive was a useful prognostic indicator for breast cancer patients undergoing neoadjuvant chemotherapy and is a promising biomarker for breast cancer on treatment strategy decisions.     

大肠癌组织中TS和COX-2的表达及其与患者无病生存期的关系

目的:探讨大肠癌患者癌组织中环氧化酶-2(COX-2)、胸苷酸合成酶(TS)的表达及其与患者无病生存期的关系。方法:筛选我院收治的大肠癌根治术患者,选择无病生存期大于48个月者30例和无病生存期小于48个月者29例。采用免疫组化法检测大肠癌组织中COX-2和TS的表达,并分析其与患者无病生存期的关系。结果:49例结直肠癌患者中,TS的阳性表达率为91.84%,COX-2的阳性表达率为77.55%。不同无病生存期的大肠癌患者TS的表达水平比较无统计学差异(P=0.646)。COX-2在无病生存期48个月的患者癌组织中表达水平明显低于无病生存期48个月的患者,差异有统计学意义(P=0.033)。结论:COX-2与大肠癌患者的无病生存期显著相关,可能成为预测大肠癌预后的参考指标。