CA724、CA242联合CEA预测结肠癌预后的临床价值研究

目的研究糖链抗原724(CA724)、糖链抗原242(CA242)联合癌胚抗原(CEA)预测结肠癌预后的应用价值。方法回顾性分析本院2013年9月至2015年9月90例经肠镜病理活检证实为结肠癌患者的临床资料,所有患者均接受酶联免疫吸附法(ELISA)检测CA724、CA242及CEA,比较不同肿瘤分期患者CA724、CA242及CEA水平,根据不同预后将患者分为存活组和死亡组,并比较两组患者CA724、CA242及CEA水平。采用受试者工作曲线(ROC)分析CA724、CA242及CEA单独和联合检测对判断预后的价值。结果Ⅳ期患者CEA、CA724及CA242水平显著高于其他分期患者,Ⅲ期患者CEA、CA724及CA242水平显著高于Ⅰ至Ⅱ期患者,Ⅱ期患者CEA、CA724及CA242水平显著高于Ⅰ期患者,差异均有统计学意义(P <0. 05)。死亡组患者CEA、CA724及CA242水平显著高于存活组,差异有统计学意义(P <0. 05)。ROC分析结果显示CEA、CA724及CA242判断患者预后的AUC分别为0. 738、0. 530及0. 682,最佳截断值分别为22. 44 ug/L、29. 49 U/m L及21. 27 U/m L。CEA+CA724+CA242三项联合预测患者预后的敏感度和特异度分别为0. 895和0. 606。结论 CEA、CA724及CA242联合监测有助于评估患者的预后,当CEA、CA724及CA242超过22. 44、29. 49及21. 27时,预后较差,临床应引起重视。

结直肠癌患者体质量指数及临床特征与远期预后的相关性

目的研究结直肠癌患者的体质量指数、血清脂肪因子及一般临床特征,探索体质量指数对结直肠患者远期预后的影响。方法 110例结直肠癌患者依据入院BMI值,分为体质量正常组(对照组,n=62)和超重肥胖组(观察组,n=48),比较两组患者血清脂联素、瘦素、TNF-α与VEGF水平;比较结直肠癌患者不同BMI组基线特征;对术后五年生存情况进行回归分析。结果超重肥胖组患者血清瘦素、TNF-α与VEGF水平均较对照组显著降低,脂联素水平显著高于对照组,差异均具有统计学意义(P <0.05);相关性分析结果表明:BMI与脂联素呈负相关(P <0.05),与瘦素、TNF-α及VEGF呈显著正相关(P <0.05);对两组患者男性比例、年龄、肿瘤大小、肿瘤位置、肿瘤分化程度、淋巴结转移以及TNM分期等资料比较,差异无统计学意义(P> 0.05);生存曲线结果表明:两组患者的生存时间分布差异具有统计学意义(χ^(2)=4.976,P=0.026)。Logistic回归分析结果表明,肿瘤分化程度、淋巴结转移以及TNM分期是五年生存率的危险因素(P <0.05),BMI不是五年生存率的危险因素(P> 0.05)。结论超重肥胖的结直肠癌患者血清脂联素、瘦素、TNF-α与VEGF水平异常表达,其指标水平与BMI有相关性;影响患者远期预后的主要因素是肿瘤分化程度、淋巴结转移以及TNM分期;体质量指数对五年生存率有一定的影响。

结直肠癌Ang-2和CD147的水平及其对预后的预测价值

探讨结直肠癌患者促血管生成素Ⅱ(angiopoietin-2,Ang-2)和簇分笔者医化抗原147 (cluster of differentiation 147,CD147)的水平及其对预后的预测价值。方法:回顾性分析2012年6月~2016年5月笔者医院诊治的260例结直肠癌患者,根据随访结果分为生存组( n =215)和死亡组( n =45),并选择50例结直肠息肉作为对照组,均应用组织芯片技术进行免疫组化结果分析,比较Ang-2和CD147不同表达水平间临床和病理表现的差异及对预后的预测价值。结果:结直肠癌组与对照组患者的年龄、性别、BMI和既往史之间比较差异无统计学意义( P >0.05)。结直肠癌组患者Ang-2及CD147表达水平明显高于对照组( P =0.000)。生存组与死亡组患者的年龄、性别、BMI和既往史之间比较差异无统计学意义( P >0.05)。生存组与死亡组患者的肿瘤部位、病理类型、分化程度、临床分期及治疗方式等资料间比较差异无统计学意义( P >0.05);生存组Ang-2及CD147表达分值明显低于死亡组( P =0.000),淋巴结转移情况明显低于死亡组( P =0.000)。ROC曲线显示,应用Ang-2及CD147表达水平对预测结直肠癌患者预后具有较高的诊断效能,其AUC分别为0.821和0.788,差异无统计学意义(P >0.05);Youden 指数提示Ang-2及CD147表达水平预测结直肠癌患者预后的最佳截点分别为≥4分和≥3分。Ang-2及CD147表达水平预测结直肠癌患者预后的诊断准确率(81.88%,83.33%)、敏感度(81.30%,82.00%)、特异性(83.33%,87.69%)和阳性预测值(87.23%,89.23%)比较,差异无统计学意义( P >0.05)。结论:结直肠癌患者Ang-2和CD147表达水平较高,Ang-2和CD147在预测结直肠癌患者预后中有较高价值,Ang-2≥4分和CD147≥3分可作为提示不良预后的参考指标。

达芬奇机器人与腹腔镜结肠癌根治术围术期指标比较

目的比较达芬奇机器人与腹腔镜结肠癌根治术的临床疗效。方法回顾性分析2013年8月-2017年8月本院普通外科实施结肠癌根治手术的277例患者临床资料,其中行达芬奇机器人结肠癌根治术130例(机器人组),腹腔镜结肠癌根治术147例(腹腔镜组),比较两组围术期相关指标。结果与腹腔镜组相比,机器人组术中出血更少[(84.66±17.38)ml vs(97.38±26.19)ml,P=0.000],住院时间更短[(7.13±2.09)d vs(8.32±1.49)d,P=0.000],住院费用更昂贵[(9.63±1.61)万元vs(6.30±1.77)万元,P=0.000];两组淋巴结清扫数、术后排气时间、术后进食时间、引流管及尿管留置时间、术后并发症发生率等差异均无统计学意义(P均>0.05)。结论达芬奇机器人结肠癌根治术具有与腹腔镜手术相同的安全性和有效性,且出血更少,但费用较高。

运用组织芯片技术检测COX-2在结直肠癌中的表达及其临床意义

目的探讨结直肠癌组织中COX-2的表达及其与各临床病理因素的关系,评价COX-2在结直肠癌预后判断中的价值。方法应用组织芯片技术结合免疫组织化学SABC法,检测126例早中期结直肠癌组织中COX-2的表达情况,回顾性分析COX-2与各临床病理因素及预后之间的关系。结果根据免疫组化染色强度,所有病例被分为COX-2高表达组和低表达组,其中高表达组有32例(25.4%),低表达组有94例(74.6%)。COX-2在结直肠癌中表达情况与年龄、性别、肿瘤大小、肿瘤部位、组织学类型、浸润深度、淋巴是否转移、Dukes分期均无相关。然而,高表达的COX-2与肿瘤复发、特别是血行转移显著相关(P<0.05)。两组之间生存率具有显著差异(P=0.0067),COX-2高表达组术后五年生存率显著低于低表达组。多因素回归模型分析结果显示,在潜在的预后因素中(年龄、性别、肿瘤大小、肿瘤部位、组织学类型、淋巴是否转移、Dukes分期、COX-2表达),COX-2表达和Dukes分期可作为是结直肠癌根治术后独立预后因素,COX-2的检测可作为结直肠癌患者预后判断的一个有价值的指标。结论高表达的COX-2与肿瘤复发、特别是血行转移显著相关,COX-2的检测可作为结直肠癌患者预后判断的一个有价值的指标。应用组织芯片高效检测临床组织样本具有快速、方便、经济、准确的优点。

Overexpression of metastasis-associated in colon cancer 1 predicts a poor outcome of hepatitis B virus-related hepatocellular carcinoma

AIM: To investigate the intratumoral expression of metastasis-associated in colon cancer 1 (MACC1) and c-Met and determine their clinical values associated with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: A retrospective study admitted three hundred fifty-four patients with HBV-related HCC. The expression and distribution of MACC1 and c-Met were assessed by quantitative real-time polymerase chain reaction and immunohistochemistry staining. Prognostic factors influencing survival, metastasis and recurrence were assessed. RESULTS: Intratumoral MACC1 level was found to be associated with HCC disease progression. Both median tumor-free survival (TFS) and overall survival (OS) were significantly shorter in the postoperative HCC patients with high intratumoral MACC1 expression, as compared to those with low intratumoral MACC1 levels (TFS: 34 mo vs 48.0 mo, P < 0.001; OS: 40 mo vs 48 mo, P < 0.01). Multivariable analysis indicated that high MACC1 expression or co-expression with c-Met were independent predictors for HCC clinic outcome (P < 0.001). CONCLUSION: High intratumoral MACC1 expression can be associated with enhanced tumor progression and poor outcome of HBV-related HCC. MACC1 may serve as a prognostic biomarker for postoperative HCC.

S100A4 over-expression underlies lymph node metastasis and poor prognosis in colorectal cancer

AIM:To develop lymph node metastasis(LNM)-associated biomarkers for colorectal cancer(CRC) using quantitative proteome analysis.METHODS:Differences in protein expression between primary CRC with LNM(LNM CRC) and without LNM(non-LNM CRC) were assessed using methyl esterification stable isotope labeling coupled with 2D liquid chromatography followed by tandem mass spectrometry(2D-LC-MS/MS).The relationship to clinicopathological parameters and prognosis of candidate biomarkers was examined using an independent sample set.RESULTS:Forty-three proteins were found to be differentially expressed by at least 2.5-fold in two types of CRC.S100A4 was significantly upregulated in LNM CRC compared with non-LNM CRC,which was confirmed by Western blotting,immunohistochemistry and real-time quantitative polymerase chain reaction.Further immunohistochemistry on another 112 CRC cases showed that overexpression of S100A4 frequently existed in LNM CRC compared with non-LNM CRC(P < 0.001).Overexpression of S100A4 was significantly associated with LNM(P < 0.001),advanced TNM stage(P < 0.001),increased 5-year recurrence rate(P < 0.001) and decreased 5-year overall survival rate(P < 0.001).Univariate and multivariate analyses indicated that S100A4 expression was an independent prognostic factor for recurrence and survival of CRC patients(P < 0.05).CONCLUSION:S100A4 might serve as a powerful biomarker for LNM and a prognostic factor in CRC.

Prognostic significance of bcl-2 and p53 expression in colorectal carcinoma

Objective: This study was designed to detect the expression of bcl-2 and p53 proteins in colorectal carcinomas and to determine their association with the patient survival and stage of the diseases. Methods: Immunohistochemistry method was used to detect the expression of bcl-2 and p53 proteins in 93 cases of colorectal carcinoma. The stain results were obtained by analyzing the clinic-pathological characteristics of patients. Results: Fifty-seven percent (53/93) of the colorectal carcinomas were bcl-2 protein positive. The positive rate of bcl-2 protein in lymph node involvement cases was lower (15/37) than the cases without node involvement (38/58, P<0.01). The positive rate of p53 protein was 43% (40/93) in colon-rectum carcinomas. No significant correlation was observed between p53 protein expression and clinic-pathological manifestations (P>0.05) but the survival was significantly worse (P=0.0001) in the p53 protein positive cases. Neither bcl-2 nor p53 alone was correlated with stage of the disease. When combined bcl-2/p53 status was analyzed, a group with bcl-2(+) and p53(?) had the best prognosis. This group was significantly associated with earlier Dukes’ stages (P=0.1763). In multivariate Cox regression analysis, lymph node involvement and p53 protein expression were two independent factors correlated with survival time. Conclusion: The expression of bcl-2 and p53 represent biological characteristics of colorectal carcinomas. Assessment of both bcl-2 and p53 status may be valuable in predicting the prognosis of patients.

Role of von Willebrand factor levels in the prognosis of stage Ⅳ colorectal cancer: Do we have enough evidence?

Cancer patients usually present a prothrombotic condition. Several clotting-related proteins, such as von Willebrand factor （vWF）, presenting higher plasma concentrations in these patients, may play a key role in this process. Moreover, some of those proteins are currently being characterized as response rate and overall survival markers in metastatic colorectal cancer （MCRC）. In this comment article,

Surgical treatment and prognosis of cancers of hepatic flexure of colon invading the duodenum in 65 patients

Objective： The aim of the study was to discuss surgical treatment of right colon carcinoma of hepatic flexure invading the duodenum. Methods： The 65 patients with right colon carcinoma of hepatic flexure invading the duodenum, treated in our department from 1987 to 2007, were included in this study. Their clinicopathological data were retrospectively reviewed and analyzed. All the cases were divided into three types （local invasion, regional invasion, and cancer with internal fistula） according to duodenal defect, including local invasion （ 2.0 cm）, wide invasion （ 2.0 cm） and the presence of internal fistula. Results： The 25 patients with local invasion underwent en bloc resection of the duodenal wall. Pedicled ileal flap was used to cover the large duodenal defect measuring 2.0–3.0 cm in 5 patients. Dudenojejunostomy was used to reconstruct the large defect measuring more than 5 cm in 3 patients. Conservative resection of right-sided colon was performed in 18 patients with wide invasion. Four patients underwent pancreaticoduodenectomy combined with right hemicolectomy for colon cancer involving the pancreatic head. Ten cases underwent duodenal diverticularization. One patient with anastomotic leakage healed within 3 weeks. Other patients were cured without postoperative complications. The total 3-and 5-year survival rates after surgery were 53.8% and 9.2%, respectively. Conclusion： The surgical procedure to be performed is usually decided according to the cancer location, extent, and duodenal defect and invasion, which are important for prolonging life time, improving of quality of life and prognosis in these patients.

Loss of heterozygosity: An independent prognostic factor of colorectal cancer

AIM: Colorectal cancers result from the accumulation of several distinct genetic alterations. This study was to investigate the frequency and prognostic value of loss of heterozygosity (LOH) and microsatellite instability (MSI) at 14 genetic loci located near or within regions containing important genes implicated in colorectal tumorigenesis. METHODS: We studied colorectal cancers with corresponding normal mucosae in 207 patients (139 males and 68 females, mean age at the time of tumor resection 66.2±12.4 years, range 22-88 years). There were 37 right-sided colonic tumors, 85 left-sided colonic tumors and 85 rectal tumors. The distribution of tumor staging was stage Ⅰ in 25, stage Ⅱ in 73, stage Ⅲ in 68, and stage Ⅳ in 41. We analyzed the LOH and MSI of HPC1, hMSH2, hMLH1, APC, MET, P53, NH23-H1, DCC, BAT25, BAT26, D17S250, MYCL1 and D8S254 with fluorescent polymerase chain reaction and denatured gel electrophoresis. High-frequency LOH was determined to be greater than three, or more than 50% of the informative marker with LOH. High-frequency MSI (MSI-H) was determined as more than four markers with instability (>30%). Correlations of LOH and MSI with clinical outcomes and pathological features were analyzed and compared. RESULTS: The occurrence of MSI-H was 7.25%, located predominantly in the right colons (7/15) and had a higher frequency of poor differentiation (6/15) and mucin production (7/15). LOH in at least one genetic locus occurred in 78.7% of the tumors and was significantly associated with disease progression. Of the 166 potentially cured patients, 45 developed tumor recurrence within 36 mo of follow-up. Clinicopathological factors affecting 3-year disease-free survival (DFS) were TNM staging, grade of differentiation, preoperative CEA level, and high LOH status. Patients with high LOH tumors had a significantly lower DFS (50%) compared with patients with low LOH tumors (84%). Of the patients developing subsequent tumor recurrence, the number and percentage of LOH were 2.97 and 46.8% respectively, similar to the stage IV disease patients. TNM staging had the most significant impact on DFS, followed by high LOH status. CONCLUSION: Clinical manifestations of LOH and MSI are different in colorectal cancer patients. High-frequency LOH is associated with high metastatic potential of colorectal cancers.

Levels of v5 and v6 CD44 splice variants in serum of patients with colorectal cancer are not correlated with pT stage,histopathological grade of malignancy and clinical features

AIM:This study was designed to compare the levels of v5 and v6 splice variants of CD44 evaluated using EITSA test in the serum of patients with colorectal cancer in different stages of progression of the disease estimated in pT stage according to WHO score,histopathological grade of malignancy and some clinicopathological features. METHODS:The serum obtained from 114 persons with colorectal adenocarcinomas was examined using ELISA method,pT stage and grade of malignancy of the tumour were examined in formalin fixed and paraffin embedded materials obtained during operation. RESULTS:Only the level of CD44 v5 in the serum of patients before operation with G2 pT4 tumour was lower than that in other probes and the difference was statistically significant. We did not find any other correlations between the level of v5 and v6 CD44 variants and other evaluated parameters. CONCLUSION:The level of CD44 v5 and v6 estimated by ELISA test in the serum can not be used as a prognostic factor in colorectal cancer.

Prognostic value of cancer stem cell markers CD133, ALDH1 and nuclear β-catenin in colon cancer

Objective： Colon cancer is one of the most common human malignancies. Cancer stem cells （CSCs）, despite being only a small subset of cancer cells, have the capability to self-renew and sustain the tumor. They also have the ability to proliferate. Multiple CSCs-associated markers have been identified in colon cancer including CD133, ALDH1 and β-catenin. The aim of the work was to study the prognostic value of CSCs markers （CD133, ALDH 1 and β-catenin）, as well as their rela- tionship to clinicopathological features of colon cancer. Methods： CD133, ALDH1 and β-catenin proteins expression was as- sessed immunohistochemically in a series of colon cancers and their prognostic significance was evaluated. Results： CD133 expression showed significant relationship to tumor stage and lymph node metastasis （P-value 0.004 ＆ 〈 0.001 respectively）, and near significant relationship to liver metastasis （P-value 0.092）. ALDH1 was significantly associated with tumor grade, stage and nodal metastasis （P-value 0.021,0.001 and 0.026 respectively）, but its relationship to liver metastasis was near sig- nificant （P-value 0.068）. Nuclear β-catenin was significantly related to tumor grade, stage, nodal and liver metastasis （P-value 0.001, 〈 0.001, 〈 0.001 and 0.008 respectively）. Overall survival （OS） was associated inversely with CD133, ALDH1 positivity, and directly with nuclear 13-catenin posiUvity （P-value 〈 0.001,0.0001 and 〈 0.001 respectively）. Also recurrence free survival （RFS） was associated inversely with CD133, ALDH1 and directly with nuclearβ-catenin positivity （P-value 0.0001,0.001 and 〈 0.001 respectively）. Conclusion： CD133, ALDH1 and β-catenin expressions of tumor cells have significant impact upon malignant progression of colon cancer and thus patient survival and tumor recurrence. Hence they can be used to predict outcome of colon cancer patients.

Neural cell adhesion molecule-180 expression as a prognostic criterion in colorectal carcinoma:Feasible or not?

AIM： To evaluate the frequency of neural cell adhesion molecule （NCAM）-180 expression in fresh tumor tissue samples and to discuss the prognostic value of NCAM-180 in routine clinical practice.METHODS： Twenty-six patients （16 men, 10 women） with colorectal cancer were included in the study. Fresh tumor tissue samples and macroscopically healthy proximal margins of each specimen were subjected to flow-cytometric analysis for NCAM-180 expression.RESULTS： Flow-cytometric analysis determined NCAM-180 expression in whole tissue samples of macroscopically healthy colorectal tissues. However, NCAM-180 expression was positive in only one case （3.84%） with well-differentiated Stage Ⅱ disease who experienced no active disease at 30 months follow-up. CONCLUSION： As a consequence of the limited number of cases in our series, it might not be possible to make a generalisation, nevertheless the routine use of NCAM-180 expression as a prognostic marker for colorectal carcinoma seems to be unfeasible and not cost-effective in clinical practice due to its very low incidence.

Analysis of Prognosis of 122 Colorectal Cancer Patients with Concurrent Liver Metastasis

OBJECTIVE To explore prognostic factors and treatmentchoices for colorectal cancer (CRC) patients with concurrent livermetastases (CLM).METHODS The data of the 122 CRC patients with CLM, whowere treated in our hospital from January 2000 to December 2005,were collected. Overall survival rate of the patients in our groupwas analyzed using Kaplan-Meier method, and the univariateand multivariate analyses of the 18 factors affecting the survivalrate, including clinicopathologic factors and treatment methods,were conducted using Log-rank test and Cox regression model(SPSS13.0).RESULTS The median survival time of the 122 patients withCRC was 13 months. The 1, 2, 3 and 5-year survival rate was52.46%, 24.59%, 12.30% and 3.28%, respectively. Univariateanalysis combined with Kaplan-Meier curve revealed that thefactors of prognosis included the size of the primary tumor, thelevels of differentiation, lymphatic status, cancerous ileus (CI),the number, size and distribution of liver metastases, extrahepaticinvolvement, the serum CEA level at diagnosis, treatmentmodality, the extent of primary resection, chemotherapeuticmodality and regimen. Multivariate analysis showed that CI,differentiation levels, serum CEA value at diagnosis and treatmentmodality were the independent prognostic factors of CRC patientswith CLM.CONCLUSION For the CRC patients with CLM, poordifferentiation of the tumor and CI, as well as a high CEAlevel indicate an unfavorable prognosis. Treatment choice is ofspecial significance in treating the CRC patients with CLM, soactive radical excision of the primary tumor and liver metastasisis strongly recommended in the CRC patients with hepaticmetastasis alone. Interventional chemotherapy has advantagescompared with the whole-body chemotherapy via peripheral vein,and the regimen of systemic chemotherapy containing oxaliplatinis preferred.

Influence of the Number of Lymph Nodes Examined on the Prognosis of Patients with Dukes' B and C Colorectal Carcinoma

OBJECTIVE To analyze the influence of the number of lymph nodes examined on the prognosis of Dukes' B and C colorectal cancer patients.METHODS The relationship between the clinicopathologic features of 373 patients with Dukes' B and C colorectal cancer and number of the lymph nodes examined was retrospectively analyzed.The effect of the different number of nodes examined on the prognosis of the patients was appraised RESULTS The overall mean number of retrieved lymph nodes of the 373 patients with Dukes' B and C colorectal cancer was 13.71±9.38.The site and size of the tumor as well as the depth of tumor infiltration were the major reasons which influenced the number of lymph nodes retrieved.The mean number of lymph nodes examined in the colon-cancer patients was 17.51± 12.79,which was significantly more than the 11.09±6.17(P = 0.000)exam-ined in the rectal-cancer patients.The 5-year survival rate of the patients with Dukes' B large intestinal carcinoma,with fewer lymph nodes retrieved(0 to 10),was only 60.4%,while those with more lymph node retrieved(≥10)had a 5-year survival of 77.5%.So there was a significant difference between the two groups.However the number of lymph nodes examined had no effect on prognosis of the patients with Dukes' C large intestinal carcinoma.Separate analysis of the colon and rectal cancers indicated that to improve the 5-year survival rate,the number of retrieved nodes in cases with rectal cancer should be at least 9,and with colon cancer cases at least 13.CONCLUSION In order to guarantee an accuracy of tumor staging for developing a possible postoperative treatment,at least 9 lymph nodes in rec-tal cancer patients or 13 in colon cancer patients should be harvested.

Molecular subtypes of colorectal cancer:Evaluation of outcomes and treatment

Colorectal cancer(CRC) is a biologically heterogeneous disease with diverse clinical outcomes and responses to treatment. In the past two to three decades, a major effort has focused on classifying colorectal cancer subtypes based on causation, etiology, gene expression profiles, different pathways, and translational data from clinical trials. The goal is to uncover prognostic and predictive factors for outcomes in patients with colorectal cancer and to guide therapeutic approaches and management for the improvement of overall survival. Significant advances have been achieved in this area. However, tremendous work is still needed to accomplish the goal of better understanding intratumoral heterogeneity and the influence of the colonic environment, among other facets of colorectal cancer.

Recurrence and survival rates of inflammatory bowel disease-associated colorectal cancer following postoperative chemotherapy:a comparative study

Background and Aim:Inflammatory bowel disease(IBD)is associated with an increased risk of colorectal cancer(CRC).Studies have shown tumorigenetic and histomorphological differences between IBD-associated CRC and non-IBD CRC,suggesting differences in tumor behavior and response to treatment.We aimed to compare tumor recurrence and survival rates following postoperative chemotherapy in CRC patients with and without IBD.Methods:Search of the Cleveland Clinic’s CRC database revealed 65 patients who had IBD-associated CRC and received postoperative adjuvant chemotherapy between 1994 and 2010.Twenty-one patients were excluded due to incomplete clinical data.Propensity score-matching based on age,surgery intent,CRC site,tumor grade,American Joint Committee on Cancer(AJCC)stage and T stage was used to match IBD and non-IBD patients(1:4).Competing risk and Cox regression models were used to analyze differences in disease-free survival and overall survival,respectively.Results:Forty-four patients with IBD-associated CRC were matched to 176 patients with non-IBD CRC.Among IBD patients,29(66%)had ulcerative colitis,14(32%)had Crohn’s disease,and one(2%)had indeterminate colitis.Mean IBD diagnosis age was 28.1±14.5 years,and mean IBD duration at time of CRC treatment was 21.5±12.6 years.Ten(23%)IBD patients had tumor recurrence compared with 34(19%)non-IBD patients(P=.074).There was no significant difference in disease-free survival(hazard ratio[HR]=0.60;95%CI:0.35–1.05;P=0.074)or overall survival(HR=0.87;95%CI:0.54–1.4;P=0.58)between IBD and non-IBD patients.Conclusion:Patients with IBD-associated CRC have comparable rates of tumor recurrence and survival following postoperative chemotherapy as CRC patients without IBD.Prospective studies are needed to confirm these findings and guide therapeutic decisions.

Global changes of 5-hydroxymethylcytosine and 5-methylcytosine from normal to tumor tissues are associated with carcinogenesis and prognosis in colorectal cancer

Aberrant DNA methylation has raised widespread attention in tumorigenesis. In this study, we aimed to investigate the changes of global DNA methylation and hydroxymethylation from normal to tumor tissues in colorectal cancer(CRC) and their association with the prognosis. The levels of genomic 5-hydroxymethylcytosine(5hmC) and 5-methylcytosine(5mC) in cancerous tissues were significantly lower than those in corresponding adjacent normal tissues. The genomic levels of 5mC were significantly positively correlated with 5hmC in normal and cancerous tissues(all P<0.05). The ratio of 5mC in cancerous tissues to matched normal tissues(C/N-5mC) was also significantly positively correlated with the ratio of 5hmC in cancerous tissues to matched normal tissues(C/N-5hmC)(P=0.01). The 5mC levels and C/N-5mC ratios decreased with age(all P<0.05). Higher 5mC and 5hmC levels were found in rectal than in colon tissues(all P<0.05). High levels of 5mC in cancerous tissues and high C/N-5hmC ratios were each associated with lymph node metastasis(all P<0.05). Survival analysis indicated that the C/N-5mC ratio(P=0.04) is an independent protective factor for overall survival. The data showed that patients with a combination of high C/N-5hmC and low C/N-5mC ratios tended to have a worse prognosis(P<0.01). Our findings showed that the C/N-5mC ratio may be an independent prognostic factor for CRC outcome. Patients with both a high C/N-5hmC ratio and a low C/N-5mC ratio exhibited the worst survival, suggesting that 5mC and 5hmC can be used as critical markers in tumorigenesis and prognosis estimation.