TS、DPD、TP和OPRT基因表达在预测胃癌患者治疗效果中的价值

[目的]本实验通过分析胃癌病例样本中胸苷酸合酶(TS)、二氢嘧啶脱氢酶(DPD)、胸苷酸磷酸化酶(TP)和乳清酸磷酸核糖基转移酶(OPRT)基因的表达情况,鉴定了这些基因作为生物标志物在S-1制剂辅助参与的胃癌治疗中的作用。[方法]符合纳入标准并且采样结果可纳入分析的病例共计274例。所有病例样本均进行甲醛浸泡并切片观察和保存,显微切割肿瘤样本后进行RT-PCR以检测TS,DPD,TP和OPRT基因表达,并根据看家基因β-肌动蛋白表达量进行量化比较。对每个基因的表达量以25%,50%和75%进行表达量高低的分组。[结果]在根据TS表达量高低进行的分组中,在S-1治疗组和仅手术治疗组的对比结果显示,在TS高表达量组(≥75%,HR=0.35,95%CI0.21~0.61)中患者生存风险比(HR)显著低于(P=0.01)TS低表达量组(75%,HR=0.74,95%CI0.56~1.01)。根据DPD表达量进行的分组中与TS表达组检测结果类似,S-1治疗可显著降低DPD高表达组的HR。但在TP和OPRT表达组中并未发现类似结果,且患者生存情况与TP和OPRT表达量亦无相关性。[结论]本研究显示S-1辅助手术治疗对于胃癌患者预后效果更好;基因TS和DPD高表达与S-1辅助治疗的良好预后存在相关性,但基因TP和OPRT的表达与S-1治疗没有关联。     

胃癌组织TS表达及其临床意义

目的探讨胸苷酸磷酸合成酶(TS)在胃癌组织中的表达变化及其在胃癌发生和发展中的作用。方法选择经临床病理确诊的胃癌患者140例,采用免疫组化SP法检测胃癌组织和癌旁正常组织TS表达,并分析TS表达与胃癌患者临床病理特征、治疗效果、化疗后不良反应和生存时间的关系。结果TS在胃癌组织中阳性表达率为67.86%(95/140),癌旁正常胃黏膜组织中阳性表达率为22.22%(20/90),差异具有统计学意义(P<0.05)。胃癌组织中TS阳性表达与分化程度相关(P<0.05),但与患者性别、年龄、肿瘤大小、淋巴结是否转移、临床分期无明显相关性(P>0.05)。在可评价的84例胃癌患者中,TS阳性表达组化疗有效率为28.07%(16/57),TS阴性表达组化疗有效率为74.07%(20/27),差异具有统计学意义(P<0.05)。TS阳性表达组与阴性表达组在恶心呕吐、口腔黏膜炎、腹泻等不良反应中无明显差异(P>0.05)。TS阳性表达组的1年生存率为52.63%(30/57),阴性表达组1年生存率为48.15%(13/27),差异无统计学意义(P>0.05)。结论TS在胃癌组织中的阳性表达率明显高于癌旁组织,TS表达与分化程度相关,但与其他临床病理特征无关,TS表达可作为氟尿嘧啶类药物化疗疗效判断较为有价值的指标,但对化疗毒副反应和预后的判断无明确的参考意义。     

大肠癌TP及DPD表达与临床特征的关系

目的:探讨大肠癌中TP和DPD的表达与临床病理特征的关系.方法:采用ELISA和免疫组织化学技术检测54例大肠癌肿瘤及邻近正常组织中TP和DPD的表达,比较酶表达水平与临床病理特征之间的关系.结果:大肠癌肿瘤组织中TP含量显著高于正常组织(1026±492vs387±226μkat/gprotein,P<0.01),DPD蛋白含量在肿瘤与正常组织间无显著差别(P=0.510);TP表达与淋巴结转移程度(P=0.003)和Dukes分期(P=0.026)密切相关,而DPD在男性患者(P=0.023)、有黏液腺癌成分者偏高(P=0.013).免疫组化检测大肠癌组织中TP表达阳性率为53.7%(29/54),DPD阳性率为44.4%(24/54);TP倾向表达于有淋巴结转移(P=0.016)和Dukes分期较晚(P=0.075)的病例中,DPD表达与性别关系显著(P=0.044).结论:大肠癌肿瘤组织中TP水平显著高于正常组织,与临床分期密切相关,而DPD水平在肿瘤与正常组织间无明显差异,女性患者的DPD表达水平低于男性.     

老年晚期结直肠癌患者肿瘤组织胸苷酸合成酶表达与氟尿嘧啶敏感性、副反应及预后的关系

目的探讨老年晚期结直肠癌患者肿瘤组织中胸苷酸合成酶(TS)阳性表达情况及其与氟尿嘧啶(5-Fu)敏感性、副反应及预后的关系。方法接受5-Fu方案化疗且病理明确的结直肠癌患者采用免疫组化法检测肿瘤组织及癌旁(距病灶边缘5 cm)的正常大肠组织中TS表达情况。同时分析TS对5-Fu化疗敏感性、毒副作用及患者预后的影响。结果结直肠癌组织中TS阳性表达率〔74.36%(58/78)〕显著高于正常癌旁组织〔10.26%(8/78)〕(P0.05)。TS表达与结直肠癌患者淋巴结转移、阳性淋巴结数、分化程度、浸润程度有关(P0.05)。TS阳性表达患者恶心呕吐、骨髓抑制、腹泻、口腔黏膜炎化疗毒副反应率显著高于TS阴性患者(P0.05)。结论 TS高表达水平与结直肠癌发生及病情进展具有密切的关系。结直肠癌组织中TS表达可作为患者化疗敏感性、化疗副反应及预后的评价指标。     

替吉奥治疗胃癌的临床疗效与外周血内DPD mRNA和TS mRNA表达水平的相关性

目的分析替吉奥(S-1)治疗胃癌的临床疗效与外周血内二氢嘧啶脱氢酶(Dihydropyrimidine dehydrogenase,DPD)mRNA和胸苷酸合成酶(Thymidine synthetase,TS)mRNA表达水平的相关性。方法选取唐山市人民医院2013年3月-2014年3月接受含S-1方案治疗的75例胃癌患者为研究对象,并进行前瞻性分析。患者化疗前抽取空腹静脉血7 ml,并检测其DPD mRNA、TS mRNA表达水平。结果 Lauren分型为肠型患者的DPD mRNA高表达率高于弥漫型患者;有远处转移患者的TS mRNA高表达率高于无远处转移者(P0.05)。疗效判定为进展(PD)的患者,DPD、TS mRNA表达水平高于部分缓解(PR)、稳定(SD)患者;PR患者外周血DPD、TS mRNA表达水平低于SD患者(P0.05)。DPD mRNA、TS mRNA表达与临床疗效均呈负相关(r=-0.713,r=-0.735,P0.05)。不同毒副作用分级患者外周血DPD mRNA与TS mRNA表达比较,差异无统计学意义(P0.05)。外周血DPD mRNA及TS mRNA高表达患者OS低于低表达患者(P0.05)。结论根据患者外周血DPD mRNA和TS mRNA表达水平可早期评估患者预后及治疗效果,为胃癌患者生存质量的改善奠定基础。     

TS和BRCA1在胃癌组织中的表达及其临床意义

目的:评价胸苷酸合成酶(thymidylate synthase,TS)和乳腺癌易感基因1(breast cancer susceptibility gene-1,BRCA1)过表达与胃癌患者临床病理参数间的相关性及其临床意义.方法:收集2011-01/2012-01在中国人民解放军南京军区福州总医院手术切除的临床资料完整的246例胃腺癌标本,采用Elivision plus免疫组织化学染色方法检测胃癌组织中TS和BRCA1的表达.使用SPSS16.0软件进行2检验分析.结果:TS和BRCA1在胃癌组织中阳性率分别为39.02%(96/246)、55.69%(137/246);TS蛋白表达与患者性别、年龄、肿瘤部位、TNM分期、分化程度、浸润深度、淋巴结转移、远处转移均无相关性(P>0.05);BRCA1蛋白表达与患者性别、年龄、肿瘤部位、TNM分期、分化程度远处转移无相关性(P>0.05),而与浸润深度(P<0.01)和TNM分期(P<0.05)相关.胃癌组织中TS和BRCA1共同表达阳性率为26.02%(64/246),联合分析显示TS和BRCA1表达呈负相关(P<0.01,Pearson列联系数C=0.2472).结论:胃癌组织中存在TS和BRCA1过表达,BRCA1蛋白表达与TNM分期和浸润深度相关,提示BRCA1表达和肿瘤侵袭性具有相关性,可作为评估胃癌生物学行为以及预后的参考指标.BRCA1和TS的表达检测有助于临床化疗药物的选择.     

胸苷酸合成酶的表达及其对胃癌化疗敏感性的预测

[目的]探讨胃癌组织中胸苷酸合成酶（TS）的表达及其对胃癌患者化疗敏感性的预测价值。[方法]60例胃癌患者均接受2个周期DDP/5-Fu化疗。DDP15-20 mg/（m^2·d）静脉滴注d1-5;5-Fu 375-500 mg/（m^2·d）静脉滴注8 h,d1-5,休息4周后,进行第2个周期化疗。采用免疫组织化学染色法（SP法）检测60例胃癌胃黏膜石蜡标本中TS的表达情况。[结果]60例胃癌标本中TS蛋白高表达者29例（48.3%）,低表达者31例（51.7%）;TS低表达患者的化疗有效率（64.5%）明显高于TS高表达者（34.5%）（P〈0.05）。[结论]胃癌组织中TS蛋白表达水平对应用DDP/5-Fu治疗胃癌的疗效具有一定预测价值。     

ERCC1、TS及MS状态在老年Ⅲ、Ⅳ期胃癌新辅助化疗中的变化及意义

目的通过检测核苷酸切除修复交叉互补基因(ERCC)1、胸苷酸合成酶(TS)、错配修复(MMR)蛋白(PMS2、MLH1、MSH2、MSH6)在老年Ⅲ、Ⅳ期胃癌新辅助化疗前后的表达情况,探讨TS、ERCC1和微卫星(MS)状态与老年Ⅲ、Ⅳ期胃癌新辅助化疗之间的关系。方法老年Ⅲ、Ⅳ期胃癌患者66例,应用FOLFOX6方案进行新辅助化疗后给予手术治疗,分别检测活检组织和手术标本中上述蛋白的表达,分析TS、ERCC1的表达情况和MS状态对新辅助化疗的影响,并分析TS、ERCC1和MS状态在化疗前后变化的关系。结果 TS和ERCC1在化疗后表达下降(P0.001,P=0.024)。化疗前与MS稳定(MSS)患者相比,MS不稳定性(MSI)患者化疗有效率升高(P=0.007)。结论Ⅲ、Ⅳ期结直肠癌患者中MSI预示着较好的新辅助化疗疗效,MS状态可作为Ⅲ～Ⅳ期结直肠癌患者新辅助化疗疗效的预测指标。     

胃癌患者胸苷磷酸化酶的表达与以氟尿嘧啶类药物为基础化疗方案的敏感性:系统评价与Meta分析

[目的]评价胃癌患者胸苷磷酸化酶(TP)的表达与以氟尿嘧啶类药物为基础化疗方案的敏感性的关系。[方法]采用Cochrane系统评价方法,通过检索CNKI、Wanfangdata、PubMed、Springerlink、Cochrane library等数据库,收集国内外公开发表的所有相关病例对照研究。应用Stata 12.0软件进行Meta分析。[结果]共纳入10篇文献包含TP与临床胃癌化疗敏感性相关,且一线化疗方案以氟尿嘧啶类药物为主的病例对照研究,累计TP阳性表达病例共289例,累计TP阴性表达共21 2例。结果显示10篇文献具有同质性,χ~2=7.84,P=0.550,I~2=0%,TP表达阳性的患者与TP表达阴性的患者对以氟尿嘧啶类为基础的化疗方案敏感性差异有统计学意义,OR=2.531,95%CI(1.702~3.762),[结论]TP表达阳性的胃癌患者对以氟尿嘧啶类为基础的化疗方案有较为明显的敏感性。     

胸苷磷酸化酶在胃癌中的表达及其与细胞增殖的关系

目的　探讨胃癌中胸苷磷酸化酶(TP)表达的意义及其与细胞增殖的关系。方法　 用免疫组化SP法检测69例不同胃黏膜组织中TP和增殖细胞核抗原(PCNA)的表达情况。结果 　胃癌组织及淋巴结胃癌转移灶中,TP的表达较正常胃黏膜及慢性胃炎组显著增高(P<0.05)。 TP表达与胃癌患者的性别、年龄及肿瘤的分化程度无关。肿瘤≥5cm组及T3-4组TP阳性率 (79.17%,87.50%)分别高于肿瘤<5cm组和T1-2组(40%,47.83%);淋巴结转移阳性组中TP表 达(17/21例)明显高于阴性组(8/18例);有远处转移的胃癌组TP阳性率(100%)高于无远处转移 组(56.25%);临床Ⅲ-Ⅳ期胃癌组TP的阳性率(88.24%)高于Ⅰ-Ⅱ期组阳性率(45.45%),P< 0.05。TP表达阳性的胃癌患者中PCNA阳性率(92.00%)高于TP阴性组(57.14%),P<0.05。结 论　胃癌组织中TP表达增高并与肿瘤进展的临床病理参数有关,TP可能有促进肿瘤细胞增殖的 作用,联合检测TP与PCNA是判断胃癌患者预后的较好指标之一。     

Relationship between expression of 5-fluorouracil metabolic enzymes and 5-fluorouracil sensitivity in esophageal carcinoma cell lines

SUMMARY.  5-Fluorouracil (5-FU) is a key drug in the treatment of esophageal squamous cell carcinoma (ESCC). Gene expression of 5-FU metabolic enzymes such as thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyl transferase (OPRT), has recently been investigated in order to predict the 5-FU sensitivity of several cancers. We examined the relationship between such gene expression and 5-FU sensitivity in 25 ESCC cell lines. TS , DPD , TP and OPRT mRNA levels were assessed by real-time polymerase chain reaction. The 50% inhibitory concentrations (IC50) of 5-FU in 25 ESCC cell lines were determined by cell proliferation assay. IC50 values for 5-FU ranged from 1.00 to 39.81 µmol/L. There were significant positive correlations between IC50 and TS mRNA expression ( R ² = 0.5781, P  < 0.0001) and DPD mRNA expression ( R ² = 0.3573, P  = 0.0016). There were no correlations between IC50 and TP or OPRT mRNA expression. TS and DPD mRNA expression levels may be useful indicators in predicting the anti-tumor activity of 5-FU in ESCC.     

Correlation of thymidylate synthase,thymidine phosphorylase and dihydropyrimidine dehydrogenase with sensitivity of gastrointestinal cancer cells to 5-fluorouracil and 5-fluoro-2′-deoxyuridine

AIM:To determine the expression levels of three metabolic enzymes of fluoropyrimidines:thymidylate synthase (TS),thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) in seven human gastrointestinal cancer cell lines,and to compare the enzyme levels with the sensitivity to 5-fluorouracil (5-FU) and 5-fluoro-2′-deoxyuridine (FdUrd).METHODS:TS,TP and DPD mRNA levels were assessed by semi-quantitative RT-PCR,TP and DPD protein contents were measured by ELISA. Fifty percent inhibitory concentrations of growth (IC50),representing the sensitivity to drugs,were determined by MTT assay.RESULTS:IC50 values ranged from 1.28 to 12.26μM for 5-FU,and from 5.02 to 24.21μM for FdUrd,respectively.Cell lines with lower DPD mRNA and protein levels tended to be more sensitive to 5-FU (P&lt;0.05), but neither TS nor TP correlated with 5-FU IC50 (P&gt;0.05).Only TS mRNA level was sharply related with FdUrd sensitivity (P&lt;0.05),but TP and DPD were not (P&gt;0.05).A correlation was found between mRNA and protein levels of DPD (P&lt;0.05),but not TP (P&lt;0.05).CONCLUSION:DPD and TS enzyme levels may be useful indicators in predicting the antitumor activity of 5-FU or FdUrd,respectively.     

Thymidine phosphorylase, dihydropyrimidine dehydrogenase and thymidylate synthase mRNA expression in primary colorectal tumors—correlation to tumor histopathology and clinical follow-up

Aim Evaluation of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), and thymidylate synthase (TS) mRNA levels in formalin-fixed, and paraffin-embedded tissues of patients with colorectal cancer and their prognostic and/or predictive value.Materials and methods Total RNA was isolated from microdissected, formalin-fixed, and paraffin-embedded tissues (controls and tumor) and subjected to quantitative RT-PCR (QRT-PCR) in the LightCycler system. Resulting mRNA levels correlated to tumor histology (n=102) and the clinical follow-up in patients treated by resection alone (n=40) and by resection plus adjuvant 5-FU-based chemotherapy (n=52).Results Correlation to histopathological parameters revealed a significant association between tumor stage and the TP mRNA level (T and N category and UICC) as well as the TP:DPD (T and N category and UICC) and TS:DPD (T category) ratio. In addition, tumor differentiation was correlated to the TS mRNA level and the TS:DPD ratio. Finally, the TS:DPD ratio was a prognostic marker for overall survival in patients receiving resection alone (p=0.032). Moreover, a high TP:DPD ratio (>8.1; p=0.002) and, marginally, low DPD (<8.2; p=0.05) mRNA levels significantly correlated to disease-free survival.Conclusion We present a novel, standardized approach for TP, DPD, and TS mRNA quantification in archival tissue specimens and applied this to a large series of primary colorectal tumors. Correlations to histopathological parameters and clinical follow-up revealed an association of TP, DPD and TS mRNA expression patterns with tumor stage and suggested new prognostic and predictive markers for patients with colorectal cancer.     

Comparative analysis of thymidylate synthase, thymidine phosphorylase and dihydropyrimidine dehydrogenase expression in colorectal cancer and surrounding normal tissue

Thymidylate synthase [TS], thymidine phosphorylase [TP] and dihydropyrimidine dehydrogenase [DPD] play the essential role in the activation and catabolism of the fluoropyrimidines used in cancer therapy. Its expression may influence the antitumor activity or toxicity of these drugs. We studied the expression levels of selected enzymes in colorectal tumors and adjacent normal mucosa. The analysis of TS, TP and DPD gene expression was performed using quantitative Real time PCR technique (Roche) in 15 (TS), 64 (TP) and 12 (DPD) of 64 colorectal cancer patients. The mean gene expression of TS, TP and DPD was found to be 3.29; 3.79 and 8.24 in tumors and 1.88; 3.80 and 19.69 in normal mucosa. The corresponding median gene expression was 1.87; 2.32 and 4.50 for tumors and 2.14; 2.63 and 11.64 for normal tissue. We did not find any significant differences in TS, TP and DPD gene expression between colorectal tumor and surrounding mucosa.     

Preoperative radiotherapy and concomitant capecitabine treatment induce thymidylate synthase and thymidine phosphorylase mRNAs in rectal carcinoma

This work is intended to study the effect of preoperative capecitabine and radiotherapy treatment on the levels of thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) mRNAs in rectal carcinoma. 55 patients with locally advanced rectal carcinoma (cT3-4, N0, M0 or cT2-4,N+, M0) were treated with capecitabine 825 mg/m2 twice a day and pelvic radiotherapy 1,8 Gy daily up to cumulative dose of 45 Gy, boosting up to 50,4 Gy. Patients underwent surgery 6th week after the completion of chemoradiotherapy. Biopsies of rectal carcinoma were taken before starting therapy and 14 days after its cesation. Biopsies were examined for TS, DPD and TP mRNA levels. CEA in serum was examined to monitor relapses. Both TP and TS mRNA increase two weeks after starting therapy (p<0,001). TP mRNA median levels were elevated 2,3x after starting therapy. Moreover responders exhibit 1,5x higher induction than non-responders both before and after starting therapy, but difference is significant before therapy only (p=0,017). Non-responders have most frequent TS induction. Complete remission was observed in 17% and substantial responses with microscopic residuum only in additional 19% of cases were achieved. The pathologic downstaging rate was 76%. Our data show that TS and TP mRNA are induced by preoperative chemoradiotherapy in both responders and nonresponders. TP induction is in accordance with the expected role of TP in the activation of capecitabine and the known promoting role of TP in tissue fibrosis frequently associated with tumor regression.     

Cyclin D1反义寡核苷酸对胃癌细胞化疗敏感性的影响

目的 研究Cyclin D1反义寡核苷酸（ASODN）对胃癌细胞SGC-7901和HS-746T化疗敏感性的影响,并探讨其内在机制。方法 在给予Cyclin D1 ASODN和Cyclin D1反义寡核苷酸转染细胞24h后,分别给予梯度浓度的5-氟尿嘧啶（5-FU）、氨甲喋呤（MTX）、顺铂（CDDP）,观察各组的量效反应,计算IC50。Cyclin D1 ASODN转染细胞后24h、48h时应用RT—PCR分别检测各组细胞中胸苷酸合酶（TS）、胸腺嘧啶磷酸化酶（TP）、二氢叶酸还原酶（DHFR）的表达情况。结果 Cyclin D1 ASODN转染增加了两种胃癌细胞对5-FU、MTX、CDDP的敏感性,ASODN＋化疗组对各化疗药物的lc50与对照组相比均有显著下降。RT—PCR显示Cyclin D1 ASODN转染后24h时Cyclin D1、TS、DHFR mRNA表达较对照组下降,而TP mRNA表达较对照组升高,在48h时各种酶mRNA表达的改变更加明显。结论 Cyclin D1 ASODN能提高胃癌细胞对多种化疗药物的敏感性,可能是由于影响了化疗药物代谢相关酶表达的改变所致。     

Significance of dihydropyrimidine dehydrogenase and thymidylate synthase mRNA expressions in hepatocellular carcinoma

Aim:  The significance of dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) gene expressions for the post-surgical prognosis of hepatocellular carcinoma (HCC) has not yet been determined. In the present study, we clarified the significance of DPD and TS gene expressions for the prognosis of HCC.
Methods:  Seventy-four patients, who underwent curative hepatic resection for primary HCC, were evaluated. The DPD and TS mRNA levels of the resected HCC specimens were evaluated using a microdissection technique and quantative real-time RT-PCR. The patients were categorized into high and low groups for each mRNA based on the median value. Various clinicopathological factors, including prognosis, and proliferation index using Ki-67 staining were evaluated in association with the DPD and TS mRNA expression levels.
Results:  The low DPD mRNA expression was related to younger age, advanced clinical stage, undifferentiated histology, and microscopic intrahepatic metastasis. The overall and recurrence-free survival were significantly lower in the low DPD group than in the high DPD group ( P  < 0.05). Furthermore, the proliferation index in the low DPD group was significantly higher than that in the high DPD group ( P  < 0.01). On the other hand, the high TS group showed a tendency of better prognosis than the low TS group, although it was not statistically significant.
Conclusions:  The low DPD mRNA expression is a significant poor prognostic factor. after curative resection of HCC.     

Thymidilate synthase expression predicts longer survival in patients with stage II colon cancer treated with 5-flurouracil independently of microsatellite instability

Background  

5-Fluorouracil (5-FU) is the most commonly used therapeutic agent for colon cancer treatment. Several studies have evaluated in patients with colon cancer, either the role of genes involved in the 5-FU pathway, such as thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) or the role of microsatellite instability (MSI) as prognostic or predictive markers for adjuvant chemotherapy efficacy, with discordant results. In this study we investigated the combined effect of TS, TP, DPD mRNA expression and MSI status in primary tumors of patients with colon cancer, all treated with 5-FU adjuvant therapy.     

Role of dihydropyrimidine dehydrogenase and thymidylate synthase expression in immunohistochemistry of intrahepatic cholangiocarcinoma

Aims: Dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) are key enzymes in the metabolism of 5‐fluorouracil and have been implicated as possible prognostic markers for cancer patients. However, the clinical roles of DPD and TS in intrahepatic cholangiocarcinoma (IHCC) have not been investigated. The aim of this study was to clarify the clinicopathological role of DPD and TS expressions in IHCC. Methods: Twenty‐nine patients who had undergone hepatic resection for IHCC were enrolled in this study. Expressions of DPD and TS in the resected IHCC specimens were examined using anti‐DPD or anti‐TS antibody. The patients were divided into positive and negative groups according to DPD/TS expressions: DPD‐positive group (n = 18) and DPD‐negative group (n = 11)/TS‐positive group (n = 14) and TS‐negative group (n = 15). Clinicopathological factors were compared between the two groups. Results: The overall survival rate was significantly lower in the DPD‐negative group than in the DPD‐positive group (1‐year 36.4% vs. 77.4%, 3‐year 18.2% vs. 43.0%; P < 0.05). The disease‐free survival rate in the DPD‐negative group tended to be lower than that in the DPD‐positive group. The overall survival rate or disease‐free survival rate did not appear to be associated with the TS‐expression status. The Ki‐67 labeling index in the DPD‐negative group was significantly higher than that in the DPD‐positive group (16.9 ± 3.2% vs.13.2 ± 3.3%; P < 0.05). Conclusions: The negative DPD expression was significantly associated with the enhanced tumor cell proliferation and poorer prognosis in patients with IHCC. DPD expression is a potential prognostic indicator for IHCC.