The inverse relationship between bladder and liver in 4-aminobiphenyl-induced DNA damage

Bladder cancer risk is significantly higher in men than in women. 4-Aminobiphenyl (ABP) is a major human bladder carcinogen from tobacco smoke and other sources. In mice, male bladder is more susceptible to ABP-induced carcinogenesis than female bladder, but ABP is more carcinogenic in the livers of female mice than of male mice. Here, we show that castration causes male mice to acquire female phenotype regarding susceptibility of bladder and liver to ABP. However, spaying has little impact on organ susceptibility to ABP. Liver UDP-glucuronosyltransferases (UGTs) are believed to protect liver against but sensitize bladder to ABP, as glucuronidation of ABP and its metabolites generally reduces their toxicity and promotes their elimination via urine, but the metabolites are labile in urine, delivering carcinogenic species to the bladder. Indeed, liver expression of ABP-metabolizing human UGT1A3 transgene in mice increases bladder susceptibility to ABP. However, ABP-specific liver UGT activity is significantly higher in wild-type female mice than in their male counterparts, and castration also significantly increases ABP-specific UGT activity in the liver. Taken together, our data suggest that androgen increases bladder susceptibility to ABP via liver, likely by modulating an ABP-metabolizing liver enzyme, but exclude UGT as an important mediator.     

Levels of the adducts of 4-aminobiphenyl to hemoglobin in control subjects and bladder carcinoma patients

We determined the hemoglobin adduct levels of one aromatic amine of cigarette smoke, 4-aminobiphenyl (4-ABP), in smoking controls and in patients with transitional cell bladder carcinoma. Covalently bound 4-ABP was measured by capillary gas-chromatography and negative-ion chemical ionization mass-spectrometry, using deuterated 4-ABP as internal standard. Smoking was quantified measuringthe urinary excretion of cotinine. Thirteen cases and controls were paired for urinary continine levels. Bladder carcinoma patients had slightly higher levels of 4-ABP hemoglobin adducts than controls (means ± S.D. were 103 ± 47 and 65 ± 44, respectively). This difference was significant using a t-test for paired samples (P = 0.04) and nonparametric Kruskal-Wallis rank analysis (P = 0.033).     

4-Aminobiphenyl-DNA adducts in laryngeal tissue and smoking habits: an immunohistochemical study

4-Aminobiphenyl (4-ABP)-DNA adducts and p53 overexpression were evaluated in laryngeal biopsies from 38 patients by immunohistochemical methods. Samples were categorized as tumors (n = 9), polyps (n = 28) or normal tissue (n = 1). 4-ABP-DNA adducts were evaluated with a quantitative immunoperoxidase method using monoclonal antibody 3C8 in both the lesion and adjacent tissue. Relative staining intensity data showed a log-normal distribution and values found in adjacent tissue from smokers were significantly higher (median: 173.5, geometric mean: 159.9) than those measured in adjacent tissue from non-smokers (median: 75.5, geometric mean: 7.40). Statistical significance was assessed both by non-parametric testing on raw data (P = 0.0007 on rank sum test) and by parametric testing on log-transformed data (P = 0.0002 on an unpaired t-test). Furthermore, relative staining intensity in the lesional tissue showed the same significant difference between smokers and non-smokers in patients affected by polyps, whereas no significant difference was detected in patients with laryngeal tumors. Overexpression of p53, also measured with an immunoperoxidase method, was observed in 44% of the malignant tumors and in 3.5% of the polyps. This work demonstrates that 4-ABP-DNA adducts can be evaluated in laryngeal tissue and are related to smoking exposure.      

Accelerated repair and reduced mutagenicity of oxidative DNA damage in human bladder cells expressing the E. coli FPG protein

Repair of some oxidized purines such as 8-oxo-7,8-dihydroguanine (8-oxoG) is inefficient in human cells in comparison to repair of other major endogenous lesions (e.g. uracil, abasic sites or oxidized pyrimidines). This is due to the poor catalytic properties of hOGG1, the major DNA glycosylase involved in 8-oxoG removal. The formamidopyrimidine DNA glycosylase (FPG) protein from E. coli is endowed with a potent 8-oxoG glycolytic activity coupled with a beta,delta-AP lyase. In this study, we have expressed FPG fused to the enhanced green fluorescent protein (EGFP) in human bladder cells to accelerate the repair of oxidative DNA damage. Cells expressing the fusion protein EGFP-FPG repaired 8-oxoG and AP sites at accelerated rates, in particular via the single-nucleotide insertion base excision repair (BER) pathway and were resistant to mutagenicity of the oxidizing carcinogen potassium bromate. FPG may stably protect human cells from some harmful effects of oxidative DNA damage.     

MicroRNA-143 functions as a tumor suppressor in human bladder cancer T24 cells

MicroRNA (miR)-143 and -145 were down-regulated in human bladder cancer T24 cells. The enforced expression of miR-143 induced growth-suppression in T24 cells through down-regulation of ERK5 and Akt expression at translational level, and chemically-modified synthetic miR-143 (miR-143/BP) exhibited a greater growth inhibitory effect than wild-type miR-143. In addition, the synthetic miR-143/BP induced apoptotic cell death in some of the transfected cells. Furthermore, co-treatment with the synthetic miR-143/BP and cisplatin showed the additive growth-suppressing effect on T24 cells. These findings suggest that the chemically-modified synthetic miR-143 functions as a tumor suppressor in T24 cells by targeting ERK5 and/or Akt.     

Prostaglandin receptors EP1-4 as a potential marker for clinical outcome in urothelial bladder cancer

Prostaglandins, especially prostaglandin E₂ (PGE₂), and COX-2 play an important role in carcinogenesis of many tumors including bladder cancer (BCA). The PGE₂ receptors EP1-4 regulate tumor cell growth, invasion and migration in different tumor entities but EP expression in BCA remains to be determined. In the present study we examined the expression of EP1-4 in non-muscle invasive bladder cancer (NMIBC), muscle invasive bladder cancer (MIBC) and normal urothelial tissue (NU) using immunohistochemistry. Nuclear and cytoplasmic EP1-4 expression was correlated with clinicopathological parameters and survival of BCA patients. EP1, EP2 and EP3 were significantly less expressed in the cytoplasm und nucleus of NMIBC and MIBC than in NU; EP4 cytoplasmic staining in MIBC was significantly higher compared to NU. The cytoplasmic staining was significantly more abundant in MIBC than in NMIBC in all investigated receptors except EP2. The level of EP staining in NMIBC was correlated with staging and grading, especially cytoplasmic EP1. Nuclear staining of EP1 was an independent predictor of BCA recurrence-free survival in NMIBC patients. EP receptors are dysregulated in BCA. The increase of EP1 may be used as prognostic parameter in NMIBC patients and its dysregulation could be targeted by specific EP1 inhibitors.     

CD40蛋白质在膀胱尿路上皮癌组织中的表达及其临床意义

 目的　研究CD40在膀胱尿路上皮癌的表达,探讨其与肿瘤分期、病理分级、细胞凋亡之间的相关性。方法　采用免疫组织化学技术检测20例膀胱癌旁组织及78例膀胱尿路上皮癌组织中CD40的表达状况,Hoechst法检测膀胱尿路上皮癌组织细胞凋亡情况,确定凋亡率。结果　CD40在20例膀胱癌旁组织中2例表达（10 %）,在78例膀胱尿路上皮癌组织中55例表达（70.5 %）,差异有统计学意义（P＜0.01）,CD40的表达与膀胱尿路上皮癌的临床分期、病理分级呈负相关。CD40阳性组细胞凋亡率为（12.60±0.38）%,阴性组细胞凋亡率为（6.77±0.53）%,差异有统计学意义（P＜0.01）,提示CD40可能诱导细胞凋亡。结论　CD40在膀胱尿路上皮癌组织的表达与肿瘤的临床分期、病理分级、细胞凋亡密切相关,可为膀胱尿路上皮癌的诊断、治疗及指导预后提供实验依据。     

Genetic alterations and DNA repair in human carcinogenesis

A causal association between genetic alterations and cancer is supported by extensive experimental and epidemiological data. Mutational inactivation of tumor suppressor genes and activation of oncogenes are associated with the development of a wide range of cancers. The link between mutagenesis and carcinogenesis is particularly evident for cancers induced by chemical exposures, which, in some cases, lead to characteristic patterns of mutations. These "genotoxic," direct-acting carcinogens form covalent adducts with DNA, which cause mutations during DNA replication. The link between mutagenesis and carcinogenesis is also supported by the observation that DNA repair defects are associated with an increased cancer risk. Normally, DNA repair mechanisms serve to suppress mutagenesis by correcting DNA damage before it can lead to heritable mutations. It has been postulated that mutagenesis plays a role in both the initiation phase and the progression phase of carcinogenesis, and that an essential step in the carcinogenic process is the development of a mutator state in which the normal cellular processes that suppress mutagenesis become compromised. Given the link between mutations and cancer, attempts have been made to use the mutational profile of cancer cells as an indicator of the causative agent. While this may be a valid approach in some cases, it is complicated by the role of endogenous processes in promoting mutagenesis. In addition, many important carcinogenic agents may enhance mutagenesis indirectly through suppression of DNA repair functions or stimulation of inappropriate cell proliferation. Epigenetic phenomena may also suppress gene expression without causing overt changes in DNA sequence.     

C-myc蛋白和增殖细胞核抗原在人膀胱癌组织中表达的意义

应用增殖细胞核抗原（PCNA）和C－myc单克隆抗体，以免疫组织化学方法检测正常膀胱组织和膀胱癌组织中Cmyc蛋白和PCNA的表达水平。结果表明：5例正常膀胱组织中未发现C－myc和PCNA阳性表达，阳性表达的C－myc和PCNA均定位于肿瘤的细胞核内。58例膀胱癌中C－myc和PCNA蛋白阳性表达分别为43．1％和62．1％，并且C－myc和PCNA阳性表达率与膀胱癌的病理分级、临床分期和患者术后生存率相关。提示C－myc和PCNA阳性表达与膀胱癌发生发展相关，并有可能成为评价膀胱癌预后的指标之一。     

Stromal modulation of bladder cancer-initiating cells in a subcutaneous tumor model

The development of new cancer therapeutics would benefit from incorporating efficient tumor models that mimic human disease. We have developed a subcutaneous bladder tumor regeneration system that recapitulates primary human bladder tumor architecture by recombining benign human fetal bladder stromal cells with SW780 bladder carcinoma cells. As a first step, SW780 cells were seeded in ultra low attachment cultures in order to select for sphere-forming cells, the putative cancer stem cell (CSC) phenotype. Spheroids were combined with primary human fetal stromal cells or vehicle control and injected subcutaneously with Matrigel into NSG mice. SW780 bladder tumors that formed in the presence of stroma showed accelerated growth, muscle invasion, epithelial to mesenchymal transition (EMT), decreased differentiation, and greater activation of growth pathways compared to tumors formed in the absence of fetal stroma. Tumors grown with stroma also demonstrated a greater similarity to typical malignant bladder architecture, including the formation of papillary structures. In an effort to determine if cancer cells from primary tumors could form similar structures in vivo using this recombinatorial approach, putative CSCs, sorted based on the CD44⁺CD49f⁺ antigenic profile, were collected and recombined with fetal bladder stromal cells and Matrigel prior to subcutaneous implantation. Retrieved grafts contained tumors that exhibited the same structure as the original primary human tumor. Primary bladder tumor regeneration using human fetal bladder stroma may help elucidate the influences of stroma on tumor growth and development, as well as provide an efficient and accessible system for therapeutic testing.     

BCL-2, TP53 and BAX protein expression in superficial urothelial bladder carcinoma

Whether TP53, BCL-2 and BAX expressions add independent prognostic information in patients with Ta/T1bladder urothelial carcinoma remains unclear. TP53 overexpression correlated with high tumor grade (p = 0.004), WHO grading categories (0.045), BAX expression (p = 0.043) and pathologic stage (p = 0.05). BCL-2 immunostaining was inverse associated with tumor grade (p = 0.008). Lack of BAX expression was related to reduced patient’s survival (p = 0.028). Mortality was higher in patients with BCL-2+/TP53+ (p = 0.023) or TP53+/BAX− (p = 0.027) phenotype. BAX and pathologic stage were independent predictors of progression-free and overall survival, respectively. Therefore, BAX expression might be relevant in patient’s prognosis.     

吲哚胺2,3-双加氧酶、c-myc在膀胱尿路上皮癌中的表达及其意义

目的 探讨吲哚胺2,3-双加氧酶（IDO）、c-myc在膀胱尿路上皮癌中的表达及其临床意义.方法 采用荧光定量聚合酶链反应（PCR）检测新鲜肿瘤及黏膜标本各20例IDO mRNA表达,采用SP法检测肿瘤石蜡标本84例及黏膜22例IDO、c-myc蛋白的表达,分析二者与临床病理特征的关系.结果 在膀胱尿路上皮癌组织中,IDO、c-myc蛋白表达强度与患者年龄、性别无关.在浸润型膀胱尿路上皮癌组织中IDO蛋白表达高于非浸润型（x2=5.600,P=0.018）,随着组织分级及国际抗癌联盟（UICC）分期增高,IDO蛋白阳性表达率增高（x2=20.268,P=0.000;x2=12.075,P=0.007）.c-myc蛋白在正常膀胱组织中无阳性表达,在膀胱尿路上皮癌组织中44例（52.4％）表达阳性,二者阳性表达率差异有统计学意义（x2=10.733,P=0.001）;c-myc蛋白表达强度与组织学分类、组织分级及UICC分期无关.在膀胱尿路上皮癌组织中IDO蛋白表达强度与c-myc蛋白表达强度呈正相关（r=0.205,P=0.047）,与组织学分类、组织分级及UICC分期呈正相关（r=0.258,P=0.018;r=0.491,P=0.000;r=0.365,P=0.001）.IDO mRNA在膀胱尿路上皮癌组织中的表达（7.696 1±1.745 2）明显高于正常膀胱组织（6.397 0±1.205 1）（t=2.367,P=0.023）.Ta～T1期膀胱尿路上皮癌组织中IDO mRNA的平均表达水平为6.803 4±1.567 5,明显低于T2～T4期的9.183 8±0.690 3（t=4.955,P=0.000）;IDO mRNA在Ⅰ、Ⅱ、Ⅲ级膀胱尿路上皮癌组织中的平均表达水平分别为7.058 7±1.771 5、7.934 2±1.530 5、9.290 7±0.574 5,随着分级增高而增高,差异有统计学意义（t=2.729,P=0.011）.结论 IDO表达与膀胱尿路上皮癌预后不良相关,c-myc表达强度与膀胱尿路上皮癌病变进展无关,但可能与膀胱尿路上皮癌病变发生有关.IDO可能成为膀胱尿路上皮癌预后的预测因子,IDO、c-myc有可能成为肿瘤化疗的一个分子靶向目标.     

Correlation of human bladder tumor recurrence with changes in clonogenicity of urothelial cells

Over a 2-year period 340 cystoscopies were performed on 174 patients (126 men and 48 women) followed up for previously treated transitional cell tumor of the bladder or new cases suspected of having bladder tumor. Bladder washings taken at cystoscopy in 66% yielded cells for clonogenic assay. Patients with transitional cell tumors had an average clonogenic index (CI) of 14 (+/- 5) colonies per 10(5) viable urothelial cells, whereas previously tumorous patients with tumor-free bladders had an average CI of 6 +/- 1 colonies (P less than 0.001, Student's t test). Patients with hematuria but no bladder tumor had an average CI of 8 (not significant). In serial examinations with consecutive successful clonogenic assay, 11 of 16 patients remaining tumor-free had constant or falling CI whereas 9 of 12 patients with recurrent tumor had rising CI values (Fisher; P less than 0.025). Changes in the clonogenic index of cells taken from bladder washings paralleled the changes in tumor status at cystoscopy and might have predictive value in this disease.     

Antitumour 2-(4-aminophenyl)benzothiazoles generate DNA adducts in sensitive tumour cells in vitro and in vivo

2-(4-Aminophenyl)benzothiazoles represent a potent and highly selective class of antitumour agent. In vitro, sensitive carcinoma cells deplete 2-(4-aminophenyl)benzothiazoles from nutrient media; cytochrome P450 1A1 activity, critical for execution of antitumour activity, and protein expression are powerfully induced. 2-(4-Amino-3-methylphenyl)benzothiazole-derived covalent binding to cytochrome P450 1A1 is reduced by glutathione, suggesting 1A1-dependent production of a reactive electrophilic species. In vitro, 2-(4-aminophenyl)benzothiazole-generated DNA adducts form in sensitive tumour cells only. At concentrations >100 nM, adducts were detected in DNA of MCF-7 cells treated with 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203). 5F 203 (1 microM) led to the formation of one major and a number of minor adducts. However, treatment of cells with 10 microM 5F 203 resulted in the emergence of a new dominant adduct. Adducts accumulated steadily within DNA of MCF-7 cells exposed to 1 microM 5F 203 between 2 and 24 h. Concentrations of the lysylamide prodrug of 5F 203 (Phortress) > or = 100 nM generated adducts in the DNA of sensitive MCF-7 and IGROV-1 ovarian cells. At 1 microM, one major Phortress-derived DNA adduct was detected in these two sensitive phenotypes; 10 microM Phortress led to the emergence of an additional major adduct detected in the DNA of MCF-7 cells. Inherently resistant MDA-MB-435 breast carcinoma cells incurred no DNA damage upon exposure to Phortress (< or = 10 microM, 24 h). In vivo, DNA adducts accumulated within sensitive ovarian IGROV-1 and breast MCF-7 xenografts 24 h after treatment of mice with Phortress (20 mg kg(-1)). Moreover, Phortress-derived DNA adduct generation distinguished sensitive MCF-7 tumours from inherently resistant MDA-MB-435 xenografts implanted in opposite flanks of the same mouse.     

Genomic alterations in tumor tissue and ctDNA from Chinese pancreatic cancer patients

Though the genomic feature of pancreatic cancer has been comprehensively studied in western patients, the genetic feature of Chinese patients is poorly clarified. In this study, a total of 225 pancreatic cancer patients were enrolled, mainly pancreatic ductal adenocarcinoma (PDAC, 97.33%). 140 patients (62.22%) provided sufficient tumor tissues for genomic analysis, and the rest (37.78%) were provided serum instead. Utilizing target next-generation sequencing (NGS), we analyzed genomic alterations of 618 selected genes. Corresponding data in the TCGA database were also analyzed here. In total, 26 (11.61%) patients had pathogenic or likely pathogenic germline variants, mainly (84.62%) involved genes in the DNA damage repair (DDR) pathway. The mean and median counts of somatic alterations per sample were 6.28 and 5, respectively. The most frequently mutated genes in our cohort were KRAS, TP53, CDKN2A, SMAD4, FBXW7 and ARID1A, revealing a significantly different prevalence of genes including KRAS, CDKN2A, ARID1A, NOTCH1, ARID1B than the corresponding data in the TCGA database. 39.11% of patients were identified with actionable alteration and the ratio was not significantly different between tissue and serum samples. 22.67% of patients harbored DDR gene alterations, which were associated with a higher tumor mutation burden. We also found that all the DDR alterations were not correlated with the overall survival and immune and stroma score, but the changes in NK cells and follicular T cells were identified in samples with DDR changes according to TCGA database. In summary, we identified a distinct genomic feature of Chinese pancreatic cancer patients by comparing with the data in TCGA database, and suggested the role for genetic testing using tissue or ctDNA samples in decision-making process. DDR alterations were associated with a higher tumor mutation burden and the significantly higher counts of NK cells in DDR altered samples may raise the attention in future related drugs development.     

Lack of mutagenicity of acrolein-induced DNA adducts in mouse and human cells

Acrolein is an endogenous metabolite and a ubiquitous environmental pollutant. Recently, it has been suggested that acrolein is a major etiologic agent for tobacco smoking-related lung cancer. Despite the known DNA-damaging effects of acrolein, its mutagenicity to mammalian cells remains uncertain. We have investigated acrolein-induced DNA damage in relation to mutagenesis, with special focus on DNA repair, in mouse and human cells. We mapped the formation of acrolein-induced DNA adducts and the kinetics of repair of the induced lesions in the cII transgene, the mutational target, in acrolein-treated transgenic mouse fibroblasts. Acrolein-DNA adducts were formed preferentially at specific nucleotide positions, mainly at G:C base pairs, along the cII transgene. The induced acrolein-DNA adducts were moderately resistant to DNA repair. Quantification of cII mutant frequency in acrolein-treated cells, however, revealed that acrolein was not mutagenic to these cells at doses sufficient to produce DNA adducts. Determination of supF mutant frequency in DNA repair-proficient and DNA repair-deficient human fibroblasts transfected with acrolein-treated plasmids confirmed a lack of acrolein mutagenicity. Because CpG methylation may intensify acrolein-DNA adduction, we examined whether the extent of CpG methylation in the supF gene can determine acrolein-induced mutagenesis in human cells. Enhancement of acrolein-DNA adduction by methylating CpGs in the supF sequence did not elicit a mutagenic response in human fibroblasts, however. We conclude that acrolein is not mutagenic to mouse and human fibroblasts, regardless of DNA repair capacity or methylation status of CpGs, possibly because of a highly accurate replication bypass of the induced lesions.     

Effects of curcumin on bladder cancer cells and development of urothelial tumors in a rat bladder carcinogenesis model

Curcumin, a well-known dietary pigment derived from Curcuma longa, inhibited growth of several types of malignant cells both in vivo and in vitro. Its effects on cell proliferation and the induction of apoptosis in human bladder cancer cell lines and intravesical activity in a rat bladder tumor model were studied. Exposure of human bladder cancer cells to curcumin resulted in the induction of apoptotic cell death and caused cells to arrest in the G2/M phase. The anti-apoptotic Bcl-2 and Survivin protein was downregulated by the curcumin treatment together with enhancement of the Bax and p53 expression. The inhibitory activities of curcumin were stronger than those of cisplatin and could not be prevented by catalase pretreatment in T24 cells. Clonal assay indicated large-dose and short-term curcumin was lethal to bladder cancer cells. Moreover, the in vivo study revealed curcumin did induce apoptosis in situ, inhibit and slow the development of bladder cancer. These observations suggest that curcumin could prove an effective chemopreventive and chemotherapy agent for bladder cancer.     

First- and second-line therapy for metastatic urothelial carcinoma of the bladder

Urothelial cancer of the bladder is the 4th most common malignancy in American men and the 9th most common in women. Although it is a chemosensitive disease, advanced bladder cancer seems to have reached a plateau with regard to median survival of patients. Standard first-line therapy remains gemcitabine plus cisplatin (gc) or methotrexate, vinblastine, doxorubicin, and cisplatin (mvac). In patients deemed unfit to receive cisplatin, gemcitabine plus carboplatin or gemcitabine plus paclitaxel can be considered. To date, no standard therapy has been established for patients who recur or are refractory to first-line therapy. Second-line vinflunine, by way of superiority over best supportive care, has shown promise in a phase iii trial. Cisplatin-based therapy (mvac or gc) can also be offered to patients previously treated with cisplatin, especially if they responded previously and are considered platinum-sensitive. Novel targeted therapies are sorely needed to further improve the delivery and efficacy of chemotherapy.     

BCG及IL-2激活膀胱癌患者PBMC及TIL细胞的抗癌活性比较

 用Whitesides法从15例膀胱移行细胞癌患者外周血及癌手术标本中获得的外周血单个核细胞（PBMC）及肿瘤浸润淋巴细胞（TIL）,分别用活BCG、死BCG及IL－2刺激培养,计算细胞增殖倍数并测定其抗癌活性。结果,死BCG对细胞并无激活作用;IL－2对细胞的诱导增殖作用强于活BCG,而其激活这两种细胞的抗癌活性低于活BCG激活的抗癌活性。BCG对免疫受抑制的PBMC及YIL细胞的激活作用可能是BCG抗肿瘤重要作用机理之一。并为BCG的进一步临床免疫治疗奠定理论基础。     

胃癌组织与外周血淋巴细胞ERCC1表达的相关性研究

目的 探讨切除修复交叉互补基因1（ERCC1）在胃癌的癌组织和外周血淋巴细胞（PBLC）中表达的相关性及其与临床病理特征的关系。方法 采用免疫组化法检测53例胃癌术后癌组织和PBLC中ERCC1的表达,另取20例胃肠道良性疾病和正常人的PBLC作为对照。结果 胃癌的癌组织、PBLC和对照组的PBLC 中ERCC1的阳性表达率分别为67.9％、56.6％和10.0％,胃癌的PBLC中ERCC1的阳性表达率显著高于对照组（P＜0.05）。在胃癌的癌组织和PBLC中,ERCC1表达与年龄、性别、病理类型、临床分期、T分期、淋巴结转移和分化程度均无关。胃癌的癌组织与PBLC中ERCC1的表达呈正相关（r=0.475,P=0.000）。结论 通过检测胃癌的PBLC中ERCC1表达可以间接反映癌组织中ERCC1的表达状况。