High cytoplasm HABP1 expression as a predictor of poor survival and late tumor stage in pancreatic ductal adenocarcinoma patients

BackgroundHyaluronan-binding protein 1 (HABP1) overexpression has been confirmed in different malignancies and found to be strongly associated with tumor development and progression. The aim of the present study was to explore the impact of HABP1 in pancreatic ductal adenocarcinoma (PDAC) patients.MethodHABP1 expression was evaluated in 89 PDAC specimens.ResultsThe expression of HABP1 was significantly higher in tumor tissues than that in adjacent normal tissues. High nucleus HABP1 expression and high cytoplasm HABP1 expression were both detected in PDAC tissues. Overall survival analysis by optical density showed that the mean survival was similar between patients with low and high optical density values of HABP1 expression (P = 0.312). The similar result was also found between patients with low-moderate or high nucleus HABP1 expression (P = 0.275). However, the mean survival was significantly poorer in patients with cytoplasm HABP1 overexpression (P < 0.001). High cytoplasm HABP1 expression was strongly correlated with late tumor stages, arterial involvement, lymph node metastasis and carbohydrate antigen 19-9 levels.ConclusionHigh cytoplasm HABP1 expression may prove to be a predictor of poor survival and late tumor stage in PDAC patients. HABP1 could serve as a promising biomarker to identify subsets of PDAC patients with high malignant clinical behavior.     

Molecular signatures of mRNAs and miRNAs as prognostic biomarkers in pancreatobiliary and intestinal types of periampullary adenocarcinomas

Periampullary adenocarcinomas include four anatomical sites of origin (the pancreatic duct, bile duct, ampulla and duodenum) and most of them fall into two histological subgroups (pancreatobiliary and intestinal). Determining the exact origin of the tumor is sometimes difficult, due to overlapping histopathological characteristics. The prognosis depends on the histological subtype, as well as on the anatomical site of origin, the former being the more important. The molecular basis for these differences in prognosis is poorly understood. Whole‐genome analyses were used to investigate the association between molecular tumor profiles, pathogenesis and prognosis. A total of 85 periampullary adenocarcinomas were characterized by mRNA and miRNA expressions profiling. Molecular profiles of the tumors from the different anatomical sites of origin as well as of the different histological subtypes were compared. Differentially expressed mRNAs and miRNAs between the two histopathological subtypes were linked to specific molecular pathways. Six miRNA families were downregulated and four were upregulated in the pancreatobiliary type as compared to the intestinal type (P < 0.05). miRNAs and mRNAs associated with improved overall and recurrence free survival for the two histopathological subtypes were identified. For the pancreatobiliary type the genes ATM, PTEN, RB1 and the miRNAs miR‐592 and miR‐497, and for the intestinal type the genes PDPK1, PIK3R2, G6PC and the miRNAs miR‐127‐3p, miR‐377* were linked to enriched pathways and identified as prognostic markers. The molecular signatures identified may in the future guide the clinicians in the therapeutic decision making to an individualized treatment, if confirmed in other larger datasets.     

Disposition in mice of 7-hydroxystaurosporine,a protein kinase inhibitor with antitumor activity

UCN-01, a hydroxylated derivative of staurosporine, was selected for study because of its promising antitumor activity. For mice dosed intravenously, subcutaneously, or by oral gavage with this compound, the maximum tolerated doses (MTD) were 20, 10, and >100 mg/kg, respectively. UCN-01 was stable in mouse and dog plasma, but in human plasma it was converted to a metabolite in a process not inhibited by standard protease and esterase inhibitors. Following n intravenous dose of 10 mg/kg UCN-01, the half-lives for the initial (t _1/2) and terminal (t _1/2) exponential phases of elimination were 10 and 85 min, respectively; the area under the plasma concentration-time curve (AUC value) was 117 g min ml^–1. In mice dosed by oral gavage with 10 mg/kg, the calculated value for the half-life of the elimination phase was 150 min. The AUC value was 15 g min ml^–1, giving a value for bioavailability of 13%. After subcutaneous dosing with 10 mg/kg, the calculated values for half-lives for the distribution and elimination phases were 23 and 130 min, respectively; the AUC value was 113 g min ml^–1. Since this value is equivalent to that obtained for intravenous dosing, administration of UCN-01 by the subcutaneous route may be an alternative to intravenous dosing in preclinical and clinical trials.This work was supported by contract NO1-CM-27710 (National Cancer Institute, National Institutes of Health, Department of Health and Human Services)     

Diagnostic and prognostic potential of the novel biomarker nuclear cap binding protein subunit 2 (NCBP2) in colon adenocarcinoma

BackgroundColon adenocarcinoma (COAD) is an incurable malignancy and the third most common tumor worldwide. Advances in biomarkers screening have greatly contributed to explore the new diagnostic and prognostic biomarkers for the early detection and prognostic of COAD. However, the heterogeneity-specific nature of COAD in patients of different cancer stages, different races, genders and age are still the major challenge to clinical treatment.MethodsGene expression, copy number (CN), and dependency score (DS) data were obtained from the Cancer Cell Line Encyclopedia (CCLE), and linear regression analyses were performed using R language. We conducted receiver operating characteristic (ROC) curve analysis and compared the area under the ROC curve area under the curve (AUC) values to evaluate the sensitivity and specificity of nuclear cap binding protein subunit 2 (NCBP2) for the diagnosis of COAD in The Cancer Genome Atlas (TCGA) database. Survival analysis was performed in the distinct NCBP2 expression groups. In vitro experiments and bioinformatics analysis were used to investigate the molecular mechanisms of NCBP2 in COAD and its biological roles. A Connectivity Map (Cmap) was used to identify potential small molecule targeted drugs for NCBP2 in COAD.ResultsThrough the linear regression analysis of DS, CN, and gene expression, we determined that NCBP2 met our criteria. The mean AUC of the ROC curve of NCBP2 was 0.940±0.050. Survival analysis showed that high NCBP2 expression was associated with a worse prognosis [hazard ratio (HR) =1.98, P<0.007]. NCBP2 knockdown inhibited COAD cell proliferation and caused G0/G1 phase arrest in COAD cells.ConclusionsNCBP2 was the novel diagnostic and prognostic biomarker of in COAD. Our research had implications for the treatment of colon cancer.     

Serum protein binding of lerisetron, a novel specific 5HT3 antagonist, in patients with cancer

The aim of this study was, (1) to characterize the serum protein binding of lerisetron, a new 5-hydroxytryptamine (5-HT₃) receptor antagonist under investigation as an antiemetic agent, and (2) to measure the percentage of unbound lerisetron in cancer patients. The binding parameters were determined in human serum albumin (HSA), α₁-acid glycoprotein (AAG) and in pooled serum from six healthy volunteers. Concentrations of lerisetron ranging from 50 ng/ml to 2 μg/ml were used. The serum protein binding of ¹⁴C-lerisetron (2 μg/ml) was determined by ultrafiltration in three groups of individuals. Group I comprised healthy subjects (n = 11), group II comprised cancer patients undergoing radiotherapy (n = 9), and group III comprised cancer patients receiving chemotherapy (n = 18). The unbound concentration of lerisetron was measured in all samples by liquid scintillation counting. Concentrations of both AAG and HSA were also measured in all serum samples. The drug was extensively bound in pooled serum, involving a nonsaturated process. In HSA, lerisetron was also highly bound (4.04 ± 0.8% unbound) and the protein binding was essentially unchanged within the studied concentration range of lerisetron. The extent of binding to AAG was high but significantly lower than in serum and in HSA and was also independent of lerisetron concentration. The unbound lerisetron was significantly decreased in group II cancer patients when compared with group I subjects (2.38 ± 0.64% vs 3.70 ± 0.70%; P < 0.001). No significant changes in lerisetron binding were observed in group III patients. HSA was diminished in both groups of patients and AAG was only significantly increased in group II. Unbound lerisetron was correlated with AAG in group II and with HSA in group III. Received: 8 August 1997 / Accepted: 27 February 1998     

Loss of programmed cell death 4 expression marks adenoma-carcinoma transition, correlates inversely with phosphorylated protein kinase B, and is an independent prognostic factor in resected colorectal cancer

BACKGROUND: Programmed cell death 4 (Pdcd4) inhibits malignant transformation, and initial studies of Pdcd4 suggested the regulation of Pdcd4 localization by protein kinase B (Akt). However, supporting patient tissue data are missing, and the diagnostic/prognostic potential of Pdcd4 rarely has been studied. The objectives of the current were 1) to determine Pdcd4 as a diagnostic marker in the adenoma-carcinoma sequence, 2) to support phosphorylated Akt (pAkt)-mediated Pdcd4 regulation in vivo, and 3) to obtain the first prognostic evidence of Pdcd4 in colorectal cancer. METHODS: Tumor samples and normal tissues from 71 patients with colorectal cancer who were followed prospectively (median follow-up, 36 months) and 42 adenomas were analyzed for Pdcd4, Akt, and pAkt in immunohistochemical and Western blot analyses. RESULTS: A significant reduction in Pdcd4 was observed between normal mucosa and adenomas and between adenomas and tumor samples (P < .01 and P < .01, respectively). Normal mucosa demonstrated strong nuclear Pdcd4, which was reduced significantly in adenomas (P < .01) and almost was lost in tumors (P < .01). pAkt was correlated inversely with Pdcd4 and with the transition of Pdcd4 from nucleus to cytoplasm (P < .01). Kaplan-Meier analysis (using the Mantel-Cox log-rank test) indicated a significant correlation between the loss of total and nuclear Pdcd4 in tumors and overall survival (P < .05 and P < .02, respectively) and disease-specific survival (P < .01 and P < .01, respectively). In multivariate analysis, loss of total or nuclear Pdcd4 was an independent predictor of disease-specific or overall survival. CONCLUSIONS: To the authors' knowledge, this is the first study to demonstrate an independent prognostic impact of Pdcd4 and its expression pattern in colorectal cancer. Data from this study support the regulation of Pdcd4 localization by pAkt in vivo. Pdcd4 immunohistochemistry may be useful as a supportive diagnostic tool for the transition between normal, adenoma, and tumor tissues.     

CDCA7通过与MCM3相互作用介导胰腺癌细胞增殖、侵袭及迁移

目的:探讨细胞分裂周期相关蛋白7(cell division cycle-associated protein 7,CDCA7)对人胰腺癌细胞增殖、侵袭及迁移能力的影响,及其可能的作用机制.方法:利用癌症基因组图谱(The Cancer Genome Atlas,TCGA)和基因表达谱数据动态分析(Gene Expre...     

The tumor suppressing effects of QKI-5 in prostate cancer: A novel diagnostic and prognostic protein

In recent years, the RNA-binding protein quaking 5 (QKI-5) has been recognized as a novel tumor suppressor in many cancers. To date, no studies have examined the role of QKI-5 in prostate cancer. The present study was designed to elucidate the correlation of QKI-5 expression with the clinical pathological features and prognosis of prostate cancer. In an overwhelming majority of the 184 cases of prostate cancer samples analyzed, the QKI-5 expression was significantly decreased, which was largely due to the high promoter methylation levels. Using lentiviral vectors, we established two stable prostate cancer cell lines with altered QKI-5 expression, including a QKI-5 overexpressing PC3 cell line and a DU145 cell line with knocked-down QKI-5 expression. The effects of the lentiviral-mediated QKI-5 knockdown on the PC3 cells and DU145 cells were assessed by cell growth curves, flow cytometry (FCM), and an invasion assay. The PC3 cells were transplanted into nude mice, and then, the tumor growth curves and TUNEL staining were determined. These results demonstrated that QKI-5 was highly expressed in benign prostatic hyperplasia (BPH) tissues but not in carcinomatous tissues and that QKI-5 effectively inhibited prostate cancer cell proliferation in vitro and in vivo. In addition, the decrease in QKI-5 expression was closely correlated with the prostate cancer Gleason score, poor differentiation, degree of invasion, lymph node metastasis, distant metastasis, TNM grading, and poor survival. These results indicate that the QKI-5 expression may be a novel, independent factor in the prognosis of prostate cancer patients.     

LINC00857 promotes cell proliferation and migration in colorectal cancer by interacting with YTHDC1 and stabilizing SLC7A5

Colorectal cancer (CRC) is one of the most lethal malignances in humans. Hence, it is of great significance to identify regulatory molecules in CRC progression. Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) are involved in cancer malignancy. It has been reported that long intergenic non-protein coding RNA 857 (LINC00857) acts as a vital oncogene in many types of cancer by promoting cell proliferation and migration. However, the role of LINC00857 in CRC remains unclear. In the present study, LINC00857 was upregulated in CRC tissue samples and cells. Next, in vitro loss-of-function experiments demonstrated that LINC00857 knockdown suppressed CRC cell viability, proliferation and migration, as well as epithelial-mesenchymal transition and increased cell apoptosis. Mechanistically, LINC00857 abundantly interacted with the RNA-binding protein YTH domain containing 1 (YTHDC1). YTHDC1 ultimately combined with solute carrier family 7 member 5 (SLC7A5) and increased SLC7A5 mRNA stability. Finally, a series of rescue experiments indicated that LINC00857 promoted the proliferation and migration of CRC cells by regulating mRNA stability. Thus, the present findings illustrated that LINC00857 functions as an oncogene in CRC cells via the YTHDC1/SLC7A5 axis.     

Chemotherapy in elderly patients with pancreatic cancer: Efficacy,feasibility and future perspectives

By 2030 70% of newly diagnosed pancreatic ductal adenocarcinoma (PDAC) will occur in older adults. Elderly patients, defined by the World Health Organization (WHO) as people older than 65 years, represent a heterogeneous group with different biological and functional characteristics that need personalized anticancer treatments. Since older patients are under-represented in randomized phase III trials, their management is mostly extrapolated from studies performed in younger patients, without robust evidence-based recommendations. However, data from retrospective studies and case-control series show that elderly may benefit from chemotherapy in both the adjuvant and advanced disease settings. Although with discordant results, gemcitabine-based treatment and dose-adapted fluorouracil combination regimens seem to be effective and well tolerated in this subset of patients.A proper balance of potential treatment benefits and side effects represent the crucial point for managing elderly patients with PDAC. Therefore an appropriate patient selection is essential to maximize the therapeutic benefit in the older population: randomized studies aiming to better standardizing fitness parameters and implementing the routine use of comprehensive geriatric assessments are strongly warranted. In this light, the detection of molecular prognostic markers able to detect patients who may benefit more from oncological treatments should be a primary endpoint of age-focused clinical trials. Altogether, the field of geriatric oncology will expand in the next years, and the clinical management of elderly patients affected by PDAC will become a major public health issue.     

Phase I study of PKC412 (N-benzoyl-staurosporine), a novel oral protein kinase C inhibitor, combined with gemcitabine and cisplatin in patients with non-small-cell lung cancer.

BACKGROUND: PKC412 (N-benzoyl-staurosporine), an oral inhibitor of protein kinase C, is capable of cell cycle inhibition and is endowed with anti-angiogenic properties. This dose-finding phase I study was designed to establish the maximum tolerated dose (MTD) of PKC412 when combined with cisplatin-gemcitabine. PATIENTS AND METHODS: Escalating doses of PKC412 were given every day of a 4 week cycle with cisplatin 100 mg/m2 on day 2 and gemcitabine 1000 mg/m2 on days 1, 8 and 15 in patients with non-small-cell lung cancer. Dose escalation was based on a modified continuous reassessment method. RESULTS: Twenty-three patients, assigned to four cohorts receiving PKC412 at a dose ranging from 25 to 150 mg/day were evaluable. Grade 3 diarrhea occurring in 3/4 patients at cycle 1 led us to define 150 mg/day as the MTD. The MTD based on multiple cycles was redefined as 100 mg/day, since prolonged grade 2-3 nausea/vomiting leading to treatment discontinuation occurred in 3/7 patients after repeated cycles. The next lower dose tested of 50 mg/day was therefore considered as the recommended dose for phase II trials. Among 33 cycles in eight patients, toxicity consisted of grade 1-2 diarrhea (12.5%) and asthenia (50%) with only one patient experiencing grade 3 headache at this dose level. A partial response was observed in three patients. CONCLUSIONS: The results of the present study indicate that PKC412 at a dose of 50 mg/day can be safely added to cisplatin and gemcitabine in patients with advanced non-small-cell lung cancer.     

基质金属蛋白酶9、基质金属蛋白酶2、迁移诱导蛋白7和细丝蛋白A在结肠癌中的表达及其预后意义

目的:探讨基质金属蛋白酶9（MMP-9）、基质金属蛋白酶2（MMP-2）、迁移诱导蛋白7（MIG-7）、细丝蛋白A（FLNa）在结肠癌组织中的表达及其对预后的影响。方法:收集2013年1月至2015年12月南京医科大学附属淮安市第一人民医院899例结肠癌患者手术切除的肿瘤标本及其对应的癌旁正常组织。采用酶联免疫吸附试验...     

Identification of potential prognostic biomarkers in patients with untreated, advanced pancreatic cancer from a phase 3 trial (Cancer and Leukemia Group B 80303)

BACKGROUND:

Patients with advanced stage adenocarcinoma of the pancreas have a poor prognosis. The identification of prognostic and/or predictive biomarkers may help stratify patients so that therapy can be individualized.

METHODS:

Serum samples from patients enrolled in the Cancer and Leukemia Group B 80303 phase 3 trial, “Randomized Study of Gemcitabine With Versus Without Bevacizumab in Patients With Locally Advanced or Metastatic Adenocarcinoma of the Pancreas” were used to discover novel biomarkers. For the discovery phase, 40 sera were selected based on length of survival and type of therapy, and subjected to liquid chromatography coupled to tandem mass spectrometry analysis (LC‐MS‐MS). The top features (proteins) were then further selected for validation by enzyme‐linked immunosorbent assay (ELISA).

RESULTS:

Quantification by nano–LC‐MS‐MS resulted in 1452 peptides mapping to 156 proteins across all 40 samples, 92 of which had 2 or more peptides. After curation of the data, the authors selected 1 putative prognostic protein, alpha 1‐antichymotrypsin (AACT), and 2 putative predictive proteins, histidine‐rich glycoprotein (HRG) and complement factor H (CFH), for validation by ELISA. AACT was found to be negatively correlated with overall survival (τ = ?0.30 [?0.38, ?0.22]; P < .00001). There was no evidence for interaction with bevacizumab and HRG, but there was some evidence for a weak positive correlation of HRG with overall survival (τ = 0.11 [0.03, 0.19]; P < .01). CFH was found to be neither a predictive nor a prognostic factor for overall survival.

CONCLUSIONS:

AACT may be a useful prognostic marker in patients with advanced stage pancreatic carcinoma, although additional validation studies are needed. Cancer 2011;. © 2011 American Cancer Society.     

Adenosine 3′,5′-monophosphate protein kinase isoenzyme distribution in lymphocytes from normal individuals and patients with chronic lymphocytic leukaemia

Two major isoenzymic forms of adenosine 3′,5′-monophosphate (cyclic AMP)-dependent protein kinase were resolved by DEAE cellulose chromatography of cytosols of normal human lymphocytes and of abnormal (colchicine ultrasensitive) lymphocytes from patients with chronic lymphocytic leukaemia (CLL). With only one exception the activity of type I protein kinase exceeded that of type II in normal lymphocytes, whilst in CLL the activity of the type II isoenzyme exceeded that of the type I. The total activity of protein kinase was approximately the same in normal and CLL lymphocytes. This difference in isoenzyme distribution may reflect the immaturity of CLL lymphocytes.     

NapsinA、TTF-1、CK5/6、CK7、P63在非小细胞肺癌支气管镜活检标本中的表达及意义

目的 检测NapsinA、TTF-1、CK5/6、CK7及P63在非小细胞肺癌(NSCLC)支气管镜活检标本中的表达及意义.方法 采用免疫组织化学SP法检测47例NSCLC支气管镜活检标本中NapsinA、TTF-1、CK5/6、CK7及P63的表达,并结合NSCLC的临床特征病理进行分析.结果 NapsinA、TTF 1和CK7在27例肺腺癌中的阳性表达率分别为100％(27/27)、100％(27/27)和93％(25/27),表达水平明显高于CK5/6[19％(5/27)]和P63[0(0/27)](P＜0.05);而CK5/6和P63在18例肺鳞癌中的阳性率均为100％(18/18),表达水平明显高于NapsinA及TTF 1[0(0/18)、0(0/18)]和CK7[11％(2/18)](P＜0.05),两者差异均具有统计学意义.结论 NapsinA、TTF-1、CK7、CK5/6及P63在肺支气管镜活检标本腺癌和鳞癌鉴别诊断中具有重要意义.     

p70/p85 核糖体蛋白S6激酶1重组真核表达载体的构建及其在人乳腺癌MCF-7细胞内功能的初步鉴定

目的：构建p70 核糖体蛋白S6激酶1（p70 ribosomal protein S6 kinase 1,p70 S6K1）及p85 S6K1基因的真核表达载体pcDNA3.1(-)-flag-p70 S6K1和pcDNA3.1(-)-flag-p85 S6K1,并鉴定其在人乳腺癌MCF-7细胞内的表达及功能。 方法： 以pRK7-HA-S6K1为模板,采用PCR扩增出目的基因片段p70 S6K1、p85 S6K1,克隆入真核表达载体pcDNA3.1(-)-flag构建重组表达载体pcDNA3.1(-)-flag-p70 S6K1和pcDNA3.1(-)-flag-p85 S6K1,采用PCR、双酶切和DNA测序鉴定。将重组载体转染MCF-7细胞,24 h后采用Western blotting方法检测细胞内p70 S6K1、p85 S6K1蛋白的表达;同时向转染细胞内加入1 mmol/L H2O2处理36 h,观察p70 S6K1、p85 S6K1蛋白对H2O2诱导的细胞死亡的影响。 结果： 成功扩增得到p70 S6K1、p85 S6K1基因片段并构建重组真核表达载体pcDNA3.1(-)-flag-p70 S6K1和pcDNA3.1(-)-flag-p85 S6K1,重组载体经PCR、双酶切鉴定均出现p70 S6K1和p85 S6K1预期条带,DNA测序结果显示其全长基因阅读框完整、正确。重组载体在MCF-7细胞中高效表达flag-p70 S6K1和flag-p85 S6K1,且p85 S6K1能增强H2O2诱导的细胞死亡。 结论：成功构建重组真核表达载体pcDNA3.1(-)-flag-p70 S6K1和pcDNA3.1(-)-flag-p85 S6K1,均能在MCF-7细胞中高效表达,且p85 S6K1能够增强H2O2诱导的细胞死亡。     

放疗前中性粒细胞/淋巴细胞血小板/淋巴细胞预后营养指数及CA19-9与胰腺腺癌放疗后预后关系的分析

  目的  探讨胰腺癌患者放疗前外周血中性粒细胞与淋巴细胞的比值（neutrophil to lymphocyte ratio,NLR）、血小板与淋巴细胞的比值（platelet to lymphocyte ratio,PLR）、预后营养指数（prognostic nutritional index,PNI）及糖类抗原19-9（carbohydrate antigen 19-9,CA19-9）与总生存时间（overall survival,OS）关系。  方法  回顾性分析2008年3月~2013年3月空军总医院61例经病理确诊为胰腺腺癌的患者临床资料,并通过电子病历查询患者治疗前检验结果,通过电子病历记录或电话随访获得患者OS。采用Ka? plan-Meier方法构建生存曲线,组间差异比较用Log-rank检验,单因素及多因素的分析运用Cox比例风险模型进行。  结果  利用log-rank检验及单因素回归分析,提示NLR、PLR、CA19-9增高、PNI降低、TNM分期晚,患者生存期短,差异具有统计学意义。多因素回归分析显示,NLR（P=0.029,OR 2.344,95%CI:1.090~5.041）;PNI（P=0.026,OR 0.477,95%CI:0.248~0.917）是胰腺癌患者OS的独立影响因素。  结论  NLR、PLR、PNI等是评价胰腺癌患者预后较为简单、有效的可靠指标之一.      

K-Ras gene mutation status as a prognostic and predictive factor in patients with colorectal cancer undergoing irinotecan- or oxaliplatin-based chemotherapy

Background: CRC caused more than 600,000 estimated deaths in 2008. Dysregulated signaling through the RAS/RAF/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway due to mutations in K-Ras and B-Raf are common events in CRC. Methods: Incidence of mutations in codons 12 and 13 of K-Ras and exons 11 and 15 of B-Raf were analyzed in amplified PCR products from primary tumors of 273 patients with CRC, and their prognostic and predictive significance was assessed. The prognostic role of clinical and pathological factors was also examined. Results: K-Ras mutations were present in 89 patients (32.6%), of whom 76 (85.4%) had mutations in codon 12 and 10 (11.2%) had mutations in codon 13. B-Raf gene mutations were present in 17 patients (6.9%), of whom 6 (35.3%) had mutations in exon 15. Multivariate analysis revealed a predictive significance for K-Ras mutations with respect to time to progression in patients treated with irinotecan and oxaliplatin as first-line chemotherapy. There was no predictive significance for B-Raf gene mutation status in these patients. The following risk factors were found to affect overall survival (OS) rates: primary tumor location, lymph node involvement grade, carcinoembryonic antigen (CEA) level before treatment, and performance status according to WHO criteria. Conclusions: Based on the results of this study, K-Ras mutation status may be a suitable indicator of patient eligibility and a prognostic indicator for responsiveness to anti-EGFR therapy alone, or in combination with chemotherapy. Also, K-Ras mutation status may predict time to progression in patients treated with irinotecan and oxaliplatin.