scholarly journals Validation of SFRP1 Promoter Hypermethylation in Plasma as a Prognostic Marker for Survival and Gemcitabine Effectiveness in Patients with Stage IV Pancreatic Adenocarcinoma

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5717
Author(s):  
Benjamin Emil Stubbe ◽  
Stine Dam Henriksen ◽  
Poul Henning Madsen ◽  
Anders Christian Larsen ◽  
Henrik Bygum Krarup ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Prognostic Marker ◽  
Cox Regression ◽  
Stage Iv ◽  
Promoter Hypermethylation ◽  
Polymerase Chain Reaction Analysis ◽  
Rank Test ◽  
Independent Prognostic Marker ◽  
Bisulfite Treatment ◽  
Kaplan Meier

No reliable predictive blood-based biomarkers are available for determining survival from pancreatic adenocarcinoma (PDAC). This combined discovery and validation study examines promoter hypermethylation (ph) of secreted frizzled-related protein 1 (SFRP1) in plasma-derived cell-free DNA as an independent prognostic marker for survival and Gemcitabine effectiveness in patients with stage IV PDAC. We conducted methylation-specific polymerase chain reaction analysis of the promoter region of the SFRP1 gene, based on bisulfite treatment. Survival was analyzed with Kaplan–Meier curves, log-rank test, and Cox regression. The discovery cohort included 40 patients, 25 receiving Gem. Gem-treated patients with phSFRP1 had a shorter median overall survival (mOS) (4.4 months) than unmethylated patients (11.6 months). Adjusted Cox-regression yielded a hazard rate (HR) of 3.48 (1.39–8.70). The validation cohort included 58 Gem-treated patients. Patients with phSFRP1 had a shorter mOS (3.2 months) than unmethylated patients (6.3 months). Adjusted Cox regression yielded an HR of 3.53 (1.85–6.74). In both cohorts, phSFRP1 was associated with poorer survival in Gem-treated patients. This may indicate that tumors with phSFRP1 are more aggressive and less sensitive to Gem treatment. This knowledge may facilitate tailored treatment of patients with stage IV PDAC. Further studies are planned to examine phSFRP1 in more intensive chemotherapy regimens.

LAPTM4B Overexpression is a Novel Independent Prognostic Marker for Metastatic Ovarian Tumors

2012 ◽  
Vol 22 (1) ◽  
pp. 54-62 ◽  
Author(s):  
Mingzhu Yin ◽  
Chun Lou ◽  
Wang Zhang ◽  
Fanling Meng ◽  
Haiyu Zhang ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Prognostic Marker ◽  
Cox Regression ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Ovarian Tumors ◽  
Rank Test ◽  
Free Survival ◽  
Independent Prognostic Marker ◽  
Worse Prognosis

ObjectiveMetastatic ovarian tumors are a series of lethal carcinomas that almost always have bad prognosis. Their prognoses, however, vary depending on the primary tumor malignancies of each. It has been reported that LAPTM4B, a novel tumor-associated gene, might indicate a worse prognosis when it was overexpressed in other carcinomas. Therefore, the authors expected to investigate whether LAPTM4B overexpression is an independent prognostic marker in metastatic ovarian tumors.MethodsImmunohistochemistry was used to assess LAPTM4B expression in metastatic ovarian tumors from 102 patients. Subsequently, univariate and multivariate survival analyses with Cox regression were performed to determine the association between LAPTM4B expression and prognosis. To identify any differences in prognosis between the 2 groups of patients with differing primary malignancies, the log-rank test was used.ResultsThe median overall and progression-free survival rates of patients with tumors of gastrointestinal tract origin were 0.97 and 0.51 years, respectively, and both were statistically significantly lower than those of patients with tumors of breast origin (P < 0.0001), which were 2.68 and 1.96 years, accordingly. Of 102 patients, 77 were classified as having a high expression of LAPTM4B, and LAPTM4B expression had a significant association with the prognosis of metastatic ovarian tumors (P < 0.01); no statistically significant interaction between LAPTM4B expression and primary malignancies was detected (P > 0.1). On the other hand, medians of overall survival and progression-free survival of patients with tumors of gastrointestinal tract origin were significantly lower than those of patients with tumors of breast origin (P < 0.0001).ConclusionsPatients with metastatic ovarian tumors of breast origin had significantly better prognosis than those with the disease from gastrointestinal tract primary malignancies. LAPTM4B overexpression might be an independent prognostic marker of metastatic ovarian tumors.

071 Natalizumab extended interval dosing (EID) is associated with a significant reduction in progressive multifocal leukoencephalopathy (PML) risk compared with standard interval dosing (SID) in the touch® prescribing program

2018 ◽  
Vol 89 (6) ◽  
pp. A29.2-A29 ◽  
Author(s):  
Lana Zhovtis Ryerson ◽  
John Foley ◽  
Ih Chang ◽  
Ilya Kister ◽  
Gary Cutter ◽  
...  
Keyword(s):  
Cox Regression ◽  
Jc Virus ◽  
Secondary Analysis ◽  
Statistical Analysis Plan ◽  
Rank Test ◽  
Primary Analysis ◽  
Standard Interval ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Dosing Intervals

IntroductionNatalizumab, approved for 300 mg intravenous every-4-weeks dosing, is associated with PML risk. Prior studies have been inconclusive regarding EID’s impact on PML risk. The US REMS program (TOUCH) offers the largest data source that can inform on PML risk in patients on EID. This analysis aimed to determine whether natalizumab EID is associated with reduced PML risk compared with SID.MethodsInvestigators developed SID and EID definitions and finalised the statistical analysis plan while blinded to PML events. Average dosing intervals (ADIs) were ≥3 to<5 weeks for SID and >5 to≤12 weeks for EID. The primary analysis assessed ADI in the last 18 months of infusion history. The secondary analysis identified any prolonged period of EID at any time in the infusion history. The tertiary analysis assessed ADI over the full infusion history. Only anti-JC virus antibody positive (JCV Ab+) patients with dosing intervals≥3 to≤12 weeks were included. PML hazard ratios (HRs) were compared using adjusted Cox regression models and Kaplan-Meier estimates.ResultsAnalyses included 13,132 SID and 1988 EID patients (primary), 15,424 SID and 3331 EID patients (secondary), and 23,168 SID and 815 EID patients (tertiary). In primary analyses, ADI (days) was 30 for SID and 37 for EID; median exposure (months) was 44 for SID and 59 for EID. Most EID patients received >2 years SID prior to EID. The PML HR (95% CI) was 0.06 (0.01–0.22; p<0.001) for primary analysis and 0.12 (0.05–0.29; p<0.001) for secondary analysis (both in favour of EID); no EID PML cases were observed in tertiary analyses (Kaplan-Meier log-rank test p=0.02).ConclusionIn JCV Ab +patients, natalizumab EID is associated with a clinically and statistically significant reduction in PML risk as compared with SID. As TOUCH does not collect effectiveness data, further studies are needed.Study supportBiogen

Survival Outcomes for Induction vs Adjuvant Chemotherapy in Squamous Cell Carcinoma of the Maxillary Sinus

2018 ◽  
Vol 160 (4) ◽  
pp. 658-663 ◽  
Author(s):  
Phoebe Kuo ◽  
Sina J. Torabi ◽  
Dennis Kraus ◽  
Benjamin L. Judson
Keyword(s):  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Maxillary Sinus ◽  
Induction Chemotherapy ◽  
Squamous Cell ◽  
Cox Regression ◽  
Rank Test ◽  
Controlled Clinical Trial ◽  
Log Rank Test ◽  
Kaplan Meier

Objective In advanced maxillary sinus cancers treated with surgery and radiotherapy, poor local control rates and the potential for organ preservation have prompted interest in the use of systemic therapy. Our objective was to present outcomes for induction compared to adjuvant chemotherapy in the maxillary sinus. Study Design Secondary database analysis. Setting National Cancer Database (NCDB). Subjects and Methods In total, 218 cases of squamous cell maxillary sinus cancer treated with surgery, radiation, and chemotherapy between 2004 and 2012 were identified from the NCDB and stratified into induction chemotherapy and adjuvant chemotherapy cohorts. Univariate Kaplan-Meier analyses were compared by log-rank test, and multivariate Cox regression was performed to evaluate overall survival when adjusting for other prognostic factors. Propensity score matching was also used for further comparison. Results Twenty-three patients received induction chemotherapy (10.6%) and 195 adjuvant chemotherapy (89.4%). The log-rank test comparing induction to adjuvant chemotherapy was not significant ( P = .076). In multivariate Cox regression when adjusting for age, sex, race, comorbidity, grade, insurance, and T/N stage, there was a significant mortality hazard ratio of 2.305 for adjuvant relative to induction chemotherapy (confidence interval, 1.076-4.937; P = .032). Conclusion Induction chemotherapy was associated with improved overall survival in comparison to adjuvant chemotherapy in a relatively small cohort of patients (in whom treatment choice cannot be characterized), suggesting that this question warrants further investigation in a controlled clinical trial before any recommendations are made.

scholarly journals Prognostic implications of alcohol dehydrogenases in hepatocellular carcinoma

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiangye Liu ◽  
Tingting Li ◽  
Delong Kong ◽  
Hongjuan You ◽  
Fanyun Kong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cox Regression ◽  
Expression Profiles ◽  
High Expression ◽  
Rank Test ◽  
Good Survival ◽  
Alcohol Dehydrogenases ◽  
Kaplan Meier ◽  
Incidence And Mortality ◽  
Prognostic Implications

Abstract Background Hepatocellular carcinoma (HCC) is a malignancy with high incidence and mortality rates worldwide. Alcohol dehydrogenases (ADHs) are huge family of dehydrogenase enzymes and associated with the prognosis of various cancers. However, comprehensive analysis of prognostic implications related to ADHs in HCC is still lacking and largely unknown. Methods The expression profiles and corresponding clinical information of HCC were obtained from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test was employed to evaluate the expression of ADHs. Cox regression and Kaplan-Meier analyses were used to investigate the association between clinicopathological characteristics and survival. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses were performed and visualized using R/BiocManager package. Results We found that the expression of ADH1A, ADH1B, ADH1C, ADH4, and ADH6 was significantly downregulated in HCC samples compared to normal liver samples. Our univariate and multivariate Cox regression analyses results showed that high expression of ADH1A, ADH1B, ADH1C, ADH4, and ADH6 was considered as an independent factor with an improved prognosis for the survival of HCC patients. Moreover, our Kaplan-Meier analysis results also revealed that high expression of AHD1A, ADH1B, ADH1C, ADH4, and ADH6 was significantly associated with good survival rate in HCC patients. In addition, GO, KEGG, and GSEA analyses unveiled several oncogenic signaling pathways were negatively associated high expression of ADHs in HCC. Conclusion In the present study, our results provide the potential prognostic biomarkers or molecular targets for the patients with HCC.

scholarly journals Lymphopenia Is Associated with Gross Target Volumes and Fractions in Hepatocellular Carcinoma Patients Treated with External Beam Radiation Therapy and Also Indicates Worse Overall Survival

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Hai-Ge Zhang ◽  
Ping Yang ◽  
Tao Jiang ◽  
Jian-Ying Zhang ◽  
Xue-Juan Jin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Cox Regression ◽  
External Beam Radiation ◽  
Rank Test ◽  
Beam Radiation ◽  
Kaplan Meier ◽  
Target Volumes ◽  
The Relationship

Purpose. To investigate whether lymphocyte nadir induced by radiation is associated with survival and explore its underlying risk factors in patients with hepatocellular carcinoma (HCC). Methods. Total lymphocyte counts were collected from 184 HCC patients treated by radiotherapy (RT) with complete follow-up. Associations between gross tumor volumes (GTVs) and radiation-associated parameters with lymphocyte nadir were evaluated by Pearson/Spearman correlation analysis and multiple linear regression. Kaplan–Meier analysis, log-rank test, as well as univariate and multivariate Cox regression were performed to assess the relationship between lymphocyte nadir and overall survival (OS). Results. GTVs and fractions were negatively related with lymphocyte nadir (p<0.001 and p=0.001, respectively). Lymphocyte nadir and Barcelona Clinic Liver Cancer (BCLC) stage were independent prognostic factors predicting OS of HCC patients (all p<0.001). Patients in the GTV ≤55.0 cc and fractions ≤16 groups were stratified by lymphocyte nadir, and the group with the higher lymphocyte counts (LCs) showed longer survival than the group with lower LCs (p<0.001 and p=0.006, respectively). Patient distribution significantly differed among the RT fraction groups according to BCLC stage (p<0.001). However, stratification of patients in the same BCLC stage by RT fractionation showed that the stereotactic body RT (SBRT) group achieved the best survival. Furthermore, there were significant differences in lymphocyte nadir among patients in the SBRT group. Conclusions. A lower lymphocyte nadir during RT was associated with worse survival among HCC patients. Smaller GTVs and fractions reduced the risk of lymphopenia.

Prognostic value of D-dimer/fibrinogen ratio in the adverse outcomes of patients hospitalized for heart failure

2020 ◽  
Vol 14 (18) ◽  
pp. 1733-1745
Author(s):  
Tian-Jun Zhao ◽  
Qian-Kun Yang ◽  
Chun-Yu Tan ◽  
Li-Dan Bi ◽  
Jie Li ◽  
...  
Keyword(s):  
Heart Failure ◽  
Regression Analysis ◽  
Cox Regression ◽  
Prognostic Indicator ◽  
Adverse Outcomes ◽  
Rank Test ◽  
Clinical Value ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
D Dimer

Aim: To evaluate the clinical value of plasma D-dimer/fibrinogen ratio (DFR) in patients hospitalized for heart failure (HF). Methods: Clinical data of 235 patients were retrospectively analyzed. Kaplan–Meier method and Cox regression analysis were used to identify significant prognosticators. Results: The Kaplan–Meier analysis showed that a higher DFR level was significantly associated with an increase in the end point outcomes, including HF readmission, thrombotic events and death (log-rank test: p < 0.001). The multivariate Cox regression analysis showed that the high tertile of DFR was significantly associated with the study end points (HR: 2.18; 95% CI: 1.31–3.62; p = 0.003), compared with the low tertile. Conclusion: DFR is a reliable prognostic indicator for patients hospitalized for HF.

Prognostic value of immunohistochemical phenotypes (IP) of 141 operable breast cancer patients (pts) included in phase III trials of adjuvant therapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21040-21040
Author(s):  
R. Trujillo ◽  
E. Gallego ◽  
A. Márquez ◽  
N. Ribelles ◽  
J. Trigo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Regression ◽  
Phase Iii ◽  
Rank Test ◽  
Prognostic Effect ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Phase Iii Trials ◽  
Her 2

21040 Background: Gene expression arrays and IP studies classified breast cancer in three distinct subtypes: basal, HER2/neu and luminal that are associated with different clinical outcomes. Methods: In 141 pts with operable breast cancer, included in phase III trials of adjuvant therapy in our center, immunohistochemical staining was performed on 3μm sections of paraffin blocks, containing tissue-arrays of tumour tissue.A basal phenotype (BP) was defined by negative estrogen receptor (ER) and progesterone receptor (PR) and positive cytokeratin (CK) 5/6 or EGFR immunoreactivity. HER2/neu phenotype as positive c-erb B2 by HercepTest™ and luminal phenotype (LP) by positive ER, PR and CK 7/8 and negative HER-2. Survival curves were calculated by the Kaplan-Meier method. The differences between survivals were estimated using the log rank test. Multivariate Cox regression analysis was used to evaluate any independent prognostic effect of the variables on disease-free survival (DFS). Results: Complete clinical follow-up information was available for 141 pts. The median follow-up period was 52 months (range 1–103 months). During this period, 13.8% pts died from breast cancer and 27.7% pts relapsed. At the time of the primary diagnosis 10.4% of the pts had lymph node negative disease and 89.6% had positive lymph nodes. 50.8% pts received taxane chemotherapy, 7.7% Trastuzumab, 62.3% radiotherapy and 61% pts received hormonotherapy. Positivity for LP was 65.2%, BP 9.9% and Her-2 phenotype 8.5%. 16.3% didn't fit for any of the three subtypes. Median DFS for BP: 24 moths, for LP and Her-2 phenotypes median DFS was not reached. 5 years DFS were; BP: 19%, LP: 63% and Her-2: 56%. Kaplan-Meier survival analyses demonstrated that the presence of a detectable BP was highly significantly associated with a worse DFS compared with the presence of a LP, log rank test (p= 0.0001). Multivariate Cox regression analyses estimated that the prognostic effect of BP in relation to DFS was independent of lymph node, stage and tumor size, HR: 0.12 95% CI (0.05–0.2). Conclusions: We found that expression of BP was associated with poor prognostic in the context of randomized phase III trials. No significant financial relationships to disclose.

The role of serum carcinoembryonic antigen in predicting objective responses to chemotherapy and overall survival in patients with non-small cell lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18084-e18084
Author(s):  
Hongbing Liu
Keyword(s):  
Protective Factor ◽  
Cox Regression ◽  
Rank Test ◽  
Small Cell Lung ◽  
Baseline Serum ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Serum Cea ◽  
Nsclc Patients

e18084 Background: Previous studies indicated the carcinoembryonic antigen (CEA) could predict the therapeutic objective response (OR) and overall survival (OS) of patients with cancers, including non-small cell lung cancer (NSCLC). However, the role it could play in evaluating therapeutic responses and OS in patients with NSCLC requires further elucidation. Herein, we investigated the potential role of CEA in predicting OR and OS in patients with NSCLC. Methods: 689 patients with NSCLC were enrolled between January 2000 and August 2011. The correlations between the CEA levels and OR or OS were examined via statistical analyses including the chi-squared test, logistical regression, paired-samples t-test, receiver operator characteristic curve, Kaplan-Meier survival analysis, log-rank test and Cox regression model. Results: The calculated cut-off for predicting an OR to chemotherapy in patients with NSCLC was a reduction of 5.28% in serum CEA. This value demonstrated a sensitivity of 61.3% and a specificity of 62.4%. Serum CEA levels significantly decreased after two cycles of chemotherapy in NSCLC patients (t = 2.196, P = 0.031). The Kaplan-Meier survival analysis indicated no significant correlation between baseline CEA and OS (log rank test =0.079). However, according to the Cox regression analysis the number of distant metastatic organs (=1 and ≥2) was the independent risk factor of the OS (P = 0.026; P =0.003), and the cycle numbers of chemotherapy was the protective factor for OS in patients with NSCLC (P=0.011).More importantly, baseline serum CEA was significantly associated with lung adenocarcinoma and adenosquamous subtypes (P = 0.014; P = 0.017, respectively). Conclusions: Our study shows that baseline serum CEA was significantly associated with lung adenocarcinoma and adenosquamous subtypes. While the baseline level of serum CEA was not a prognostic factor, the post-treatment reduction of serum CEA level can predict the OR in patients with NSCLC,. The number of chemotherapy cycles was the independent protective factor, while the numbers of distant metastatic organs was the independent risk factor for NSCLC patients’ OS.

KRAS mutations and outcomes for patients with stage IV NSCLC treated with frontline platinum/pemetrexed based chemotherapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18139-e18139 ◽  
Author(s):  
Benjamin Levy ◽  
Nagashree Seetharamu ◽  
Stacie Richardson ◽  
Daniel Jacob Becker ◽  
Walter Choi ◽  
...  
Keyword(s):  
Stage Iv ◽  
Retrospective Chart Review ◽  
Rank Test ◽  
Fisher Exact Test ◽  
Kras Mutations ◽  
Exact Test ◽  
Kaplan Meier ◽  
Mutational Status ◽  
Former Smokers ◽  
Few Data

e18139 Background: KRAS mutations are the most common driver mutation indentified in NSCLC, occurring in 20 - 30% of adenocarcinomas. While several studies suggest KRAS predicts for lack of response to TKI therapy, few data exist regarding its association with outcomes for patients treated with cytotoxic chemotherapy. This study explores the association between KRAS mutations and outcomes (RR, PFS) in a cohort of patients treated with frontline platinum/pemetrexed (PPm) based therapy. Methods: In this retrospective chart review, we evaluated RR and PFS for 16 KRAS + EGFR – pts treated with carboplatin (AUC 5-6) or Cisplatin 75mg/m2 and (Pm)pemetrexed (500 mg/m2) +/- (B)bevacizumab 15mg/kg. For comparators, we identified 19 KRAS - EGFR - patients treated with the same regimen. Maintenance therapy with Pm or Pm+B was given at the discretion of the treating physician. KRAS and EGFR mutational status were assessed by RT-PCR on tumor tissue collected at first diagnosis. RR was assessed using RECIST criteria. Kaplan-Meier estimates for PFS were evaluating using log rank test. Fisher exact test was used to assess the association between KRAS mutation status and response rate. Results: The groups were similar in age (KRAS + mean 61 vs. 60; p=0.87), gender (62% vs. 57% F; p= 0.9), ECOG 2 (0 vs. 10%,p=0.47), smoking hx (93% vs. 94% current/former smokers, p=0.7), brain mets (0% vs. 18% p=0.22), mean number induction cycles (4 in each, p=0.6), cisplatin and bevacizumab use (12% vs 10%, p > 0.1;10% vs. 40%, p=0.10). Pm maintenance was used in 31% KRAS+ (5/16) and 26% KRAS-(5/19) (p=0.79). P+B maintenance was used in 12% (2/16) and 5% (1/19) (p=0.70). RR was 56% in the KRAS + (9/16) vs. 36% KRAS- (7/19) respectively (p=0.3). There was a statistically significant improvement in PFS in the KRAS + group (10.3 mos vs. 5.7 mos, p =0.03). Conclusions: In this small retrospective review, KRAS mutations appeared to be associated with a non-significant improvement in RR and significant improvement in PFS for patients treated with frontline PPm based therapy. Future prospective studies should investigate and validate the predictive value of KRAS for this cytotoxic regimen. [Table: see text]

hSRBC promoter CpG island hypermethylation as resistant predictive biomarker of oxaliplatin based chemotherapy in metastasic colorectal cancer patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14609-e14609
Author(s):  
Catia Moutinho ◽  
Anna Martinez-Cardus ◽  
Cristina Santos ◽  
Valentín Navarro-Perez ◽  
Eva Martinez-Balibrea ◽  
...  
Keyword(s):  
Cox Regression ◽  
Cpg Island ◽  
Methylation Status ◽  
Stage Iv ◽  
Predictive Biomarker ◽  
Promoter Hypermethylation ◽  
Chemotherapeutic Agents ◽  
P Value ◽  
Potential Biomarker

e14609 Background: Resistance acquisition to chemotherapeutic agents is one of the main problems that come up during cancer treatment. hSRBC is a tumor suppressor gene whose inactivation has been associated with malignant tumor progression. In a previous work, we investigated the influence of hSRBC promoter methylation alterations in oxaliplatin (OXA) resistance acquisition by using a CRC “in vitro” model, detecting an hSRBC promoter hypermethylation in OXA–resistant derived cells when compared with the sensitive counterpart. These results were validated by functional analyses in the same model. Taking this into account, our aim in the present work is to determine the role of hSRBC methylation status as a potential biomarker of OXA resistance, in metastatic CRC patients, treated at first line with fluouropirimidines plus OXA based chemotherapy. Methods: hSRBC promoter hypermethylation was analyzed in DNA extracted from paraffin embebbed tissue of 111 metastatic CRC tumors by using Methylation Specific PCR. Methylation data was correlated to overall response (OR) and progression free survival (PFS) by using F-Fisher test and Kaplan-Meyer Survival curves respectively. A multivariate analysis was carried out by Cox regression. p-values under 0.05 were considered statistic significant. Results: Two independent cohorts of stage IV CRC tumors were included. Twenty-two out of 111 patients received radical surgery for metastasis, that became to be a positive prognostic factor (p-value = 0.04). Gene hypermethylation was detected in a 33% of cases. Although OR was not associated with hSRBC methylation, we observed a significant correlation between hypermethylation of gene and a worse PFS in patients without metastasis surgery (Log Rank; p-value = 0.04). Conclusions: Remarkably, hSRBC promoter hypermethylation is associated with worse PFS in metastatic CRC patients. We suggest hSRBC methylation status as a predictive biomarker of OXA-based treatment outcome in metastatic CRC patients. However, further studies are warranted in order to elucidate the clinical application of these findings.

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