Dataset Information

SULF2 methylation is associated with in vitro cisplatin sensitivity and clinical efficacy for gastric cancer patients treated with a modified FOLFOX regimen.

ABSTRACT:

Objective

Biomarkers capable of discriminating the patients who are likely to respond to certain chemotherapeutic agents could improve the clinical efficiency. The sulfatases(SULFs) play a critical role in the pathogenesis of a variety of human cancers. Here, we focused our investigation on the prognostic and predictive impact of SULF2 methylation in gastric cancer.

Methods

Promoter CpG island methylation of SULF2 was analyzed in 100 gastric cancer samples. The in vitro sensitivity to cisplatin, docetaxel, gemcitabine, irinotecan and pemetrexed were determined by histoculture drug response assay(HDRA). Additionally, 56 gastric cancer patients treated with a modified FOLFOX regimen(biweekly oxaliplatin plus 5-FU and folinic acid) were retrospectively analyzed to further evaluate the prognostic and predictive impact of SULF2 methylation in gastric cancer.

Results

Methylated SULF2(SULF2M) was detected in 28 patients, while the remaining 72 patients showed unmethylated SULF2(SULF2U, methylation rate: 28%). Samples with SULF2U were more sensitive to cisplatin than those with SULF2M(inhibition rate: 48.80% vs. 38.15%, P?=?0.02), while samples with SULF2M were more sensitive to irinotecan than SULF2U(inhibition rate: 53.61% vs. 40.92%, P?=?0.01). There were no association between SULF2 methylation and in vitro sensitivity to docetaxel, gemcitabine and pemetrexed. SULF2 methylation was found to have a significant association with cisplatin efficacy(SULF2M: 57.14%, SULF2U: 80.56%, P?=?0.02) and irinotecan efficacy(SULF2M: 89.29%, SULF2U: 62.50%, P?=?0.01). Among the 56 patients receiving the modified FOLFOX regimen, a significant association was observed between survival and SULF2 methylation status(SULF2M: 309 days, 95% CI?=?236 to 382 days; SULF2U: 481 days, 95% CI?=?418 to 490 days; P?=?0.02). Multivariate analysis revealed that SULF2 methylation was an independent prognostic factor of overall survival in gastric cancer patients treated with platinum-based chemotherapy.

Conclusion

SULF2 methylation is negatively associated with cisplatin sensitivity in vitro. SULF2 methylation may be a novel prognostic biomarker for gastric cancer patients treated with platinum-based chemotherapy.

SUBMITTER: Shen J

PROVIDER: S-EPMC3790846 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

SULF2 methylation is associated with in vitro cisplatin sensitivity and clinical efficacy for gastric cancer patients treated with a modified FOLFOX regimen.

Shen Jie J Wei Jia J Wang Hao H Yang Yang Y Yue Guofeng G Wang Lin L Yu Lixia L Xie Li L Sun Xia X Bian Xinyu X Zou Zhengyun Z Qian Xiaoping X Guan Wenxian W Liu Baorui B

PloS one 20131004 10

<h4>Objective</h4>Biomarkers capable of discriminating the patients who are likely to respond to certain chemotherapeutic agents could improve the clinical efficiency. The sulfatases(SULFs) play a critical role in the pathogenesis of a variety of human cancers. Here, we focused our investigation on the prognostic and predictive impact of SULF2 methylation in gastric cancer.<h4>Methods</h4>Promoter CpG island methylation of SULF2 was analyzed in 100 gastric cancer samples. The in vitro sensitivit ...[more]

PMID: 24124496

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Project description:The genetic or abnormal activation of PI3K/PTEN signaling pathway play an important role with regard to disease progression in variety of human malignancies. Experimental and epidemiologic studies indicated that the genetic polymorphisms in the PTEN, PI3K genes are associated with cancer risk, yet little evidence exists for those 2 genes and colorectal cancer (CRC) risk. To address this, we evaluated whether PTEN rs701848, PIK3CA rs2699887 variants are associated with CRC susceptibility, clinicopathological parameters and clinical outcomes in CRC patients treated with FOLFOX (Oxaliplatin, Leucovorin, 5-Fluorouracil) regimen. A case-control study was performed in 780 CRC patients and 764 healthy controls using the TaqMan assay method. A significant increased risk of CRC was observed in patients carrying PTEN rs701848 TC or CC genotype (adjusted OR=1.306, 95% CI=1.030-1.655, P=0.027; adjusted OR=1.543, 95% CI=1.148-2.075, P=0.004, respectively), TC/CC genotype (adjusted OR=1.367, 95% CI=1.090-1.714, P=0.043) in the dominant model, and C allele (adjusted OR=1.229, 95% CI=1.067-1.416, P=0.004). However, no association was detected between rs2699887 in the PIK3CA gene and CRC risk. A significant association was found between pathological grade (Dukes A and B vs. Dukes C and D) and PIK3CA rs2699887 genotypes. Furthermore, Kaplan-Meier analysis revealed that PTEN rs701848 genotypes were significantly associated with the overall survival (OS) of CRC patients treated with FOLFOX regimen (n=780). Individuals carrying PTEN rs701848 TC or TC/CC genotypes showed significantly longer median survival time (MST) than TT genotype and significant hazard ratio (TC: adjusted HR=0.523, 95% CI=0.325-0.840, P=0.007;Tc/ccadjusted HR=0.545, 95% CI=0.351-0.845, P=0.007). Therefore, rs701848 polymorphism in the PTEN gene is associated with susceptibility to CRC, and C allele of rs701848 showed significant independent better prognosis of CRC patients treated with FOLFOX regimen. These results indicate that rs701848 in the PTEN gene might be a candidate pharmacogenomic factor to assess the susceptibility and prognosis in CRC patients.

Project description:BackgroundChinese herbal injections (CHIs) have been proven beneficial to patients with gastric cancer for improving clinical efficacy and relieving adverse reactions (ADRs) of chemotherapy. A network meta-analysis (NMA) was conducted in this study to assess the comparative efficacy and safety of CHIs combined with FOLFOX regimen for treating gastric cancer.ResultsA total of 2316 records were searched, and 81 eligible RCTs involving 15 types of CHIs and 5978 patients were included in the NMA. The results showed that patients who received Shengqifuzheng+ FOLFOX, Compound kushen+ FOLFOX, Huachansu+ FOLFOX, Astragalus+ FOLFOX, Kangai+ FOLFOX, and Lentinan injection + FOLFOX could significantly improve clinical efficacy than using FOLFOX single, and their odds ratios (OR) and 95% confidence intervals (CI)s were 1.57 (1.19,2.09), 2.12 (1.62,2.78),1.72 (1.08,2.80), 3.06 (1.01,8.99), 2.01 (1.52,2.70), and 1.99 (1.20,3.38) respectively. Furthermore, the therapy of Aidi+ FOLFOX, Shenqifuzheng+ FOLFOX, Compound Kushen+ FOLFOX, Huachansu+ FOLFOX, Astragalus polysaccharides+ FOLFOX, Kangai+ FOLFOX, Ginseng polysaccharide+ FOLFOX, Lentinan+ FOLFOX, Xiaoaiping+ FOLFOX, and Shenmai injection + FOLFOX could also achieve a higher performance status compared with FOLFOX regimen alone. Similarly, patients who received CHIs combine with FOLFOX regimen were associated with a significantly decrease the incidence of leucopenia, gastrointestinal reaction and hepatic dysfunction. Cluster analysis demonstrated that Astragalus polysaccharides+ FOLFOX, and Kangai+ FOLFOX seemed optimal therapies in improving clinical efficacy and performance status; Astragalus polysaccharides+ FOLFOX was superior in reducing leucopenia and gastrointestinal reaction; Disodium Cantharidinate and Vitamin B6+ FOLFOX was associated with favorable effects in reducing gastrointestinal reaction and hepatic dysfunction. By contrary, receiving FOLFOX regimen single was proved to rank the worst for these outcomes.Materials and methodsA comprehensive literature search was performed in several electronic databases to identify randomized controlled trial (RCTs) regarding CHIs for gastric cancer until January 10, 2017. The quality assessment was accomplished according to the Cochrane risk of bias tool and the methodological section of the CONSORT statement. And a random-effects model NMA was utilized to compare different CHIs combined with FOLFOX regimen with regard to efficacy and safety. Data were analyzed using STATA 12.0 and Win-BUGS 1.4 software.ConclusionsThe results of this NMA suggested that among 15 types of CHIs, Astragalus polysaccharides injection combined with FOLFOX regimen seemed optimal for patients with gastric cancer in improving clinical efficacy and performance status, and relieving ADRs. However, our findings should be confirmed by more prospectively designed, large-sample and multi-center RCTs.

Dataset Information

SULF2 methylation is associated with in vitro cisplatin sensitivity and clinical efficacy for gastric cancer patients treated with a modified FOLFOX regimen.

Objective

Methods

Results

Conclusion

Publications

SULF2 methylation is associated with in vitro cisplatin sensitivity and clinical efficacy for gastric cancer patients treated with a modified FOLFOX regimen.

Similar Datasets

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