The T393C polymorphism of GNAS1 as a predictor for chemotherapy sensitivity and survival in advanced non-small-cell lung cancer patients treated with gemcitabine plus platinum

Xie, Fajun; Zhao, Peng; Kou, Junyan; Hong, Wei; Fu, Li; Hu, Lin; Hong, Dan; Su, Dan; Gao, Yun; Zhang, Yiping

doi:10.1007/s00280-012-1849-3

Cited by 8 publications

(3 citation statements)

References 18 publications

(22 reference statements)

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“…However, predictive markers for response to this regimen are still limited. Our recent study showed that T393C polymorphism of Gs protein α subunit (GNAS1) gene was a predictor for clinical outcomes in advanced NSCLC patients treated with gemcitabine/platinum (Xie et al, 2012). In the current study, we tried a combination of gene polymorphisms potentially related with the effect of this regimen.…”

Section: Discussionmentioning

confidence: 99%

Methylenetetrahydrofolate reductase C677T polymorphism predicts response and time to progression to gemcitabine-based chemotherapy for advanced non-small cell lung cancer in a Chinese Han population

Hong

Wang

Zhang

et al. 2013

J. Zhejiang Univ. Sci. B

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Abstract:Objective: The aim of this study was to evaluate the association between the methylenetetrahydrofolate reductase (MTHFR) C677T excision repair cross-complementation group 1 (ERCC1) genetic polymorphisms and the clinical efficacy of gemcitabine-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Methods: A total of 135 chemonaive patients with unresectable advanced NSCLC were treated with gemcitabine/platinum regimens. The polymorphisms of MTHFR C677T, ERCC1 C8092A, and ERCC1 C118T were genotyped using the TaqMan methods. Results: The overall response rate was 28.9%. Patients with MTHFR CC genotype had a higher rate of objective response than patients with variant genotype (TT or CT) (41.2% versus 19.1%, P=0.01). Median time to progression (TTP) of patients with MTHFR CC genotype was longer than that of patients with variant genotype (7.6 months versus 5.0 months, P=0.003). No significant associations were obtained between ERCC1 C118T and C8092A polymorphisms and both response and survival. Conclusions: Our data suggest the value of MTHFR C677T polymorphism as a possible predictive marker of response and TTP in advanced NSCLC patients treated with gemcitabine/platinum.

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Section: Discussionmentioning

confidence: 99%

Methylenetetrahydrofolate reductase C677T polymorphism predicts response and time to progression to gemcitabine-based chemotherapy for advanced non-small cell lung cancer in a Chinese Han population

Hong

Wang

Zhang

et al. 2013

J. Zhejiang Univ. Sci. B

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“…Until now, there has been no research demonstrating that activating or inactivating mutations or epigenetic changes of GNAS have prognostic and not diagnostic value. The T393C pleomorphism of the GNAS locus has been identified to have prognostic value in various malignant tumors, including clear cell renal cell carcinoma (29), bladder cancer (30), colorectal cancer (31), epithelial ovarian cancer (32), melanoma (33), glioblastoma (34) and non-small cell lung cancer (35).…”

Section: A B C Dmentioning

confidence: 99%

Clinicopathological implications of GNAS in Ewing sarcoma

et al. 2016

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Abstract. The objective of the present study was to determine whether guanine nucleotide-binding protein α stimulating (GNAS) gene expression correlates with pathognomonic signs by analyzing the mutations, methylation status and G-protein α subunit (G sα ) expression of GNAS in Ewing sarcoma (ES). Formalin-fixed paraffin-embedded tissue samples from 77 patients with primary ES were obtained in South Korea, Argentina and Brazil, and were studied via methylation chip assay and direct sequencing of the GNAS gene and immunohistochemical analysis of G sα . The mutation and methylation statuses of the GNAS gene were examined. Immunohistochemical results were measured with respect to proportion and staining intensity. The results revealed that GNAS genes in ES tumor samples were less methylated compared with normal controls. No mutations were detected at exons 8 or 9 of the GNAS locus complex on chromosome 20q13.3, indicating that the pathogenesis of ES was not associated with GNAS mutation. G sα expression correlated well with the methylation status of the GNAS gene. Notably, high G sα expression was detected more frequently in samples from living patients than from decedents, although this was not statistically significant (P=0.055). In conclusion, GNAS mutation is not associated with the pathogenesis of ES tumors. This finding may be used to differentiate ES tumors from metastatic bone lesions with morphological similarity to ES tumors. Analysis of the methylation status of the GNAS gene and immunohistochemical G sα expression suggests that hypermethylated GNAS (low G sα expression) in ES may be associated with unfavorable progression with a non-significant trend.

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“…Because of its high fatality (the overall ratio of mortality to incidence is 0.87), large numbers of studies focus on the prevention and treatment of lung cancer. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases (Xie et al, 2012). In NSCLC, almost half of the patients have advanced and metastatic disease and have missed the opportunity to have surgery.…”

Section: Introductionmentioning

confidence: 99%

Correlation of MSH3 polymorphisms with response and survival in advanced non-small cell lung cancer patients treated with first-line platinum-based chemotherapy

Yao

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Mismatch repair (MMR) genes, as well as the nucleotide excision repair genes, play an important role in removing cisplatin-DNA adducts, and the mutation of MMR genes in tumors can lead to a decreased response to platinum-based therapies. We examined MutS homolog 3 (MSH3), a mismatch repair gene, and whether polymorphisms of MSH3 were associated with response and survival in advanced non-small cell lung cancer (NCSLC) patients who were treated with platinum-based chemotherapy. The peripheral blood of 180 advanced NCSLC patients who were treated with first-line platinum-based chemotherapy was collected to determine the patients' genotypes of MSH3. The three genotypes of the MSH3 polymorphisms rs26279, rs1650697 and rs1105524 were investigated. A statistically significant association was observed between the polymorphism (2015) rs26279 (Ala1054Thr) and sensitivity to platinum-based chemotherapy (P = 0.014). A significant correlation was found between rs1105524 and progression-free survival (PFS), with the G/A and A/A genotypes (median survival time: 14.27 months; 95%CI = 9.80-18.75) suffering shorter survival than patients with the G/G genotype (median survival time: 26.37 months; 95%CI = 15.03-37.71) (P = 0.04). Our results showed that single nucleotide polymorphisms in MSH3 had an impact on the chemotherapy response and prognosis of advanced NCSLC patients who were treated with platinum-based chemotherapy.

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The T393C polymorphism of GNAS1 as a predictor for chemotherapy sensitivity and survival in advanced non-small-cell lung cancer patients treated with gemcitabine plus platinum

Abstract: This study suggests that the TT genotype of the GNAS1 T393C polymorphism could be an independent prognostic marker to predict chemotherapy sensitivity, favorable OS and PFS in advanced NSCLC patients with GP treatment.

Cited by 8 publications

References 18 publications

Methylenetetrahydrofolate reductase C677T polymorphism predicts response and time to progression to gemcitabine-based chemotherapy for advanced non-small cell lung cancer in a Chinese Han population

Methylenetetrahydrofolate reductase C677T polymorphism predicts response and time to progression to gemcitabine-based chemotherapy for advanced non-small cell lung cancer in a Chinese Han population

Clinicopathological implications of GNAS in Ewing sarcoma

Correlation of MSH3 polymorphisms with response and survival in advanced non-small cell lung cancer patients treated with first-line platinum-based chemotherapy

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