دورية أكاديمية
A polymorphism in the cachexia-associated gene INHBA predicts efficacy of regorafenib in patients with refractory metastatic colorectal cancer
| العنوان: | A polymorphism in the cachexia-associated gene INHBA predicts efficacy of regorafenib in patients with refractory metastatic colorectal cancer |
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| المؤلفون: | Miyamoto Y., Schirripa M., Suenaga M., Cao S., Zhang W., Okazaki S., Berger M. D., Matsusaka S., Yang D., Ning Y., Baba H., Loupakis F., Lonardi S., Pietrantonio F., Borelli B., Cremolini C., Yamaguchi T., Lenz H. -J. |
| المساهمون: | Miyamoto, Y., Schirripa, M., Suenaga, M., Cao, S., Zhang, W., Okazaki, S., Berger, M. D., Matsusaka, S., Yang, D., Ning, Y., Baba, H., Loupakis, F., Lonardi, S., Pietrantonio, F., Borelli, B., Cremolini, C., Yamaguchi, T., Lenz, H. -J. |
| سنة النشر: | 2020 |
| المجموعة: | ARPI - Archivio della Ricerca dell'Università di Pisa |
| مصطلحات موضوعية: | Aged, Allele, Antineoplastic Agent, Colorectal Neoplasm, Female, Forkhead Box Protein O3, Genotype, Human, Inhibin-beta Subunit, Male, Middle Aged, Myostatin, Neoplasm Metastasi, Phenylurea Compound, Polymorphism, Single Nucleotide, Proportional Hazards Model, Pyridine, Retrospective Studie, Sex Factor, Smad2 Protein, Survival Rate |
| الوصف: | Activin/myostatin signaling has a critical role not only in cachexia but also in tumor angiogenesis. Cachexia is a frequent complication among patients with advanced cancer and heavily pretreated patients. We aimed to evaluate the prognostic significance of cachexia-associated genetic variants in refractory metastatic colorectal cancer (mCRC) patients treated with regorafenib. Associations between twelve single nucleotide polymorphisms in 8 genes (INHBA, MSTN, ALK4, TGFBR1, ALK7, ACVR2B, SMAD2, FOXO3) and clinical outcome were evaluated in mCRC patients of three cohorts: a discovery cohort of 150 patients receiving regorafenib, a validation cohort of 80 patients receiving regorafenib and a control cohort of 128 receiving TAS-102. In the discovery cohort, patients with any G variant in FOXO3 rs12212067 had a significantly lower response rate (P = 0.031) and overall survival (OS) than those with a T/T in univariate analysis (4.5 vs. 7.6 months, hazard ratio [HR] = 1.63, 95% confidence interval [CI] = 1.09–2.46, P = 0.012). Among female patients, those with any G variant in INHBA rs2237432 had a significantly longer OS than those with an A/A in both univariate (7.6 vs. 4.3 months, HR = 0.57, 95%CI = 0.34–0.95, P = 0.021) and multivariable (HR = 0.53, 95%CI = 0.29–0.94, adjusted P = 0.031) analysis. This association was confirmed in female patients of the validation cohort, though without statistical significance (P = 0.059). Conversely, female patients with any G allele in the control group receiving TAS-102 did not show a longer OS. This was the first study evaluating the associations between polymorphisms in cachexia-associated genes and outcomes in refractory mCRC. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/32970737; info:eu-repo/semantics/altIdentifier/wos/WOS:000576265600034; volume:15; issue:9; firstpage:e0239439; journal:PLOS ONE; http://hdl.handle.net/11568/1063529Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85091620112 |
| DOI: | 10.1371/journal.pone.0239439 |
| الإتاحة: | https://doi.org/10.1371/journal.pone.0239439Test http://hdl.handle.net/11568/1063529Test |
| رقم الانضمام: | edsbas.EF82740B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1371/journal.pone.0239439 |
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