AKT1 and SELP polymorphisms predict the risk of developing cachexia in pancreatic cancer patients.
Pancreatic ductal adenocarcinoma (PDAC) patients have the highest risk of developing cachexia, which is a direct cause of reduced quality of life and shorter survival. Novel biomarkers to identify patients at risk of cachexia are needed and might have a substantial impact on clinical management. Her...
Guardado en:
| Autores principales: | , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2014
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/bebe4ffa80444420a10125426b584cca |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:bebe4ffa80444420a10125426b584cca |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:bebe4ffa80444420a10125426b584cca2021-11-25T05:59:57ZAKT1 and SELP polymorphisms predict the risk of developing cachexia in pancreatic cancer patients.1932-620310.1371/journal.pone.0108057https://doaj.org/article/bebe4ffa80444420a10125426b584cca2014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0108057https://doaj.org/toc/1932-6203Pancreatic ductal adenocarcinoma (PDAC) patients have the highest risk of developing cachexia, which is a direct cause of reduced quality of life and shorter survival. Novel biomarkers to identify patients at risk of cachexia are needed and might have a substantial impact on clinical management. Here we investigated the prognostic value and association of SELP-rs6136, IL6-rs1800796 and AKT1-rs1130233 polymorphisms with cachexia in PDAC. Genotyping was performed in DNA from blood samples of a test and validation cohorts of 151 and 152 chemo-naive locally-advanced/metastatic PDAC patients, respectively. The association of SELP-rs6136, IL6-rs1800796 and AKT1-rs1130233 polymorphisms with cachexia as well as the correlation between cachexia and the candidate polymorphisms and overall survival were analyzed. Akt expression and phosphorylation in muscle biopsies were evaluated by specific ELISA assays. SELP-rs6136-AA and AKT1-rs1130233-AA/GA genotypes were associated with increased risk of developing cachexia in both cohorts (SELP: p = 0.011 and p = 0.045; AKT1: p = 0.004 and p = 0.019 for the first and second cohorts, respectively), while patients carrying AKT1-rs1130233-GG survived significantly longer (p = 0.002 and p = 0.004 for the first and second cohorts, respectively). In the multivariate analysis AKT1-rs1130233-AA/GA genotypes were significant predictors for shorter survival, with an increased risk of death of 1.7 (p = 0.002) and 1.6 (p = 0.004), in the first and second cohorts, respectively. This might be explained by the reduced phosphorylation of Akt1 in muscle biopsies from patients harboring AKT1-rs1130233-AA/GA (p = 0.003), favoring apoptosis induction. In conclusion, SELP and AKT1 polymorphisms may play a role in the risk of cachexia and death in PDAC patients, and should be further evaluated in larger prospective studies.Abolfazl AvanAmir AvanTessa Y S Le LargeAndrea MambriniNiccola FunelMina MaftouhMajid Ghayour-MobarhanMaurizio CantoreUgo BoggiGodefridus J PetersPaola PacettiElisa GiovannettiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e108057 (2014) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Abolfazl Avan Amir Avan Tessa Y S Le Large Andrea Mambrini Niccola Funel Mina Maftouh Majid Ghayour-Mobarhan Maurizio Cantore Ugo Boggi Godefridus J Peters Paola Pacetti Elisa Giovannetti AKT1 and SELP polymorphisms predict the risk of developing cachexia in pancreatic cancer patients. |
| description |
Pancreatic ductal adenocarcinoma (PDAC) patients have the highest risk of developing cachexia, which is a direct cause of reduced quality of life and shorter survival. Novel biomarkers to identify patients at risk of cachexia are needed and might have a substantial impact on clinical management. Here we investigated the prognostic value and association of SELP-rs6136, IL6-rs1800796 and AKT1-rs1130233 polymorphisms with cachexia in PDAC. Genotyping was performed in DNA from blood samples of a test and validation cohorts of 151 and 152 chemo-naive locally-advanced/metastatic PDAC patients, respectively. The association of SELP-rs6136, IL6-rs1800796 and AKT1-rs1130233 polymorphisms with cachexia as well as the correlation between cachexia and the candidate polymorphisms and overall survival were analyzed. Akt expression and phosphorylation in muscle biopsies were evaluated by specific ELISA assays. SELP-rs6136-AA and AKT1-rs1130233-AA/GA genotypes were associated with increased risk of developing cachexia in both cohorts (SELP: p = 0.011 and p = 0.045; AKT1: p = 0.004 and p = 0.019 for the first and second cohorts, respectively), while patients carrying AKT1-rs1130233-GG survived significantly longer (p = 0.002 and p = 0.004 for the first and second cohorts, respectively). In the multivariate analysis AKT1-rs1130233-AA/GA genotypes were significant predictors for shorter survival, with an increased risk of death of 1.7 (p = 0.002) and 1.6 (p = 0.004), in the first and second cohorts, respectively. This might be explained by the reduced phosphorylation of Akt1 in muscle biopsies from patients harboring AKT1-rs1130233-AA/GA (p = 0.003), favoring apoptosis induction. In conclusion, SELP and AKT1 polymorphisms may play a role in the risk of cachexia and death in PDAC patients, and should be further evaluated in larger prospective studies. |
| format |
article |
| author |
Abolfazl Avan Amir Avan Tessa Y S Le Large Andrea Mambrini Niccola Funel Mina Maftouh Majid Ghayour-Mobarhan Maurizio Cantore Ugo Boggi Godefridus J Peters Paola Pacetti Elisa Giovannetti |
| author_facet |
Abolfazl Avan Amir Avan Tessa Y S Le Large Andrea Mambrini Niccola Funel Mina Maftouh Majid Ghayour-Mobarhan Maurizio Cantore Ugo Boggi Godefridus J Peters Paola Pacetti Elisa Giovannetti |
| author_sort |
Abolfazl Avan |
| title |
AKT1 and SELP polymorphisms predict the risk of developing cachexia in pancreatic cancer patients. |
| title_short |
AKT1 and SELP polymorphisms predict the risk of developing cachexia in pancreatic cancer patients. |
| title_full |
AKT1 and SELP polymorphisms predict the risk of developing cachexia in pancreatic cancer patients. |
| title_fullStr |
AKT1 and SELP polymorphisms predict the risk of developing cachexia in pancreatic cancer patients. |
| title_full_unstemmed |
AKT1 and SELP polymorphisms predict the risk of developing cachexia in pancreatic cancer patients. |
| title_sort |
akt1 and selp polymorphisms predict the risk of developing cachexia in pancreatic cancer patients. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/bebe4ffa80444420a10125426b584cca |
| work_keys_str_mv |
AT abolfazlavan akt1andselppolymorphismspredicttheriskofdevelopingcachexiainpancreaticcancerpatients AT amiravan akt1andselppolymorphismspredicttheriskofdevelopingcachexiainpancreaticcancerpatients AT tessayslelarge akt1andselppolymorphismspredicttheriskofdevelopingcachexiainpancreaticcancerpatients AT andreamambrini akt1andselppolymorphismspredicttheriskofdevelopingcachexiainpancreaticcancerpatients AT niccolafunel akt1andselppolymorphismspredicttheriskofdevelopingcachexiainpancreaticcancerpatients AT minamaftouh akt1andselppolymorphismspredicttheriskofdevelopingcachexiainpancreaticcancerpatients AT majidghayourmobarhan akt1andselppolymorphismspredicttheriskofdevelopingcachexiainpancreaticcancerpatients AT mauriziocantore akt1andselppolymorphismspredicttheriskofdevelopingcachexiainpancreaticcancerpatients AT ugoboggi akt1andselppolymorphismspredicttheriskofdevelopingcachexiainpancreaticcancerpatients AT godefridusjpeters akt1andselppolymorphismspredicttheriskofdevelopingcachexiainpancreaticcancerpatients AT paolapacetti akt1andselppolymorphismspredicttheriskofdevelopingcachexiainpancreaticcancerpatients AT elisagiovannetti akt1andselppolymorphismspredicttheriskofdevelopingcachexiainpancreaticcancerpatients |
| _version_ |
1718414304820068352 |