Farneosid X reseptörüne ait tek nükleotid polimorfizmlerinin insanda hepatosellüler karsinom gelişimiyle ilişkisi
Küçük Resim Yok
Tarih
2023
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Giriş ve Amaç: Hepatosellüler karsinom (HCC), karaciğer en sık primer kanseri olup prognozu oldukça kötü bir hastalıktır. Ülkemizde ve dünyada görülme sıklığı artmakta ve her geçen gün daha fazla ölüme neden olmaktadır. Bu nedenle yüksek riskli kişilerde HCC gelişimini erken saptayabilmek hayati önem taşımaktadır. Bu çalışma ile daha önce hepatoprotektif rolü ortaya konulan Farnesoid X reseptörü (FXR) genine ait dört adet tek nükleotid polimorfizminin karaciğer sirozu zemininde HCC gelişimi ve HCC prognozu ile ilişkileri etkileri incelenmiştir. Gereç ve Yöntem: Araştırma, bir olgu-kontrol çalışması olarak tasarlanmış ve çalışmaya 2021 ve 2022 yıllarında Ege Üniversitesi Gastroenteroloji Kliniğine başvuran seçilmiş kriterlere uygun 101 HCC tanısı olmayan karaciğer sirozu hastası, 101 karaciğer sirozu zemininde HCC tanısı almış hastalar dahil edilmiştir. Çalışmaya dahil edilen her hastadan polimorfizm analizinde kullanılmak üzere periferik kan numunesi alınmış ve her hastanın demografik özellikleri, özgeçmişleri, aile öyküleri ve laboratuvar tetkikleri kaydedilmiştir. Polimorfizm analizleri ile saptanan genotiplerin, hastaların özellikleri ile ilişkileri incelenmiştir. Bulgular: Çalışmada yer alan 202 hastanın 140'ı (%69,3) erkek, 62'si (%30,7) kadındır. Erkek/kadın oranları olgu grubunda 84/17, siroz grubunda 56/45 (p<0,0001) bulunmuştur. Çalışmaya alınan tüm hastaların 62'si (%30,7) çalışma sürecinde hayatını kaybetmiştir. HCC hastalarının 47'si (%46,5), siroz hastalarının 15'i (%14,9) ölmüştür (p<0,0001). Olgu ve kontrol gruplarında rs56163822 GT genotiplerinin dağılımı (%5,9'a karşı %5, p=0,757) , rs35724 CC/CG/GG genotiplerinin dağılımı (%20,8/%48,5/%30,7'e karşı %15,8/%50,5/%33,7; p=0,652), rs11110385 CC, CT, TT genotiplerinin dağılımı (%51,5/ %41,6/%6,9'e karşı %43/%49/%8; p= 0,484), rs11110390 CC, CT, TT genotiplerinin dağılımı (%56,4/%43,3/%6'ya karşı %45/%48/%7; p= 0,263) benzerdir. Tüm hastalara bakıldığında rs56163822 GG genotipinde asit görülme oranı GT genotipine göre daha yüksektir (%16,7'ye karşı %67,4; p= 0,021). Tüm hastalar için rs35724 GG genotipinde CG genotipine göre daha fazla özofagus varis kanaması (ÖVK) görülmüştür (%38,5'e karşı %19; p= 0,022). Yine tüm hastalar için, rs11110390 TT genotipine sahip hastalar CC ve CT genotiplerine sahip olanlara göre daha fazla kompanse seyretmiştir (%92'ye karşı %50/%55; p=0,0231). HCC hastaları için yapılan yaşam süresi analizlerinde medyan yaşam süresi 22 ay olarak bulunmuştur. Çok değişkenli Cox regresyon analizinde asit varlığı (p=0,0005), GGT(p=0,0005), log AFP (tanı anındaki; p=0,0002), HCC'nin infiltratif özellikte olması (p=0,0168), hepatik ven tutulumu (p=0,0003) HCC hastalarında mortalite ile ilişkili bulunmuştur. Bu parametrelerden geliştirilen prognostik indeksin ölümü ön gördürmedeki sensitivitesi %84,8; spesifitesi ise %77,4 olarak saptanmıştır. Bu prognostik indekse göre kötü prognozlu görünen 52 HCC hastası için rs35724 genotipleri ayrı olarak incelenmiş ve rs35724 GG genotipi, CG ve CC genotiplerine göre daha düşük medyan yaşam süresi ile ilişkili bulunmuştur (4 aya karşı 20 ay/24 ay; p=0,041). Ayrıca HCC hastaları içinde kötü prognozla ilişkili özellikleri olanlarda (asit olanlar, AFP>20 µg/L olanlar, albümin <3,5 mg/dl olanlar, ALP>157 U/L olanlar, Child C sirozu olanlar, hepatit C enfeksiyonu dışında etyolojiye sahip olanlar) rs35724 GG genotipi, daha düşük yaşam süresi ile anlamlı olarak ilişkili bulunmuştur. Sonuç: FXR polimorfizmlerinin karaciğer sirozu hastalarında HCC gelişimi ile bir ilişkisi bulunmamaktadır. FXR rs35724 GG genotipi kötü prognostik özelliklere sahip HCC hastalarında anlamlı olarak düşük yaşam süresi ile ilişkilidir.
Introduction and Aim: Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a poor prognosis, and its incidence is on the rise globally. Early detection of HCC in high-risk individuals is crucial in reducing the mortality rate. This study aims to investigate the correlation between the development of HCC in the context of liver cirrhosis and the effects of four single nucleotide polymorphisms (SNPs) of the Farnesoid X receptor (FXR) gene, which has previously been linked to hepatoprotection, on HCC prognosis. Materials and Methods: The study was designed as a case-control study and conducted at the Ege University Gastroenterology clinic between 2021 and 2022. The case group included patients with HCC occurring in the setting of cirrhosis, while the control group included patients with liver cirrhosis but without HCC. Peripheral blood samples were collected from all patients to perform polymorphism analysis. Additionally, demographic characteristics, medical history, family history, and laboratory test results were recorded. The study examined the relationships between the genotypes and the parametric and categorical characteristics of the patients. Results: Of the 202 patients included in the study, 140 (69.3%) were male and 62 (30.7%) were female. 84 (83.2%) of the patients in the case group were male and it was significantly higher. Of all the patients included in the study, 62 (30.7%) died during the study period. The number of patients who died in the case group was 47 (46.5%) and it was higher than the control group. In case and control groups; distribution of rs56163822 GT genotypes (5.9% vs. 5%, p=0.757), distribution of rs35724 CC/CG/GG genotypes ((20,8%/48,5%/30,7% vs. 15,8%/50,5%/33,7%; p=0.652), distribution of rs11110385 CC/CT/TT genotypes (51,5%/ 41,6%/6,9% vs. 43%/49%/8%; p= 0.484) and distribution of rs11110390 CC/CT/TT genotypes (56.4%/43.3%/6% vs. 45%/48%/7%; p= 0.263) were similar. When all patients were considered, the incidence of ascites was higher in the rs56163822 GG genotype than in the GT genotype (%67,4 vs. %16,7%; p= 0.021). For all patients, the rs35724 GG genotype had more esophageal varices bleeding than the CG genotype (38.5% vs. 19%; p= 0.022). Again, for all patients, patients with the rs11110390 TT genotype were more compensated than those with the CC and CT genotypes (92% vs. 50%/55%; p=0.0231). In the analysis of life expectancy for HCC patients, the median life expectancy was 22 months. In multivariate Cox regression analysis, ascites (p=0.0005), GGT(p=0.0005), log AFP (at diagnosis; p=0.0002), infiltrative HCC (p=0.0168), hepatic vein involvement (p=0.0003) was associated with the development of death in HCC patients. The sensitivity of the prognostic index developed from these parameters in predicting death was 84.8%; its specificity was found to be 77.4%. According to this prognostic index, the rs35724 genotypes were examined separately for 52 HCC patients who seemed to have a poor prognosis, and the rs35724 GG genotype was associated with a lower median survival (4 months vs. 20 months/24 months; p=0.041) compared to the CG and CC genotypes. In addition, without evaluation with the prognostic index; when HCC patients grouped as ascites, AFP>20 µg/L, albumin <3.5 mg/dl, ALP>157 U/L, Child C cirrhosis, and those with etiology other than hepatitis C infection, rs35724 GG genotype was significantly associated with lower life expectancy in each of the groups. Conclusion: FXR polymorphisms are not associated with the development of HCC in patients with liver cirrhosis. The FXR rs35724 GG genotype is associated with significantly lower survival in HCC patients with poor prognostic features.
Introduction and Aim: Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a poor prognosis, and its incidence is on the rise globally. Early detection of HCC in high-risk individuals is crucial in reducing the mortality rate. This study aims to investigate the correlation between the development of HCC in the context of liver cirrhosis and the effects of four single nucleotide polymorphisms (SNPs) of the Farnesoid X receptor (FXR) gene, which has previously been linked to hepatoprotection, on HCC prognosis. Materials and Methods: The study was designed as a case-control study and conducted at the Ege University Gastroenterology clinic between 2021 and 2022. The case group included patients with HCC occurring in the setting of cirrhosis, while the control group included patients with liver cirrhosis but without HCC. Peripheral blood samples were collected from all patients to perform polymorphism analysis. Additionally, demographic characteristics, medical history, family history, and laboratory test results were recorded. The study examined the relationships between the genotypes and the parametric and categorical characteristics of the patients. Results: Of the 202 patients included in the study, 140 (69.3%) were male and 62 (30.7%) were female. 84 (83.2%) of the patients in the case group were male and it was significantly higher. Of all the patients included in the study, 62 (30.7%) died during the study period. The number of patients who died in the case group was 47 (46.5%) and it was higher than the control group. In case and control groups; distribution of rs56163822 GT genotypes (5.9% vs. 5%, p=0.757), distribution of rs35724 CC/CG/GG genotypes ((20,8%/48,5%/30,7% vs. 15,8%/50,5%/33,7%; p=0.652), distribution of rs11110385 CC/CT/TT genotypes (51,5%/ 41,6%/6,9% vs. 43%/49%/8%; p= 0.484) and distribution of rs11110390 CC/CT/TT genotypes (56.4%/43.3%/6% vs. 45%/48%/7%; p= 0.263) were similar. When all patients were considered, the incidence of ascites was higher in the rs56163822 GG genotype than in the GT genotype (%67,4 vs. %16,7%; p= 0.021). For all patients, the rs35724 GG genotype had more esophageal varices bleeding than the CG genotype (38.5% vs. 19%; p= 0.022). Again, for all patients, patients with the rs11110390 TT genotype were more compensated than those with the CC and CT genotypes (92% vs. 50%/55%; p=0.0231). In the analysis of life expectancy for HCC patients, the median life expectancy was 22 months. In multivariate Cox regression analysis, ascites (p=0.0005), GGT(p=0.0005), log AFP (at diagnosis; p=0.0002), infiltrative HCC (p=0.0168), hepatic vein involvement (p=0.0003) was associated with the development of death in HCC patients. The sensitivity of the prognostic index developed from these parameters in predicting death was 84.8%; its specificity was found to be 77.4%. According to this prognostic index, the rs35724 genotypes were examined separately for 52 HCC patients who seemed to have a poor prognosis, and the rs35724 GG genotype was associated with a lower median survival (4 months vs. 20 months/24 months; p=0.041) compared to the CG and CC genotypes. In addition, without evaluation with the prognostic index; when HCC patients grouped as ascites, AFP>20 µg/L, albumin <3.5 mg/dl, ALP>157 U/L, Child C cirrhosis, and those with etiology other than hepatitis C infection, rs35724 GG genotype was significantly associated with lower life expectancy in each of the groups. Conclusion: FXR polymorphisms are not associated with the development of HCC in patients with liver cirrhosis. The FXR rs35724 GG genotype is associated with significantly lower survival in HCC patients with poor prognostic features.
Açıklama
Anahtar Kelimeler
Gastroenteroloji, Gastroenterology, Genetik, Hepatosellüler karsinom, Farnesoid X reseptör, Tek nükleotid polimorfizmi, Hepatocellular carcinoma, Farnesoid X receptor, Single nucleotide polymorphism
