A study reported by Yasuhito Tanaka of the Nagoya City University Medical Department in Japan showed that the single nucleotide polymorphism (SNP) in the TLL1 gene is related to the occurrence and development of hepatocellular carcinoma after radical cure of hepatitis C virus infection. (Gastroenterology. 2017, 152: 1383-1394.) The researchers established different models by combining TLL1 gene mutation with other significant risk factors to predict the risk of liver cancer in patients with different degrees of liver fibrosis. TLL1 gene variants can be used to predict the risk of kanser sa atay in patients who have achieved a sustained virological response (SVR) in clinical practice. The study included Japanese patients who still suffered from liver cancer after interferon eradication of hepatitis C virus, and used genome-wide association analysis to identify which genes were mutated. The results showed that the TNP1 gene SNP rs17047200 on chromosome 4 is closely related to the occurrence of liver cancer after eradication of hepatitis C virus. There is no obvious linkage disequilibrium between other SNPs and rs17047200, and no more promising SNPs have been found in the exons and promoter regions of TLL1. Tanaka commented: “The mutant genes of liver cancer caused by hepatitis C virus include MICA and DEPDC5, which is very different from our test results.” In a multivariate analysis, the AT / TT base pairing of rs17047200 may lead to a 78% increased risk of liver cancer (P = 0.008). In the group of patients with mild fibrosis, older age is an independent risk factor for liver cancer; in the group of severe fibrosis, postoperative alpha-fetoprotein level and low albumin level are also risk factors. In two groups of liver fibrosis rat models, the mRNA level of TLL1 has increased, but only one group of models of TLL1 mRNA level is consistent with the progress of liver fibrosis. The level of TLL1 mRNA in patients with chronic hepatitis C also increases as liver fibrosis worsens.
Itinuro ni Tananka: "Ang mga data na ito sa simula ay nagpapakita ng kaugnayan sa pagitan ng TLL1 / Tll1 expression at hepatic stellate cell activation o hepatic fibrosis progression sa mga hayop o in vitro at sa mga tao (ang modelo ay non-alcoholic steatohepatitis-related liver cancer). Maaari nitong linawin ang isang bagong mekanismo ng fibrosis ng atay o kanser. Pagkatapos makatanggap ng radikal na paggamot ang pasyente para sa hepatitis C virus at makakuha ng SVR, maaaring gamitin ang mga eksperimento na nauugnay sa TLL1 SNP upang matukoy ang mga taong nasa panganib ng kanser sa atay. Kung ihahambing ang TLL1 SNP sa Ang kumbinasyon ng edad, antas ng fibrosis, mataas na antas ng alpha-fetoprotein at iba pang makabuluhang kadahilanan ng panganib ay maaaring makatulong sa klinikal na mahulaan ang panganib ng kanser sa atay pagkatapos ng SVR. Walang interferon oral treatment plan na sinamahan ng direct-acting antiviral drug therapy , Ay nagiging standard na anti-hepatitis C virus therapy sa mga binuo na bansa. Gayunpaman, kailangan pa rin ng karagdagang pananaliksik upang masuri kung ang mga mutasyon ng TLL1 ay nauugnay sa paglitaw ng kanser sa atay pagkatapos ng paggamot na may interferon-free SVR.
