The correlation between the expression of KLF6 and NAP1 L1 and the pathological characteristics of liver cancer patients and their impact on prognosis
Objective:To investigate the expression of Kruppel like factor 6 (KLF6 )protein and nucleosome assembly protein 1-like-1 (nap1 l)in hepatocellular carcinoma (HCC)and their relationship with clinical prognosis of HCC.Methods:Immunohistochemistry was used to detect KLF6 and NAP1 L1 expression in 202 hepatocellular carcinoma and paracancer tissues and 78 donor livers.Results:The positive expression rate of KLF6 was 41.09%(83 cases),and the positive expression rate of NAP1L1 was 96.53%(195 cases).In 202 cases,the positive expression rate of KLF6 was 81.19%(164 cases),and NAP1L1 was not expressed at all.In normal liver tissues,KLF6 positive expression rate was 100%(78 cases),NAP1L1 was not expressed at all.The positive rate of KLF6 expression was higher in AFP<400 μg/L group.The positive rate of KLF6 in HBV infection group was higher than that in non-HBV infection group (P<0.05).The positive rate of KLF6 was higher in the highly differentiated group (P<0.05 ).In the TMN stage group,the positive rate of KLF6 in stage Ⅰ was high(P<0.05).The positive rate of NAP1L1 was higher in AFP≥400 μg/L group.The positive rate of NAP1L1 was higher in cirrhosis group. The positive rate was higher in the direct larger tumor group (P<0.05 ).The positive rate of HBV infection was higher (P<0.05 ).The positive rate in TNMstage Ⅲ was higher (P<0.05).Spearman correlation analysis showed that KLF6 was significantly negatively correlated with AFP,tumor diameter,HBV infection,differentiation degree and TNMstage (P<0.05).NAP1L1 was positively correlated with AFP,tumor diameter,liver cirrhosis,HBV infection and TNM stage (P<0.05 ).The proportion of recurrence in KLF6 negative patients was higher (P<0.05 ).NAP1 L1 positive patients accounted for a high proportion of positive.Cox multivariate analysis of tumor recurrence showed that AFP≥400 (μg/L),tumor diameter≥5 cm,liver cirrhosis,HBV infection,differentiation degree (low differentiation),TNM stage (Ⅲ-Ⅲ stage),NAP1L1 expression (positive)were the risk factors for tumor recurrence (P<0.05).KLF6 expression (positive)was a protective factor for tumor recurrence (P<0.05).The survival rate of 202 patients with liver cancer was 87.62%in six months,69.31%in one year and 59.41%in 1.5 years.Survival analysis showed that patients with negative KLF6 and NAP1L1 had a longer survival time than those with positive KLF6 and NAP1L1.The median survival time of KLF6-positive patients with liver cancer was 41.05 months and that of negative patients was 54.15 months.The median survival time of patients with NAP1L1 positive liver cancer was 44.97 months,and that of patients with NAP1L1 negative liver cancer was 57.20 months,the difference was statistically significant.ROC curve results showed that the area under the curve (AUC)of NAP1L1 was 0.754,the optimal Cut-off value was 0.619,the sensitivity was 63.8%,the specificity was 85.1%,and the cut-off was 8.052.The AUC of KLF6 was 0.835,the sensitivity was 64.2%,and the specificity was 93.1%.The AUC of the combined diagnosis of liver cancer was 0.890,the optimal Cut-off value was 0.721,the sensitivity was 59.3%,the specificity was 98.6%,and the cut-off was 7.418.Conclusion:Transcription factors KLF6 and NAP1L1 may play important roles in the development of liver cancer,and their abnormal expression is often associated with low AFP levels,HBV infection,low differentiation,and is associated with poor prognosis in patients.
liver cancerKruppel like factor 6protein and nucleosome assembly protein 1-like-1