Expression Of HnRNP L In Hepatocellular Carcinoma And Its Correlation With Macrophage Polarization

Objective Heterogeneous nuclear ribonucleoprotein L(HnRNP L)has been considered to be closely related to varieties of malignant tumors.Recently,studies have shown that high titers of hnRNP L autoantibodies are associated with increased tumor size and decreased survival in hepatocellular carcinoma(HCC)patients.However,the expression and role of hnRNP L in HCC tissues are not clear.The purpose of this study was to explore the expression of hnRNP L in HCC tissues and analyze its relationship with clinicopathological features of HCC patients and macrophage polarization.Methods The expression of hnRNP L and macrophage polarization related marker(CD68,CD206,and CD11c)in HCC tissues and para-cancerous tissues from 90 samples of HCC patients was detected by immunohistochemistry.The expression levels of hnRNP-L in 20 paired HCC and para-cancerous tissues were assessed by qRT-PCR and Western blot assays.Besides,the expression of long intergenic non-coding RNA-EPS(lincRNA-EPS)was also assessed.Finally,statistical analysis was performed on the above data.Results Results of immunohistochemistry showed that positive expression of hnRNP L was obtained in 70(77.7%)HCC tissues and 48(53.3%)para-cancerous tissues,and the difference between them was statistically significant(P=0.001).Western blot analysis indicated that the protein expression level of hnRNP L was significantly higher in HCC tissues than that of para-cancerous tissues(1.09±0.22 vs 0.48±0.11,P<0.001).Moreover,the relative mRNA expression levels of hnRNP L in HCC tissuesand the corresponding para-cancerous tissues were 1.19 ± 0.51 and 0.61 ± 0.31,(P<0.001).Clinicopathological features analysis showed that high-level expression of hnRNP L in HCC tissues was significantly associated with age,vascular invasion,Edmondson grade and Barcelona Clinic Liver Cancer stage(P=0.018,P=0.039,P=0.001,P=0.018).Immunohistochemical analysis of serial sections showed that the expression intensity of hnRNP L was positively consistent with the expression of CD68(TAMs marker)and CD206(M2 type macrophage marker)(? =0.448,? =0.455,P<0.001,P<0.001),but negatively consistent with the expression of CD11c(M1 type macrophage marker)(?=-0.394,P<0.001).Also,the result showed that lincRNA EPS was significantly higher in HCC tissues than that of para-cancerous tissues(1.66±0.64 vs 0.87±0.33,P<0.001).Conclusion The expression of hnRNP L in HCC tissues was significantly higher than that in adjacent tissues and correlated with the malignant characteristics of HCC.At the same time,the expression of hnRNP L was correlated to the polarization of macrophages,suggesting that hnRNP L may regulate the development of HCC by participating in the polarization of macrophages,which provide some new references for further understanding the molecular mechanism of HCC.