Expression and clinicopathological significance of lactate dehydrogenase D in clear cell renal cell carcinoma
Objective To investigate the relationship between the expression of lactate dehydrogenase D(LDHD)and its clinicopathological features and prognosis in clear cell renal cell carcinoma(ccRCC),and to analyze the correlation be-tween the expression of LDHD and immune cell infiltration,immune checkpoints(ICPs).Methods We collected the clinical data and tissue specimens of 71 ccRCC patients diagnosed in the Affiliated Hospital of Binzhou Medical College from 2011-01-01-2018-12-31 and detected the expression of LDHD in normal kidney adjacent to tumor and ccRCC tumor tissue by immunohistochemistry.The expression of LDHD in normal kidney adjacent to tumor and ccRCC tumor tissue and its clinicopathological significance were analyzed.Tumor Immune Estimation Resource(TIMER)and Gene Expres-sion Profiling Interactive Analysis(GEPIA)databases were used to investigate the correlation of LDHD with immune cell infiltration and ICPs.Results LDHD protein was not expressed in glomeruli,but there was a decreasing trend in the proportion of LDHD strongly expressed in proximal convoluted tubules,myeloid loops(proximal straight tubules,thin segments,distal straight tubules),distal convoluted tubules and collecting tuducts.Compared with paracancer normal re-nal tissue,the expression level of LDHD protein in ccRCC was down-regulated(P＜0.001).Cox risk regression analysis indicated that LDHD(HR=0.310,95％CI:0.102-0.939,P=0.038),maximum tumor diameter(HR=1.349,95％CI:1.067-1.705,P=0.012),International Society of Urological Pathology grade(HR=2.473,95％CI:1.005-6.086,P=0.049),and T stage(HR=0.517,95％CI:0.268-0.995,P=0.048)were independent prognostic factors for ccRCC patients.The analysis of TIMER database showed that the logarithm of transcripts per kilobase million(TPM)of LDHD was significantly positively correlated with tumor purity(rs=0.242,P＜0.001),and negatively correlated with B cells(r,=-0.120,P=0.010),CD4+T cells(rs=-0.143,P=0.002),CD8+T cells(r,=-0.131,P=0.006),macropha-ges(rs=-0.101,P=0.033),neutrophils(rs=-0.155,P＜0.001),and dendritic cells(rs=-0.158,P＜0.001).The results of TIMER and GEPIA database showed that the logarithm of TPM of LDHD and that of PD-1(rs=-0.220,P＜0.001;r=-0.180,P＜0.001)and the logarithm of TPM of CTLA-4(rs=-0.253,P＜0.001;r=-0.260,P＜0.001)showed a negative correlation.Conclusion The expression of LDHD is low in ccRCC and negatively correlated with PD-1 and CTLA-4,suggesting that LDHD may mediate the immune escape of ccRCC,and LDHD may be the target of ccRCC immunotherapy.
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