CTHRC1 and PD­1/PD­L1 expression predicts tumor recurrence in prostate cancer.

ABSTRACT

Collagen triple helix repeat containing 1 (CTHRC1) is a gene that has been associated with tumor progression in human prostate cancer (PC). The tumor immune microenvironment has been linked with disease outcome in PC. In the present study, the correlation between CTHRC1 with PC recurrence and the tumor immunological microenvironment was investigated. Using the data supplied by the Tumor Immune Estimation Resource (TIMER), the expression of CTHRC1, programmed cell death protein 1 (PD­1), and programmed cell death 1 ligand 1 (PD­L1) were analyzed. Immunohistochemical staining of CTHRC1, PD­1 and PD­L1 was performed using a tissue microarray construction of prostate adenocarcinoma (PRAD) specimens. In PRAD, an association was reported between the CTHRC1 expression and the disease free survival (DFS) rate (P=0.022). Overexpression of CTHRC1 was correlated with increased levels of PD­1 (R=0.272, P=0.021) and PD­L1 (R=0.298, P=0.016), elevated levels of infiltrating B cells (P=9.51e­11), CD4+ cells (P=1.51e­11), macrophages (P=8.25e­5), neutrophils (P=2.17e­9) and dendritic cells (P=3.13e­13). Bioinformatics analysis revealed that CTHRC1 was correlated with the expression levels of matrix metalloproteinase­9, mucin 1 and solute carrier organic anion transporter family member 2B1 genes, which exert an influence in PRAD. The occurrence of this condition is most likely to be associated with regulation of the tumor microenvironment. Taken together, we demonstrated that the prognosis and immunity of PC are closely linked to CTHRC1 upregulation. Furthermore, these results suggest that the immune function of PC may be suppressed by CTHRC1­targeting therapy.