RESUMEN
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.
Asunto(s)
Antígeno B7-H1/genética , Biomarcadores de Tumor , Proteínas de la Matriz Extracelular/genética , Expresión Génica , Receptor de Muerte Celular Programada 1/genética , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Adulto , Anciano , Antígeno B7-H1/metabolismo , Biología Computacional/métodos , Minería de Datos , Proteínas de la Matriz Extracelular/metabolismo , Perfilación de la Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia , Pronóstico , Receptor de Muerte Celular Programada 1/metabolismo , Neoplasias de la Próstata/mortalidad , TranscriptomaRESUMEN
Spontaneous tumor hemorrhage (TH) is frequently observed in solid tumors including human hepatocellular carcinoma (HCC). TH implies fast-growing and worse tumor immunological microenvironment; however, the underlying mechanism remains largely unknown. CLEC1B is a signature gene highly associated with tumor progression. PD-L1 expression is a key biomarker predictive of immune checkpoint therapies, which showed astonishing effect on various types of tumor. We assume that, in HCC, TH may closely associate with the expression of these two molecules. In this study, 136 patients with HCC were enrolled. qRT-PCR showed that CLEC1B expression is significantly lower in HCC tumor tissue. Immunohistochemistry of HCC tissue microarrays demonstrated that PD-L1high and CLEC1Blow expressions were significantly correlated with TH and clinicopathological features indicating worse HCC progression. According to univariate/multivariate analysis, a combination of PD-L1high and CLEC1Blow expression was an independent prognostic factor indicating the poor outcome. The prognostic value of PD-L1high and CLEC1Blow was validated by Cox proportional-hazard analyses. Collectively, tumor with TH is closely associated with CLEC1Blow & PD-L1high expression, which may imply high response of PD-L1/PD-1 immune checkpoint therapies. CLEC1B may be a potential therapeutic target for PD-L1/PD-1 immunotherapy. PD-L1high and CLEC1Blow can be a valuable prognosis factor implying worse clinical outcomes.
