Identification of CTRP1 as a Prognostic Biomarker and Oncogene in Human Glioblastoma

Glioblastoma (GBM) is the most frequent and malignant type of primary brain tumors in adults. The valuable prognostic biomarkers and therapeutic targets for GBM remain to be elucidated. The association of adipokines with cancer has been well documented. The C1q/TNF-related protein 1 (CTRP1), a novel adipokine, belongs to the CTRP family.

In the present study, the expression and potential roles of CTRP1 in GBM were explored based on in silico evaluation, including GEPIA, the Pathology Atlas of the Human Protein Atlas, cBioPortal, TIMER, and SurvExpress. The CCK8, transwell, and wound healing assays were used to detect cell proliferation and migration.

It was found that mRNA expression levels of CTRP1 were significantly upregulated in GBM tissues compared with those in nontumor tissues according to the analysis on public dataset and immunohistochemical results of GBM tissues (P<0.05). CTRP1 was mainly localized in the cytoplasm and cell membrane of GBM cells. The genetic alterations of CTRP1 occurred at a low rate in GBM (2 of 591 sequenced cases/patients, 0.33%). The mRNA expression levels of CTRP1 were positively associated with the tumor-infiltrating macrophages and CCL2 in GBM (P<0.05, respectively). The higher mRNA expression levels of CTRP1 were significantly correlated with higher risk and shorter overall survival time in GBM (P<0.05). CTRP1 knockdown significantly inhibited the proliferation and migration in human GBM cells, suggesting the inhibition of CTRP1 on human GMB progression. Moreover, CTRP1 knockdown inhibited CCL2 expression, and CCL2 overexpression reversed the inhibition of cell proliferation and migration induced by CTRP1 knockdown, suggesting that CTRP1 promoted tumor progression by regulating CCL2 expression.

These findings suggest that CTRP1 potentially indicates poor prognosis in GBM and promotes the progression of human GBM.