CSRP1 Promotes Colon Adenocarcinoma Growth and Serves as an Independent Risk Biomarker for Worse Prognosis

Abstract

Background. Cysteine and Glycine Rich Protein 1 (CSRP1) belongs to the cysteine-rich protein family, which contains a unique double-zinc finger motif and is important for development and cellular differentiation. Abnormal expression of CSRP1 was reported within several malignancies such as prostate cancer and acute myeloid leukemia. Here, we explored function of CSRP1 within colon adenocarcinoma (COAD) for the first time. Methods. The mRNA levels of CSRP1 in COADs were obtained from TCGA datasets. CSRP1 protein expressions in COADs were tested via immunohistochemistry staining. Patients’ prognosis was evaluated using both univariate analysis and multivariate analysis. Two human COAD originated cancer cell lines, Caco-2, and HT-29, were used for cellular experiments including shRNA knockdown, proliferation assay, and migration assay. In vivo model was established using nude mice xenografts to further validate the role of CSRP1 in COAD progression. Results. The mRNA levels of CSRP1 are elevated in COAD specimens from patients with more advanced tumor stages and higher Carcinoembryonic Antigen (CEA) levels. In addition, higher CSRP1 mRNA level indicates worse COAD prognosis. Consistently, higher CSRP1 protein expression is correlated with worse overall survival according to both univariate and multivariate analysis, indicating that CSRP1 is a new COAD prognostic factor. Furthermore, COAD cells transfected with CSRP1-shRNAs exhibit attenuated proliferation and migration capacities. Finally, growth of xenografts originated from CSRP1-knockdown cells is inhibited comparing to the control ones. Conclusions. Expression of CSRP1 is positively correlated with COAD progression, which can promote tumor growth and migration. Higher CSRP1 can is a novel independent prognostic factor of COAD.

CSRP1 expression is associated with a mesenchymal, stroma-rich tumor profile and poor prognosis in colon cancer

“…A recent study identified that a high CSRP1 expression was an independent marker of poor prognosis (HR = 1.895, 95% CI: 1.078–3.330, p = 0.026) in TCGA COAD dataset [ 11 ]. In order to evaluate the robustness of CSRP1 as a prognostic marker across multiple cohorts, independent transcriptomic datasets were analyzed.…”

“…Analysis of the prognostic relationships of CSRP1 in the TCGA COAD dataset previously showed that its expression was associated with unfavorable prognosis [ 11 ]. However, this result has not yet been evaluated in independent cohorts.…”

“…Alternatively, the expression of CSRP1 in the tumor microenvironment of these tissues may be a critical factor underlying its relationships with disease progression. A recent study showed that the knockdown of CSRP1 in colon cancer cell lines caused a reduction in cell proliferation and migration [ 11 ]. Several studies have revealed the roles of CSRP1 also in cellular contractility and movement.…”

“…CSRP1 expression was downregulated in 15 of 19 colorectal tumors; thus, it was suggested as a potential tumor suppressor in colorectal cancer (CRC) [ 10 ]. A recent study showed that a high expression of CSRP1 was associated with poor prognosis in The Cancer Genome Atlas (TCGA) colon adenocarcinoma (COAD) cohort [ 11 ]. However, evaluation of this gene as a prognostic marker has not yet been performed in independent cohorts.…”

Data mining in acute myeloid leukemia: identification of disease biomarkers, prognostic factors, novel targets, and potential drugs

“…From a functional point of view, IL2RA acts on proliferation, differentiation, apoptosis, stem cell-related properties, and promotes leukemogenesis ( 17 ). On the other hand, the role of CSRP1 is still little known in AML, but its role as a potential oncogene was recently described in solid tumors ( 18 ). Given this background, the study conducted by Sun et al ( 5 ) proposes a new biomarker and consolidates some prognostic markers in AML, promoting progress in the field of study.…”