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. 2019 Feb 1;9(2):363-377.
eCollection 2019.

SFRP4 is a prognostic marker and correlated with Treg cell infiltration in pancreatic ductal adenocarcinoma

Min-Wei Yang  1 , Ling-Ye Tao  1 , Jian-Yu Yang  1 , Yong-Sheng Jiang  1 , Xue-Liang Fu  1 , Wei Liu  1 , Yan-Miao Huo  1 , Jiao Li  1 , Jun-Feng Zhang  1 , Rong Hua  1 , Xiao-Ran Qin  1 , Yong-Wei Sun  1 , De-Jun Liu  1
Affiliations

VSports注册入口 - SFRP4 is a prognostic marker and correlated with Treg cell infiltration in pancreatic ductal adenocarcinoma

Min-Wei Yang et al. Am J Cancer Res. .

Abstract (VSports app下载)

Secreted Frizzled-Related Protein 4 (SFRP4), a member of secreted frizzled-related protein family, has been found as a vital modulator in cell proliferation, cell self-renew and apoptosis through Wnt signaling transduction pathway VSports手机版. In the present study, we re-analyzed the expression pattern of SFRPs in Gene Expression Omnibus (GEO) datasets and evaluated the expression of SFRP4 at protein level in both KrasG12D/+; Trp53R172H/+; Pdx1-Cre; (KPC) mice and human pancreatic ductal adenocarcinoma (PDAC) tissue. We found that the expression of SFRP4 increased gradually in PanINs and PDAC lesions in KPC mice and high expression of SFRP4 was much more common in tumor lesions compared to the adjacent non-tumor tissues. Then we performed Kaplan-Meier survival and Cox regression analysis and found that high expression of SFRP4 in the serum and tumor lesions predicted poor prognosis for pancreatic cancer patients. Furthermore, we demonstrated that SFRP4 positively correlated with FOXP3+ Treg cells infiltration while the down-regulation of SFRP4 in tumor cells impaired the production of cytokines and the recruitments of T cells. This study suggested that SFRP4 can be a novel prognostic biomarker and potential therapeutic target for pancreatic cancer. .

Keywords: SFRP4; biomarkers; pancreatic ductal adenocarcinoma; prognosis; regulatory T-cell. V体育安卓版.

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Conflict of interest statement

None.

Figures

Figure 1
Figure 1
SFRP4 expression in PDAC tissue at mRNA level. A. Re-analysis the expression of SFRPs in GSE 15471 and GSE 28735. Expression of SFRPs in tumor (T) and adjacent non-tumor tissue (ANT) are shown, error bars in the column represent SE. B-D. Expression of SFRP4 was significantly increased in tumor tissues (T) compared to the adjacent non-tumor tissues (ANT) in GSE 15471, GSE 28735 and Renji cohorts. E. Representative IHC staining of SFRP4 in normal pancreas, different stage of PanINs and PDAC lesions.
Figure 2
Figure 2
SFRP4 expression in PDAC tissue microarray by IHC. A. PDAC, scored as (+++); B. PDAC, scored as (++); C. PDAC, scored as (+); D. PDAC, scored as (-); E. Adjacent non-tumor tissue, scored as (-); F. Adjacent non-tumor tissue, the islet cells scored as (+++).
Figure 3
Figure 3
SFRP4 expression is associated with overall survival in PDAC patients. A. Kaplan-Meier survival curves demonstrated that high expression of SFRP4 was significantly correlated with poor survival time of PDAC (P=0.007). p-values were statistically calculated by log-rank test. B. The serum level of SFRP4 in healthy donor and PDAC patients. C. High concentration of SFRP4 at serum level was correlated with poor prognosis for PDAC patients.
Figure 4
Figure 4
Correlation between SFRP4 expression and Treg cell infiltration in PDAC. A, B. GSEA shows the presentative GO term of biological process that positive correlates with SFRP4. C. The correlation between the expression of signature genes of T cell, CD8 cell, T helper cell, Treg cell and the expression of SFRP4. The size of the dots represents the correlation coefficient and the blue dots represent the positive correlation while the red dots represent the negative correlation. The data was analyzed from TCGA-PAAD database and demonstrated by Cytoscape.
Figure 5
Figure 5
Down-regulation of SFRP4 impairs the recruitment of T cells. A. The presentative image of FOXP3 staining by IHC. The asterisks marked the FOXP3+ Treg cells. B. The patients with high SFRP4 expression demonstrated a greater proportion of high infiltration of FOXP3+ Treg cells. C. The presentative image of SFRP4 and FOXP3 staining by IHC in the tumor tissue from KPC mice.
Figure 6
Figure 6
Down-regulation of SFRP4 decreased chemokine secretion. A. The mRNA expression of SFRP4 in cell lines. B. The down-regulation of SFRP4 by small interference RNA. C. The expression of cytokines at mRNA level influenced by SFRP4 siRNA. D. The proportion of counting beads and total migrated cell by flow cytometry. E. The gating strategy for the CD4 positive T cells. F. The precision number of total migrated cells and migrated CD4 positive cells. G. The level of β-catenin in the cell plasma and in the nuclear determined by western blot.
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