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Increased RIPK4 expression is associated with progression and poor prognosis in cervical squamous cell carcinoma patients.

Liu DQ, Li FF, Zhang JB, Zhou TJ, Xue WQ, Zheng XH, Chen YB, Liao XY, Zhang L, Zhang SD, Hu YZ, Jia WH - Sci Rep (2015)

Bottom Line: Further, RIPK4 overexpression was associated with overall (HR = 2.085, P = 0.038) and disease-free survival (HR = 1.742, P = 0.037).Knockdown of RIPK4 reduced cell migration and invasion via inhibition of Vimentin, MMP2 and Fibronectin expression in cervical cancer cells.RIPK4 might act as a potential diagnostic and independent prognostic biomarker for CSCC patients.

View Article: PubMed Central - PubMed

Affiliation: Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.

ABSTRACT
Aberrant expression of receptor interacting protein kinase 4 (RIPK4), a crucial regulatory protein of Wnt/β-catenin signaling, has recently been reported to be involved in several cancers. Here, we report the potential clinical implication and biological functions of RIPK4 in cervical squamous cell carcinoma (CSCC). One hundred and ninety-eight CSCC cases, 109 low-grade squamous intraepithelial lesions (LSILs), 141 high-grade squamous intraepithelial lesions (HSILs) and 63 chronic cervicitis were collected. The expression of RIPK4 was detected by immunohistochemistry (IHC), and its clinical value and oncogenic functions were further assessed. RIPK4 expression increased significantly with disease progression from 3.2% in chronic cervicitis, 19.3% in LSILs and 85.1% in HSILs to 94.4% in CSCCs (P < 0.001). Moreover, RIPK4 may serve as a useful biomarker to distinguish HSIL from chronic cervicitis/LSIL, which are two different clinical types for therapeutic procedures, with a high sensitivity and specificity (85.1% and 86.6%, respectively) and the performance improved when combined with p16(INK4a). Further, RIPK4 overexpression was associated with overall (HR = 2.085, P = 0.038) and disease-free survival (HR = 1.742, P = 0.037). Knockdown of RIPK4 reduced cell migration and invasion via inhibition of Vimentin, MMP2 and Fibronectin expression in cervical cancer cells. RIPK4 might act as a potential diagnostic and independent prognostic biomarker for CSCC patients.

No MeSH data available.


Related in: MedlinePlus

qRT-PCR, western blot and immunohistochemistry analyses of RIPK4.(a) qRT-PCR analysis of RIPK4 mRNA expression in 101 fresh CSCC tissues (T) and 30 paracancerous tissues (N). Expression levels were normalized to those of EFF1A1. (b) RIPK4 protein levels were determined by western blot in 8-paired CSCC tissues (T) and paracancerous tissues (N). GAPDH was used as a loading control. (c) Quantitative analysis of RIPK4 protein levels by western blot was presented as median ± interquartile. (d) RIPK4 immunohistochemical staining in representative cases from each cervical lesion. The scale bar represents 50 μm. (e) Expression of RIPK4 in each cervical lesion based on immunohistochemical scoring, as determined by the percentage of positive cells with strong staining. Values are the median with interquartile range.*P < 0.05 by the Wilcoxon rank-sum test.
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f1: qRT-PCR, western blot and immunohistochemistry analyses of RIPK4.(a) qRT-PCR analysis of RIPK4 mRNA expression in 101 fresh CSCC tissues (T) and 30 paracancerous tissues (N). Expression levels were normalized to those of EFF1A1. (b) RIPK4 protein levels were determined by western blot in 8-paired CSCC tissues (T) and paracancerous tissues (N). GAPDH was used as a loading control. (c) Quantitative analysis of RIPK4 protein levels by western blot was presented as median ± interquartile. (d) RIPK4 immunohistochemical staining in representative cases from each cervical lesion. The scale bar represents 50 μm. (e) Expression of RIPK4 in each cervical lesion based on immunohistochemical scoring, as determined by the percentage of positive cells with strong staining. Values are the median with interquartile range.*P < 0.05 by the Wilcoxon rank-sum test.

Mentions: The mRNA expression of the RIPK4 in 101 CSCC tissues was significantly higher than that of 30 paracancerous samples as determined by qRT-PCR (3.31 ± 1.19 vs. 0.50 ± 1.88, P < 0.001; Fig. 1a). Western blot analysis showed that RIPK4 protein expression was also significantly elevated in 7 of 8 CSCC cases compared with paired paracancerous tissues (P < 0.05; Fig. 1b,c).


Increased RIPK4 expression is associated with progression and poor prognosis in cervical squamous cell carcinoma patients.

Liu DQ, Li FF, Zhang JB, Zhou TJ, Xue WQ, Zheng XH, Chen YB, Liao XY, Zhang L, Zhang SD, Hu YZ, Jia WH - Sci Rep (2015)

qRT-PCR, western blot and immunohistochemistry analyses of RIPK4.(a) qRT-PCR analysis of RIPK4 mRNA expression in 101 fresh CSCC tissues (T) and 30 paracancerous tissues (N). Expression levels were normalized to those of EFF1A1. (b) RIPK4 protein levels were determined by western blot in 8-paired CSCC tissues (T) and paracancerous tissues (N). GAPDH was used as a loading control. (c) Quantitative analysis of RIPK4 protein levels by western blot was presented as median ± interquartile. (d) RIPK4 immunohistochemical staining in representative cases from each cervical lesion. The scale bar represents 50 μm. (e) Expression of RIPK4 in each cervical lesion based on immunohistochemical scoring, as determined by the percentage of positive cells with strong staining. Values are the median with interquartile range.*P < 0.05 by the Wilcoxon rank-sum test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493702&req=5

f1: qRT-PCR, western blot and immunohistochemistry analyses of RIPK4.(a) qRT-PCR analysis of RIPK4 mRNA expression in 101 fresh CSCC tissues (T) and 30 paracancerous tissues (N). Expression levels were normalized to those of EFF1A1. (b) RIPK4 protein levels were determined by western blot in 8-paired CSCC tissues (T) and paracancerous tissues (N). GAPDH was used as a loading control. (c) Quantitative analysis of RIPK4 protein levels by western blot was presented as median ± interquartile. (d) RIPK4 immunohistochemical staining in representative cases from each cervical lesion. The scale bar represents 50 μm. (e) Expression of RIPK4 in each cervical lesion based on immunohistochemical scoring, as determined by the percentage of positive cells with strong staining. Values are the median with interquartile range.*P < 0.05 by the Wilcoxon rank-sum test.
Mentions: The mRNA expression of the RIPK4 in 101 CSCC tissues was significantly higher than that of 30 paracancerous samples as determined by qRT-PCR (3.31 ± 1.19 vs. 0.50 ± 1.88, P < 0.001; Fig. 1a). Western blot analysis showed that RIPK4 protein expression was also significantly elevated in 7 of 8 CSCC cases compared with paired paracancerous tissues (P < 0.05; Fig. 1b,c).

Bottom Line: Further, RIPK4 overexpression was associated with overall (HR = 2.085, P = 0.038) and disease-free survival (HR = 1.742, P = 0.037).Knockdown of RIPK4 reduced cell migration and invasion via inhibition of Vimentin, MMP2 and Fibronectin expression in cervical cancer cells.RIPK4 might act as a potential diagnostic and independent prognostic biomarker for CSCC patients.

View Article: PubMed Central - PubMed

Affiliation: Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.

ABSTRACT
Aberrant expression of receptor interacting protein kinase 4 (RIPK4), a crucial regulatory protein of Wnt/β-catenin signaling, has recently been reported to be involved in several cancers. Here, we report the potential clinical implication and biological functions of RIPK4 in cervical squamous cell carcinoma (CSCC). One hundred and ninety-eight CSCC cases, 109 low-grade squamous intraepithelial lesions (LSILs), 141 high-grade squamous intraepithelial lesions (HSILs) and 63 chronic cervicitis were collected. The expression of RIPK4 was detected by immunohistochemistry (IHC), and its clinical value and oncogenic functions were further assessed. RIPK4 expression increased significantly with disease progression from 3.2% in chronic cervicitis, 19.3% in LSILs and 85.1% in HSILs to 94.4% in CSCCs (P < 0.001). Moreover, RIPK4 may serve as a useful biomarker to distinguish HSIL from chronic cervicitis/LSIL, which are two different clinical types for therapeutic procedures, with a high sensitivity and specificity (85.1% and 86.6%, respectively) and the performance improved when combined with p16(INK4a). Further, RIPK4 overexpression was associated with overall (HR = 2.085, P = 0.038) and disease-free survival (HR = 1.742, P = 0.037). Knockdown of RIPK4 reduced cell migration and invasion via inhibition of Vimentin, MMP2 and Fibronectin expression in cervical cancer cells. RIPK4 might act as a potential diagnostic and independent prognostic biomarker for CSCC patients.

No MeSH data available.


Related in: MedlinePlus