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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

Survival curves for patients with CSCC according to high or low RIPK4 expression.(a) Immunohistochemical staining of RIPK4 in representative squamous cell carcinoma cases with low and high RIPK4 expression, respectively (magnification, 400×). (b) OS curves: 198 patients with low and high expression levels of RIPK4; (c) DFS curves: 198 patients with low and high expression levels of RIPK4. Disease-free survival analysis of RIPK4 expression in patients with (d) stage IB1, (e) LN metastasis or (f) histological grade III.
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f2: Survival curves for patients with CSCC according to high or low RIPK4 expression.(a) Immunohistochemical staining of RIPK4 in representative squamous cell carcinoma cases with low and high RIPK4 expression, respectively (magnification, 400×). (b) OS curves: 198 patients with low and high expression levels of RIPK4; (c) DFS curves: 198 patients with low and high expression levels of RIPK4. Disease-free survival analysis of RIPK4 expression in patients with (d) stage IB1, (e) LN metastasis or (f) histological grade III.

Mentions: Based on the previously described cutoff value, RIPK4 expression in CSCC was separated into low and high groups (Fig. 2a). Low RIPK4 expression (IHC score<6.4) was observed in 47.5% (94 of 198) of CSCC samples, and high RIPK4 expression (≥6.4) was observed in 52.5% (104 of 198) of CSCC samples. The association between the expression of RIPK4 and the clinical significance of CSCC patients was summarized in Table 1. High RIPK4 expression was significantly related to clinical stage (60.7% vs. 46.5% for stage IB2-IIB and IB1; P = 0.048), tumor size (66.7% vs. 47.2% for > 4 cm and ≤4 cm; P = 0.017) and distant metastasis (72.0% vs. 49.7% for + and −; P = 0.037).


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)

Survival curves for patients with CSCC according to high or low RIPK4 expression.(a) Immunohistochemical staining of RIPK4 in representative squamous cell carcinoma cases with low and high RIPK4 expression, respectively (magnification, 400×). (b) OS curves: 198 patients with low and high expression levels of RIPK4; (c) DFS curves: 198 patients with low and high expression levels of RIPK4. Disease-free survival analysis of RIPK4 expression in patients with (d) stage IB1, (e) LN metastasis or (f) histological grade III.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: Survival curves for patients with CSCC according to high or low RIPK4 expression.(a) Immunohistochemical staining of RIPK4 in representative squamous cell carcinoma cases with low and high RIPK4 expression, respectively (magnification, 400×). (b) OS curves: 198 patients with low and high expression levels of RIPK4; (c) DFS curves: 198 patients with low and high expression levels of RIPK4. Disease-free survival analysis of RIPK4 expression in patients with (d) stage IB1, (e) LN metastasis or (f) histological grade III.
Mentions: Based on the previously described cutoff value, RIPK4 expression in CSCC was separated into low and high groups (Fig. 2a). Low RIPK4 expression (IHC score<6.4) was observed in 47.5% (94 of 198) of CSCC samples, and high RIPK4 expression (≥6.4) was observed in 52.5% (104 of 198) of CSCC samples. The association between the expression of RIPK4 and the clinical significance of CSCC patients was summarized in Table 1. High RIPK4 expression was significantly related to clinical stage (60.7% vs. 46.5% for stage IB2-IIB and IB1; P = 0.048), tumor size (66.7% vs. 47.2% for > 4 cm and ≤4 cm; P = 0.017) and distant metastasis (72.0% vs. 49.7% for + and −; P = 0.037).

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