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Overexpression of proteasomal activator PA28α serves as a prognostic factor in oral squamous cell carcinoma.

Feng X, Jiang Y, Xie L, Jiang L, Li J, Sun C, Xu H, Wang R, Zhou M, Zhou Y, Dan H, Wang Z, Ji N, Deng P, Liao G, Geng N, Wang Y, Zhang D, Lin Y, Ye L, Liang X, Li L, Luo G, Feng M, Fang J, Zeng X, Wang Z, Chen Q - J. Exp. Clin. Cancer Res. (2016)

Bottom Line: PA28α was found to be overexpressed in OSCC cell lines and tumor tissues.Specific knockdown of PA28α inhibited OSCC cell proliferation, migration, invasion in vitro and reduced the growth of OSCC xenografts in vivo.These results suggest that PA28α is involved in OSCC oncogenesis and may serve as a potential prognostic factor.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, No. 14, Sec.3, Renminnan Road, Chengdu, Sichuan, 610041, China. fengxiaodong84@126.com.

ABSTRACT

Background: Despite recent advances in oral squamous cell carcinoma (OSCC) diagnosis and therapy, disease recurrence remains common and is strongly associated with mortality. It is therefore critical to identify new targets for both treatment and diagnostic purposes. We aimed at investigating the role of PA28α, a proteasomal activator in OSCC.

Methods: The expression of PA28α was examined in a panel of OSCC cell lines and tissues, associated with oncomine analysis. In a large OSCC patient cohort, the prognostic value of PA28α expression was evaluated. Primary clinical end points were recurrence-free and overall survival rate. Functional involvement of PA28α in OSCC was examined in both in vitro and in vivo models upon specific siRNA knockdown.

Results: PA28α was found to be overexpressed in OSCC cell lines and tumor tissues. High expression of PA28α was significantly associated with recurrence and poorer overall survival. Specific knockdown of PA28α inhibited OSCC cell proliferation, migration, invasion in vitro and reduced the growth of OSCC xenografts in vivo. Multivariate Cox regression analyses revealed PA28α as independent prognostic predictors.

Conclusions: These results suggest that PA28α is involved in OSCC oncogenesis and may serve as a potential prognostic factor.

No MeSH data available.


Related in: MedlinePlus

PA28α may be a discriminator of recurrence and survival in patients with OSCC defined by the Kaplan-Meier curves. a The curves showed that the recurrence in the subtypes divided by PA28α;b The curves showed that the survival in the subtypes divided by PA28α, *P < 0.05, P Values among different PA28α staining values were calculated by the log-rank test
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Fig2: PA28α may be a discriminator of recurrence and survival in patients with OSCC defined by the Kaplan-Meier curves. a The curves showed that the recurrence in the subtypes divided by PA28α;b The curves showed that the survival in the subtypes divided by PA28α, *P < 0.05, P Values among different PA28α staining values were calculated by the log-rank test

Mentions: Tissue slides were prepared from 98 OSCC cases. Those cases exhibiting strong staining (category 2) showed positive recurrence related indexes like higher cumulative recurrence probability (83.3 % vs. 32.9 %) (Additional file 3: Table S2 and Fig. 1c). Recurrence versus non-recurrence of the malignant lesions was considered to be one of the surrogates for clinical outcome of OSCC patients. Inclusion of all well-known factors with prognostic significance in our study would strengthen the utility of PA28α as a prognostic predictor alone or in combination with other factors. In Univariate Cox Regression analysis, PA28α staining (intensity, domain, category), together with smoking, clinical stage, differentiation, T-stage, and lymph node metastasis were all associated with an increased risk of recurrence (Table 1). Kaplan-Meier cumulative recurrence curves related to the above five factors demonstrated significant discrimination ability (Fig. 2 and Additional file 4: Figure S2).Table 1


Overexpression of proteasomal activator PA28α serves as a prognostic factor in oral squamous cell carcinoma.

Feng X, Jiang Y, Xie L, Jiang L, Li J, Sun C, Xu H, Wang R, Zhou M, Zhou Y, Dan H, Wang Z, Ji N, Deng P, Liao G, Geng N, Wang Y, Zhang D, Lin Y, Ye L, Liang X, Li L, Luo G, Feng M, Fang J, Zeng X, Wang Z, Chen Q - J. Exp. Clin. Cancer Res. (2016)

PA28α may be a discriminator of recurrence and survival in patients with OSCC defined by the Kaplan-Meier curves. a The curves showed that the recurrence in the subtypes divided by PA28α;b The curves showed that the survival in the subtypes divided by PA28α, *P < 0.05, P Values among different PA28α staining values were calculated by the log-rank test
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4759779&req=5

Fig2: PA28α may be a discriminator of recurrence and survival in patients with OSCC defined by the Kaplan-Meier curves. a The curves showed that the recurrence in the subtypes divided by PA28α;b The curves showed that the survival in the subtypes divided by PA28α, *P < 0.05, P Values among different PA28α staining values were calculated by the log-rank test
Mentions: Tissue slides were prepared from 98 OSCC cases. Those cases exhibiting strong staining (category 2) showed positive recurrence related indexes like higher cumulative recurrence probability (83.3 % vs. 32.9 %) (Additional file 3: Table S2 and Fig. 1c). Recurrence versus non-recurrence of the malignant lesions was considered to be one of the surrogates for clinical outcome of OSCC patients. Inclusion of all well-known factors with prognostic significance in our study would strengthen the utility of PA28α as a prognostic predictor alone or in combination with other factors. In Univariate Cox Regression analysis, PA28α staining (intensity, domain, category), together with smoking, clinical stage, differentiation, T-stage, and lymph node metastasis were all associated with an increased risk of recurrence (Table 1). Kaplan-Meier cumulative recurrence curves related to the above five factors demonstrated significant discrimination ability (Fig. 2 and Additional file 4: Figure S2).Table 1

Bottom Line: PA28α was found to be overexpressed in OSCC cell lines and tumor tissues.Specific knockdown of PA28α inhibited OSCC cell proliferation, migration, invasion in vitro and reduced the growth of OSCC xenografts in vivo.These results suggest that PA28α is involved in OSCC oncogenesis and may serve as a potential prognostic factor.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, No. 14, Sec.3, Renminnan Road, Chengdu, Sichuan, 610041, China. fengxiaodong84@126.com.

ABSTRACT

Background: Despite recent advances in oral squamous cell carcinoma (OSCC) diagnosis and therapy, disease recurrence remains common and is strongly associated with mortality. It is therefore critical to identify new targets for both treatment and diagnostic purposes. We aimed at investigating the role of PA28α, a proteasomal activator in OSCC.

Methods: The expression of PA28α was examined in a panel of OSCC cell lines and tissues, associated with oncomine analysis. In a large OSCC patient cohort, the prognostic value of PA28α expression was evaluated. Primary clinical end points were recurrence-free and overall survival rate. Functional involvement of PA28α in OSCC was examined in both in vitro and in vivo models upon specific siRNA knockdown.

Results: PA28α was found to be overexpressed in OSCC cell lines and tumor tissues. High expression of PA28α was significantly associated with recurrence and poorer overall survival. Specific knockdown of PA28α inhibited OSCC cell proliferation, migration, invasion in vitro and reduced the growth of OSCC xenografts in vivo. Multivariate Cox regression analyses revealed PA28α as independent prognostic predictors.

Conclusions: These results suggest that PA28α is involved in OSCC oncogenesis and may serve as a potential prognostic factor.

No MeSH data available.


Related in: MedlinePlus