Abstract
BackgroundMultiple protein or microRNA markers have been recognized to contribute to the progression and recurrence of cervical cancers. Particular those, which are associated with the chemo- or radio-resistance of cervical cancers, have been proposed to be promising and to facilitate the definition for cervical cancer treatment options.MethodsThis study was designed to explore the potential prognosis value of p21-activated kinase (PAK)-4 in cervical cancer, via the Kaplan–Meier analysis, log-rank test and Cox regression analysis, and then to investigate the regulatory role of PAK4 in the cisplatin resistance in cervical cancer cells, via the strategies of both PAK4 overexpression and PAK4 knockout.ResultsIt was demonstrated that PAK4 was upregulated in cervical cancer tissues, in an association with the cancer’s malignance variables such as FIGO stage, lymph node or distant metastasis and the poor histological grade. The high PAK4 expression was also independently associated with poor prognosis to cervical cancer patients. Moreover, PAK4 confers cisplatin resistance in cervical cancer Hela or Caski cells. In addition, the PI3K/Akt pathway has been implicated in the PAK4-confered cisplatin resistance. And the PI3K/Akt inhibitor, LY294002, markedly deteriorated the cisplatin-mediated viability reduction of Hela or Caski cells, indicating the involvement of PI3K/Akt pathway in the cisplatin resistance in cervical cancer cells.ConclusionThis study has confirmed the significant prognostic role of PAK4 level in cervical cancer patients and has recognized the regulatory role in cervical cancer progression. Moreover, our study has indicated that PAK4 also confers the chemoresistance of cervical cancer cells in a PI3K/Akt-dependent way. Thus, our study indicates PAK4 as a promising marker for cervical cancer treatment.
Highlights
Multiple protein or microRNA markers have been recognized to contribute to the progression and recurrence of cervical cancers
We re-grouped those samples according to their PAK4 levels as high PAK4 group (n = 43) and low PAK4 group (n = 50), and the unpaired t test indicated a significant difference between the two group (p < 0.0001, Fig. 1b)
High PAK4 expression associates with poor prognosis to cervical cancer patients To recognize the prognostic value of PAK4 expression in patients with cervical cancer, we investigated the association between PAK4 expression and overall survival of cervical cancer patients by Kaplan-Meier analysis and log-rank test
Summary
Multiple protein or microRNA markers have been recognized to contribute to the progression and recurrence of cervical cancers. Particular those, which are associated with the chemo- or radio-resistance of cervical cancers, have been proposed to be promising and to facilitate the definition for cervical cancer treatment options. Multistep processes and molecular markers have been confirmed to be involved in the tumorigenesis, invasiveness of cervical cancers [3]. Since the therapeutic resistance is a common phenomenon in cervical cancers, in patients with advanced, recurrent, and metastatic disease [7]. Biomarkers of proteins [11, 12] and microRNAs [13,14,15], which are associated with the chemo- radio-resistance of cervical cancer have been proposed to be promising and to facilitate the definition for cervical cancer treatment options
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