Abstract
BackgroundCervical cancer is the most fatal gynecological carcinoma in the world. It is urgent to explore novel prognostic biomarkers and intervention targets for cervical cancer.MethodsThrough integrated quantitative proteomic strategy, we investigated the protein expression profiles of cervical cancer; 28 fresh frozen tissue samples (11 adenocarcinoma (AC), 12 squamous cell carcinoma (SCC) and 5 normal cervixes (HC)) were included in discover cohort; 45 fresh frozen tissue samples (19 AC, 18 SCC and 8 HC) were included in verification cohort; 140 paraffin-embedded tissues samples of cervical cancer (85 AC and 55 SCC) were used for immunohistochemical evaluation (IHC) of coatomer protein subunit alpha (COPA) as a prognostic biomarker for cervical cancer; how deficiency of COPA affects cell viability and tumorigenic ability of cervical cancer cells (SiHa cells and HeLa cells) were evaluated by cell counting kit-8 and clone formation in vitro.ResultsWe identified COPA is a potential prognostic biomarker for cervical cancer in quantitative proteomics analysis. By retrospective IHC analysis, we additionally verified the proteomics results and demonstrated moderate or strong IHC staining for COPA is an unfavourable independent prognostic factor for cervical cancer. We also identified COPA is a potential pharmacological intervention target of cervical cancer by a series of in vitro experiments.ConclusionThis study is the first to demonstrate that COPA may contribute to progression of cervical cancer. It can serve as a potential prognostic biomarker and promising intervention target for cervical cancer.
Highlights
Cervical cancer is the most fatal gynecological carcinoma worldwide [1]
We found that all tissues of AC (Figs. 5G) and most tissues of SCC (Figs. 5H) with stage II and above tumors were strongly positive stained of coatomer protein subunit alpha (COPA), while a considerable number of tissues from patients with stage I cervical cancer were weakly stained for COPA
Validation of COPA staining can serve as an independent prognostic factor for cervical cancer Through a survival analysis, we discovered that the patients with the moderate or strong COPA staining possessed worse survival than the patients with the negative or weak COPA staining (p = 0.0033) (Fig. 7A)
Summary
Cervical cancer is the most fatal gynecological carcinoma worldwide [1]. Diagnosis and accurate prediction of prognosis are essential for guiding the clinical treatment [2]. Incidence rate of cervical cancer is rising steadily [6,7,8]. There has been no significant improvement in treatment strategies for cervical cancer in the last decades. This brings forward the urgent need for further exploring prognostic biomarkers and innovative therapies to improve the prognosis of patients with cervical cancer. Cervical cancer is the most fatal gynecological carcinoma in the world. It is urgent to explore novel prognostic biomarkers and intervention targets for cervical cancer
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