Prognostic Impact and Therapeutic Potential of CDC20 in Cervical Cancer: Insights from Clinical and Experimental Analyses

doi:10.21203/rs.3.rs-5288572/v1

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Prognostic Impact and Therapeutic Potential of CDC20 in Cervical Cancer: Insights from Clinical and Experimental Analyses

https://doi.org/10.21203/rs.3.rs-5288572/v1

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CDC20 has been identified as an oncogene involved in the development and prognosis of various cancers, yet its role in cervical cancer remains unclear. This study aimed to evaluate CDC20 expression in cervical cancer tissues and its clinical significance. We conducted a retrospective analysis of 249 cervical cancer patients diagnosed at Nanchong Central Hospital from January to December 2022. Immunohistochemistry was used to assess CDC20 expression, and statistical methods compared clinicopathological characteristics. Survival analysis employed the Kaplan-Meier method, and Cox regression identified survival risk factors. Additionally, siRNA was used to knock down CDC20 in HeLa cells to examine its effects on proliferation, invasion, and migration. Results indicated that CDC20 expression was significantly higher in cervical cancer tissues (61.85%) compared to adjacent normal tissues (7.5%) (p < 0.05). High CDC20 expression was associated with poorer overall survival, particularly in specific subgroups (p < 0.05) and identified as an independent risk factor (p < 0.05). Silencing CDC20 inhibited cancer cell proliferation and invasion, while xenograft models demonstrated reduced tumor growth with CDC20 inhibition (p < 0.01). CDC20 may serve as a valuable prognostic biomarker and therapeutic target for cervical cancer.

cervical cancer

CDC20

clinicopathological characteristics

prognosis

risk factors

proliferation

Cervical cancer is a serious health issue, and understanding the factors that affect its progression is important for improving patient outcomes. CDC20 is a protein that has been linked to the development and drug resistance of many cancers, but its role in cervical cancer is not well understood. In this study, we analyzed the levels of CDC20 in cervical cancer tissues and examined its relationship with patient outcomes and tumor characteristics. We also tested how reducing CDC20 levels affected the growth and spread of cervical cancer cells in the lab. Our findings suggest that CDC20 may play a key role in cervical cancer progression and could be used as a marker to predict patient survival. This research could lead to better ways to identify high-risk patients and develop new treatments for cervical cancer.

Cervical cancer (CC) remains one of the leading causes of cancer-related mortality in women worldwide, particularly in developing countries[1]. Despite advancements in screening programs and treatment modalities, the prognosis for patients with advanced or recurrent CC remains poor, necessitating the identification of novel biomarkers and therapeutic targets to improve outcomes[2]. In recent years, growing attention has been directed toward understanding the molecular mechanisms underlying CC progression and identifying factors that could serve both as prognostic indicators and potential therapeutic targets.

Cell Division Cycle 20 (CDC20) is a well-characterized regulator of the cell cycle, particularly during the transition from metaphase to anaphase in mitosis[3]. CDC20 has been implicated in the progression of several cancers, where its overexpression is often correlated with poor prognosis and enhanced tumor aggressiveness[4]. Besides, CDC20 can regulate tumor sensitivity to therapy. For example, CDC20 as a key regulator of GSDME-mediated pyroptosis, offered new molecular targets to enhance anti-PD1 immunotherapy[5]. CDC20 also can enhanced prostate cancer radioresistance by upregulating Twist1 expression, offering an effective way to improve the adiosensitivity[6]. Silencing CDC20 inhibited the growth of metastatic castration-resistant prostate cancer and increases chemosensitivity to docetaxel by modulating Wnt/β-catenin signaling[7]. The role of CDC20 in promoting the proliferation, migration, and invasion of malignant tumor cells has been confirmed in several studies[8, 9]. However, its role in cervical cancer remains inadequately explored. Several studies have suggested that CDC20 may influence tumor growth and metastasis through its impact on key biological processes, such as cell proliferation, invasion, and migration, but comprehensive analyses in cervical cancer populations are lacking[10, 11].

This study aims to bridge this gap by investigating the expression of CDC20 in cervical cancer tissues and evaluating its association with clinicopathological characteristics and patient outcomes. Additionally, we explore the biological functions of CDC20 in cervical cancer cells, including its impact on proliferation, invasion, and migration, through both in vitro assays and in vivo xenograft models. By elucidating the role of CDC20 in cervical cancer, we seek to provide insight into its potential as a prognostic biomarker and therapeutic target, ultimately contributing to the development of more effective treatment strategies for this malignancy.

2.1 Patients

Cervical cancer patients treated at Nanchong Central Hospital from January 2020 and December 2022 were selected. All cases were confirmed through pathological assessment. Clinical data collected encompassed patient age, time of diagnosis, time of treatment initiation, maximum tumor diameter, number of primary tumor sites, tumor stage, treatment regimen, pathological type, histopathological grade, and overall survival (OS). Follow-up was conducted through outpatient visits or telephone consultations. Survival time was calculated from the date of diagnosis to July 2024 or the time of patient death.

Inclusion criteria were as follows: (1) age ≥ 18 years; (2) sufficient pathological specimens available for immunohistochemistry; and (3) the clinical data to be collected is complete. Exclusion criteria included: (1) death due to non-cancer-related causes during follow-up; and (2) loss to follow-up.

2.2 Cervical cancer cell lines

The cervical cancer cell lines HeLa, HeLa 229, and C-33A were obtained from the Cell Bank of the Chinese Academy of Sciences. HeLa and C-33A cells were cultured in 90% Gibco DMEM supplemented with 10% Gibco fetal bovine serum (FBS). In contrast, HeLa 229 cells were maintained in 90% RPMI 1640 medium with 10% Gibco FBS. All cell lines were incubated at 37°C in a humidified atmosphere containing 5% CO₂.

2.3 Immunohistochemistry

CDC20 expression in tissue samples was evaluated through immunohistochemistry. All specimens were fixed in 10% neutral formalin, embedded in paraffin, and sectioned. After routine hematoxylin and eosin (HE) staining, immunohistochemical staining was performed using the EnVision method with DAB as the chromogen. The CDC20 antibody (Hua'an, Hangzhou) was diluted at a ratio of 1:100. Expression levels were assessed using a standard scoring system commonly applied in similar studies [12].

The scoring system for the percentage of positive cells was as follows: 0 points for 0%, 1 point for 1–10%, 2 points for 11–50%, and 3 points for 51–100%. Staining intensity was scored as: 0 points for negative, 1 point for weak positive, 2 points for moderate positive, and 3 points for strong positive. The total score was obtained by multiplying these two scores, with a score of ≤ 3 indicating low expression and ≥ 4 indicating high expression.

2.4 qRT-PCR

Cell samples were collected, and total RNA was extracted using the TRIzol method. The concentration and purity of the RNA were assessed using the A260/A280 ratio. Complementary DNA (cDNA) was synthesized through reverse transcription using primers obtained from Sangon Biotech (Shanghai); the primer sequences are detailed in Supplementary Table 1. PCR amplification was conducted using a Takara Bio kit, and the relative expression levels of the target genes were calculated using the ΔΔCt method, normalizing to the internal reference gene GAPDH..

2.5 siRNA transfection

When the cells reached 80% confluence, siRNA was prepared for transfection by mixing it with the transfection reagent HpoTrans. The mixture was gently agitated and allowed to stand for 5–20 minutes to facilitate complex formation. Subsequently, the complexes were added to the cell culture dishes and gently swirled to ensure uniform distribution. The transfected cells were incubated at 37°C in a humidified atmosphere with 5% CO₂ for an additional 24–72 hours prior to sample collection. The interfering RNA was designed and synthesized by Jikai Biological Company, with the sequences provided in Supplementary Table 2.

2.6 Colony formation assay

The colony formation assay was performed to evaluate the proliferative capacity of cervical cancer cells. Briefly, cells were seeded into 6-well plates at a density of 500 cells per well and cultured for 10–14 days under standard conditions. Once visible colonies had formed, the cells were fixed with 4% paraformaldehyde for 15 minutes and then stained with 0.1% crystal violet for 30 minutes. Colonies containing more than 50 cells were counted under a microscope. The experiment was repeated in triplicate for each group.

2.7 Wounding healing assay

Target cells were seeded in a culture dish at a uniform density and allowed to reach approximately 90% confluence. A uniform scratch was then made across the cell layer using a 1 mL pipette tip. The dish was rinsed to remove debris, and fresh culture medium was added. The healing process of the scratch was observed and recorded at specific time points using a microscope. The width of the scratch was measured, and the cell migration rate was calculated to evaluate the healing capacity of the cells.

2.8 Transwell assay

Target cells were seeded in the upper chamber of a Transwell insert and cultured until they reached the logarithmic growth phase. The lower chamber was filled with medium containing appropriate chemotactic factors to induce cell migration. After a specified incubation period, non-migrated cells in the upper chamber were gently removed with a cotton swab. The migrated cells in the lower chamber were then fixed with methanol and stained with crystal violet. Finally, the number of cells in the lower chamber was observed and counted to assess their migratory capacity.

2.9 Animal experimentation

Cells were cultured in vitro until they reached the logarithmic growth phase, then harvested and resuspended in saline to achieve a concentration of 1 × 10⁶ cells/mL. Using sterile techniques, the cell suspension was injected subcutaneously into the dorsal region of BALB/c nude mice, with a typical injection volume of 100 µL. Post-operative observations were conducted regularly to monitor tumor growth, recording changes in tumor size and body weight. Treatment began one week post-surgery, administering the CDC20 inhibitor Apcin at a dosage of 20 mg/kg every other day and cisplatin (DDP) at 5 mg/kg once a week. This treatment regimen continued for two weeks before drug administration was discontinued, after which the tumors were excised for further analysis.

2.10 Statistical methods

Statistical analyses were performed using SPSS version 26.0. Clinical characteristics and cross-tabulated data between the high and low CDC20 expression groups were compared using the χ² test. Survival curves were generated utilizing the Kaplan-Meier method, with inter-group comparisons conducted via the log-rank test. Prognostic risk factors were assessed using the Cox proportional hazards regression model. One-way analysis of variance (ANOVA) was employed to compare in vivo tumor growth rates. A p-value of < 0.05 was deemed statistically significant.

3.1 The expression of CDC20 in cervical cancer and its relationship with clinical pathological features of cervical cancer.

A total of 249 cervical cancer patients with available pathological specimens were included in this study, along with 80 matched adjacent non-cancerous tissue samples. Among the cohort of 249 cervical cancer tissues, high CDC20 expression was observed in 61.85% of cases (154/249), compared to only 7.5% (6/80) in adjacent non-cancerous tissues (χ² = 71.587, p < 0.001), as illustrated in Fig. 1. Chi-square tests revealed a significant association between high CDC20 expression and various clinical parameters, including tumor size, T stage, local lymph node metastasis (N stage), FIGO stage, pathological type, and histological grade, with all comparisons demonstrating statistically significant differences (p < 0.05) (Table 1).

Table 1

Correlation of CDC20 with clinicopathological characteristics
Charateristics	N	High CDC20 (n = 154)	Low CDC20 (n = 95)	χ²	P value
Age
< 60	150	92	58	0.042	0.837
≥ 60	99	62	37
Number of tumor
1	227	142	85	0.545	0.46
≥ 2	22	12	10
Size of tumor
≤ 16mm	141	46	95	117.654	0.000
> 16mm	108	108	0
T stage
T1	138	61	77	42.747	0.000
T2	70	62	8
T3	34	26	8
T4	7	5	2
N stage
N0	69	60	9	25.503	0.000
N1-2	170	94	86
M stage
M0	237	144	93	2.467	0.116
M1	12	10	2
FIGO stage
I	128	54	74	45.432	0.000
II	63	56	7
III	39	29	10
IV	19	15	4
Histologic type
Squamous	162	108	54	9.447	0.024
Adenocarcinoma	63	29	34
Adenoid cystic	16	12	4
Adenosquamous	8	5	3
Grade pathological
1	42	12	30	32.962	0.000
2	144	89	55
3	63	53	10

3.2 The impact of CDC20 expression on the OS of cervical cancer patients

During the follow-up period, 22 out of 154 cervical cancer patients with high CDC20 expression (14.29%) died, which was significantly higher than the mortality rate observed in the low expression group (8 out of 95, 8.42%). The difference in mortality between the two groups was statistically significant, as determined by the Log-rank test (χ² = 36.743, p < 0.001) (Fig. 2). These findings suggest that high CDC20 expression is associated with poor overall survival (OS) in cervical cancer patients.

A subgroup analysis was conducted based on clinical stage, histological type, and pathological grade to further evaluate the prognostic value of CDC20 expression across different subgroups. The results indicated that high CDC20 expression was significantly associated with shorter survival in patients with stages I, II, and IV cervical cancer (p < 0.05). Although stage III patients with low CDC20 expression demonstrated longer survival compared to those with high expression, this difference did not reach statistical significance (p = 0.062) (Table 2). Significant differences in overall survival (OS) were observed between high and low CDC20 expression groups in both squamous cell carcinoma and adenocarcinoma (p < 0.05) (Fig. 3). In patients with grade 1 tumors, CDC20 expression did not significantly impact survival (p = 0.086). However, in grade 2 (p = 0.027) and grade 3 (p = 0.000) tumors, low CDC20 expression was associated with improved OS (Fig. 4). These findings suggest that CDC20 expression is a significant prognostic factor for OS in cervical cancer patients, varying across different clinical stages, histological subtypes, and pathological grades.

Table 2

The impact of high CDC20 expression on the survival of cervical cancer patients at different stages.
Stage	N	High CDC20 group (months)		Low CDC20 group (months)		χ²	P
Stage	N	OS(mean)	95%CI	OS(mean)	95%CI	χ²	P
All cases	249	42.54	42.126–42.782	44.865	44.539–45.191	36.743	0.000
Stage I	128	45.376	45.165–45.587	45.766	45.478–46.054	5.081	0.024
Stage II	63	40.165	39.157–41.678	-	-	23.559	0.000
Stage III	39	36.814	35.552–38.076	41.217	39.902–42.533	3.479	0.062
Stage IV	19	24.018	21.733–26.303	36.04	34.725–37.355	4.477	0.034

-: No deaths occurred in this group; OS: Overall survival; CI: Confidence interval.

3.3 The impact of CDC20 expression on the survival of patients undergoing different treatment regimens.

The enrolled patients primarily received treatment modalities that included surgery combined with radiotherapy or radiotherapy combined with chemotherapy. Cervical cancer patients with high CDC20 expression demonstrated slightly longer survival following treatment with the surgical sequential radiotherapy regimen compared to those in the low expression group (χ² = 19.922, p < 0.001). In contrast, CDC20 expression did not significantly impact survival in patients receiving combined radiotherapy and chemotherapy (χ² = 0.697, p = 0.404) (Fig. 5). These results indicate that patients with high CDC20 expression derived greater survival benefits from the treatment regimen of surgical resection combined with radiotherapy.

3.4 Analysis of risk factors affecting survival in cervical cancer patients.

To assess whether CDC20 is an independent prognostic factor for overall survival (OS) in cervical cancer patients, we conducted Cox regression analyses. The univariate Cox analysis identified several clinical and pathological factors associated with poorer OS, including high CDC20 expression, age over 60 years, tumor diameter exceeding 16 mm, absence of surgical resection combined with radiotherapy, lack of radiotherapy or chemotherapy, a delay of more than 10.5 days from diagnosis to treatment, T3-4 classification, regional lymph node metastasis, distant metastasis, and pathological grades of 2–3 (p < 0.05) (Table 3). Based on the clinically significant factors identified in the univariate analysis, we constructed a multivariate Cox proportional hazards model. The results revealed that high CDC20 expression, age ≥ 60 years, tumor diameter > 16 mm, absence of radiotherapy, a delay of > 10.5 days from diagnosis to treatment, T3-4 classification, regional lymph node metastasis, distant metastasis, and FIGO stages 3–4 were independent risk factors impacting OS in cervical cancer patients (p < 0.05) (Table 3).

Table 3

Univariate and multivariate analysis of factors influencing mortality after treatment in cervical cancer patients.
Factors	Univariate analysis			Multivariate analysis
Factors	HR	95%CI	P	HR	95%CI	P
High CDC20	1.745	1.453–2.097	0.000	6.803	3.745–12.346	0.000
Age ≥ 60	1.472	1.235–1.754	0.000	1.431	1.153–1.773	0.001
Number of tumor ≥ 2	1.123	0.865–1.457	0.383
Size of tumor>16mm	3.599	3.005–4.309	0.000	7.610	4.225–13.709	0.000
Surgery only	2.466	2.072–2.935	0.000	1.250	0.979–1.595	0.073
Without radiotherapy	10.641	7.818–14.483	0.000	5.956	3.654–9.707	0.000
Without chemotherapy	7.052	5.557–8.950	0.000	1.327	0.954–1.845	0.093
Over 10.5days from diagnosis to treatment	1.927	1.614–2.302	0.000	9.259	1.144–1.748	0.001
T3-4	4.424	3.745–5.226	0.000	3.937	1.153–3.125	0.012
N+	4.251	3.592–5.030	0.000	1.505	1.224–1.851	0.000
M1	4.118	3.213–5.278	0.000	4.348	1.021–2.519	0.04
FIGO stage III-IV	5.393	4.568–6.367	0.000	4.022	2.399–6.745	0.000
Non-adenocarcinoma	0.940	0.790–1.119	0.489
Grade 2–3	3.02	2.164–4.215	0.000	1.401	0.980–2.003	0.064

HR: Hazard Ratio; CI: Confidence interval.

3.5 Expression of CDC20 in cervical cancer cell lines and validation of effects following siRNA transfection.

Cervical cancer cell lines (HeLa, HeLa 229, and C-33A) were selected for cellular experiments, and baseline detection was performed using qRT-PCR. The results indicated that CDC20 expression was highest in HeLa cells (F = 306.1, p < 0.0001) (Fig. 6A). Therefore, HeLa cells were chosen for CDC20 gene knockdown. HeLa cells were transfected with siRNA targeting the CDC20 gene, and qRT-PCR validation demonstrated that siRNA-1 achieved the most effective silencing, followed by siRNA-2 and siRNA-3 (Fig. 6B). Consequently, siRNA-1 was selected for transfection in subsequent experiments with HeLa cells.

3.6 Silencing of CDC20 can inhibit the proliferation, migration, and invasion of cervical cancer cells..

The effects of CDC20 knockdown on HeLa cell proliferation were validated through colony formation assays, which included a blank control group, a negative control group, and a CDC20 knockdown group. The results demonstrated that cell proliferation in the CDC20 knockdown group was significantly lower than that in the control group (Fig. 7A), indicating a positive correlation between CDC20 expression and cervical cancer cell proliferation. In the Transwell assay, the number of cells that penetrated the Matrigel in the CDC20 knockdown group was significantly lower than that in the control group (Fig. 7B), indicating that CDC20 plays a role in promoting the invasive ability of cervical cancer cells. Additionally, in the scratch wound healing assay, the wound healing area in the CDC20 knockdown group was significantly smaller than that in the control group at the same time point (Fig. 7C), further confirming that CDC20 enhances the migratory capability of cervical cancer cells.

3.7 The CDC20 inhibitor suppresses cervical cancer cell growth in vivo and enhances the antitumor effect of cisplatin.

A xenograft subcutaneous tumor model was established in BALB/c nude mice using HeLa cells, with four groups: control group, Apcin (CDC20 inhibitor) monotherapy group, cisplatin (DDP) monotherapy group, and Apcin combined with DDP group. The results demonstrated that the tumor volume of the Apcin + DDP group, Apcin group, DDP group, and control group were 3.2 mm³, 8.12 mm³, 6.21 mm³, and 10.42 mm³, respectively (p < 0.01). These findings indicated that Apcin combined with DDP synergistically enhances the inhibition of cervical cancer cell proliferation in vivo. While Apcin alone can suppress tumor growth, its efficacy is slightly lower than that of DDP (Fig. 8).

The most common histological types of cervical cancer include squamous cell carcinoma (70–90%), adenocarcinoma (10–20%), and adenosquamous carcinoma[13]. With the widespread adoption of cervical cancer screening and the early onset of symptoms, such as abnormal bleeding, most patients are diagnosed at an early stage, predominantly stages I-IIA. Consequently, the overall long-term survival rate for cervical cancer patients remains relatively high, at approximately 66–70%, with 5-year survival rates for early-stage patients exceeding 90%[13]. Standard treatment for patients in stages I-IIA primarily involves surgery, followed by adjuvant radiotherapy or chemotherapy depending on the presence of risk factors. For patients in stages IIB-IVA, concurrent chemoradiotherapy is the preferred approach[2]. In this study, 249 patients were included, with approximately 65% diagnosed with squamous cell carcinoma, and 93.5% in stages I-II. The overall 5-year survival rate was 88%, with the main treatment regimens consisting of surgical resection followed by radiotherapy, or a combination of radiotherapy and chemotherapy. These findings align with previously reported clinical and pathological characteristics of cervical cancer.

As a member of the cell division cycle (CDC) protein family, CDC20 plays a crucial role in regulating cell division by interacting with specific substrate motifs, including the A-box, D-box, and KEN-box[14]. In recent years, CDC20 overexpression has been observed in a variety of human cancers, where it has been associated with poor prognosis. For instance, CDC20 is highly expressed in non-small cell lung cancer (NSCLC), identifying it as an independent prognostic factor for the disease[12]. Elevated CDC20 levels in urothelial bladder carcinoma (UBC) were correlated with shorter recurrence-free survival and poorer overall survival[15]. Similarly, a significant association was reported between high CDC20 expression and poor prognosis in breast cancer, suggesting that CDC20 could be a valuable therapeutic target for this malignancy[16]. This oncogenic role of CDC20 has been implicated in numerous other cancers, including pancreatic, colorectal, ovarian, and hepatocellular carcinomas[17–19]. Moreover, Ana et al. highlighted the overexpression of CDC20 in cervical cancer through bioinformatics analysis[10]. Our findings aligned with those researches, confirming that CDC20 was significantly overexpressed in cervical cancer tissues compared to normal tissues. This overexpression may be linked to a dysfunctional spindle assembly checkpoint[20]. Prior studies have also shown that elevated CDC20 expression correlates with unfavorable pathological features, including poor tumor differentiation, larger tumor size, lymph node metastasis, distant metastasis, and advanced tumor stage [24–26]. In this study, we observed that high CDC20 expression was significantly associated with larger tumor diameters, advanced T stage, local lymph node metastasis, advanced FIGO stage, pathological type, and pathological grade in cervical cancer patients, consistent with the correlation between CDC20 expression and pathological features in other malignancies. Furthermore, this study also demonstrated that high CDC20 expression negatively impacted overall survival (OS) in cervical cancer patients, with CDC20 acting as an independent prognostic factor for mortality. Previous research has established that CDC20 facilitates the proliferation and invasion of hepatocellular carcinoma (HCC), breast cancer, gastric cancer, and pancreatic cancer cells[8, 21–23]. Consistent with these observations, our in vitro experiments revealed that CDC20 similarly promotes the proliferation, migration, and invasion of cervical cancer cells. Thus, CDC20 may contribute to poorer patient outcomes by enhancing tumor cell growth and metastasis in vivo.

Subgroup analysis revealed that high CDC20 expression was associated with decreased survival in patients with stage I, II, and IV disease. Although patients with stage III and low CDC20 expression exhibited better OS than those with high expression, the difference was not statistically significant, potentially due to the limited number of stage III cases in our cohort, necessitating further investigation in larger cohorts. Besides, CDC20 expression had a significant effect on OS in patients with grade 2 and grade 3 tumors, with the low-expression group showing better prognosis. However, no significant difference in OS was observed between high and low CDC20 expression in grade 1 tumors, possibly due to the lower malignancy of grade 1 tumors[24]. Further in-depth experimental studies are required to elucidate the correlation between CDC20 expression and tumor grade.

Additionally, to assess the effect of CDC20 expression on survival in patients undergoing different treatment modalities, we conducted another subgroup analysis. The results indicated that high CDC20 expression adversely affected the prognosis of patients who underwent surgery combined with radiotherapy, but did not influence the survival of patients treated with chemoradiotherapy. This may be attributable to the fact that chemoradiotherapy is primarily administered to patients with locally advanced disease, where the advanced stage itself may have a more pronounced impact on survival outcomes than CDC20 expression[25]. These findings suggest that patients with low CDC20 expression may experience better survival outcomes when treated with surgery combined with radiotherapy. Furthermore, animal studies revealed that combining a CDC20 inhibitor with chemotherapy resulted in synergistic antitumor effects, indicating that CDC20 may play a role in modulating chemotherapy sensitivity. This observation aligns with findings from other studies, which have demonstrated that CDC20 promoted chemoresistance in esophageal cancer via regulation of E2F1[26], while its downregulation enhances cisplatin sensitivity in osteosarcoma[27]. Additionally, CDC20 has been shown to promote radiotherapy resistance in prostate cancer through activation of Twist1, and its silencing increases sensitivity to docetaxel[6, 7]. Moreover, CDC20 has been implicated in driving endocrine therapy resistance in estrogen receptor-positive breast cancer[28]. Therefore, CDC20 overexpression-induced therapy resistance may also contribute to poor OS in affected patients.

These findings suggest that CDC20 expression, in combination with the previously identified risk factors, could be utilized to assess prognosis and inform the development of personalized treatment strategies for cervical cancer patients, with the goal of improving survival outcomes. However, this study has certain limitations, including a relatively small sample size, lack of multi-center validation, and the absence of an evaluation of CDC20's impact on disease-free survival or progression-free survival following different treatment modalities. Future large-scale, multi-center clinical trials are necessary to validate these results. Furthermore, both in vitro and in vivo experiments have demonstrated that CDC20 gene silencing inhibits cervical cancer cell proliferation, underscoring the need for further investigation into the molecular mechanisms by which CDC20 regulates cervical cancer cell growth.

In summary, CDC20 is significantly overexpressed in cervical cancer, with elevated CDC20 expression serving as an independent predictor of poor prognosis in affected patients. Moreover, patients with high CDC20 expression are more likely to benefit from surgical intervention followed by radiotherapy. Consequently, CDC20 holds potential as a predictive biomarker for both diagnosis and prognosis in cervical cancer, as well as a valuable reference for guiding treatment plan selection.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki, and approved by Ethics Committee of Neijiang Second People’s Hospital (2024RP-806-05, August 6, 2024).

Informed Consent Statement
Due to the retrospective nature of this study and the fact that no personal patient information will be disclosed, and patient participation is not required, the Ethics Committee of Neijiang Second People's Hospital approved the waiver of informed consent.

Conflicts of Interest:

The authors declare no conflicts of interest.

Funding:

This research was funded by the Natural Science Foundation of Sichuan (No. 23ZDYF1517), the Science and Technology Project of Nanchong (No. 22SXQT0066), and the Medical Science and Technology project of Health Commission of Sichuan Province (21PJ194).

Author Contribution

Conceptualization, F.X. and GH.X.; methodology, F.X.; software, F.X.; validation, F.X., Q.Z. and GJ.Z.; formal analysis, F.X.; investigation, F.X.; resources, F.X. and Q.Z.; data curation, F.X. and J.B.; writing—original draft preparation, F.X.; writing—review and editing, F.X. and GJ.Z.; visualization, F.X.; supervision, J.B. and G.H.X.; project administration, G.H.X.; funding acquisition, F.X. and J.B. All authors have read and agreed to the published version of the manuscript.

Acknowledgments:

We sincerely thank Zhendong Li from Neijiang Second People's Hospital for providing valuable data support for this experiment, and Chun Huang from Sichuan Cancer Hospital from providing animal laboratory.

Data Availability Statement:

The original contributions presented in the study are included in the article and supplementary material, further inquiries can be directed to the corresponding author.

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You are reading this latest preprint version

Prognostic Impact and Therapeutic Potential of CDC20 in Cervical Cancer: Insights from Clinical and Experimental Analyses

Status:

Version 1

Abstract

Figures

Simple Summary

1. Introduction

2. Materials and Methods

2.1 Patients

2.2 Cervical cancer cell lines

2.3 Immunohistochemistry

2.4 qRT-PCR

2.5 siRNA transfection

2.6 Colony formation assay

2.7 Wounding healing assay

2.8 Transwell assay

2.9 Animal experimentation

2.10 Statistical methods

3. Results

3.2 The impact of CDC20 expression on the OS of cervical cancer patients

3.3 The impact of CDC20 expression on the survival of patients undergoing different treatment regimens.

3.4 Analysis of risk factors affecting survival in cervical cancer patients.

3.5 Expression of CDC20 in cervical cancer cell lines and validation of effects following siRNA transfection.

3.6 Silencing of CDC20 can inhibit the proliferation, migration, and invasion of cervical cancer cells..

4. Discussion

5. Conclusion

Declarations

Institutional Review Board Statement

Informed Consent Statement
Due to the retrospective nature of this study and the fact that no personal patient information will be disclosed, and patient participation is not required, the Ethics Committee of Neijiang Second People's Hospital approved the waiver of informed consent.

Conflicts of Interest:

Funding:

Author Contribution

Acknowledgments:

Data Availability Statement:

References

Additional Declarations

Supplementary Files

Status:

Version 1

Prognostic Impact and Therapeutic Potential of CDC20 in Cervical Cancer: Insights from Clinical and Experimental Analyses

Status:

Version 1

Abstract

Figures

Simple Summary

1. Introduction

2. Materials and Methods

2.1 Patients

2.2 Cervical cancer cell lines

2.3 Immunohistochemistry

2.4 qRT-PCR

2.5 siRNA transfection

2.6 Colony formation assay

2.7 Wounding healing assay

2.8 Transwell assay

2.9 Animal experimentation

2.10 Statistical methods

3. Results

3.2 The impact of CDC20 expression on the OS of cervical cancer patients

3.3 The impact of CDC20 expression on the survival of patients undergoing different treatment regimens.

3.4 Analysis of risk factors affecting survival in cervical cancer patients.

3.5 Expression of CDC20 in cervical cancer cell lines and validation of effects following siRNA transfection.

3.6 Silencing of CDC20 can inhibit the proliferation, migration, and invasion of cervical cancer cells..

4. Discussion

5. Conclusion

Declarations

Institutional Review Board Statement

Informed Consent Statement Due to the retrospective nature of this study and the fact that no personal patient information will be disclosed, and patient participation is not required, the Ethics Committee of Neijiang Second People's Hospital approved the waiver of informed consent.

Conflicts of Interest:

Funding:

Author Contribution

Acknowledgments:

Data Availability Statement:

References

Additional Declarations

Supplementary Files

Status:

Version 1

Informed Consent Statement
Due to the retrospective nature of this study and the fact that no personal patient information will be disclosed, and patient participation is not required, the Ethics Committee of Neijiang Second People's Hospital approved the waiver of informed consent.