The role and contribution of treatment and imaging modalities in global cervical cancer management: survival estimates from a simulation-based analysis

Ward, Zachary J.; Grover, Surbhi; Scott, Andrew; Woo, Sungmin; Salama, Dina H.; Jones, Elizabeth; El-Diasty, Tarek; Pieters, Bradley R.; Trimble, Edward L.; Vargas, Herbert Alberto; Hricak, Hedvig; Atun, Rifat

doi:10.1016/s1470-2045(20)30316-8

Cited by 37 publications

(23 citation statements)

References 25 publications

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“…Cervical cancer ranks fourth in the global incidence of female tumors. Despite continuous improvements in traditional treatment methods, cervical cancer causes more than 300, 000 deaths worldwide each year [1]. It is well known that the development of cervical cancer is a multi-step carcinogenic process, which is a consequence of the activation of multiple oncogenes and the inactivation of tumor suppressor genes [2].…”

Section: Introductionmentioning

confidence: 99%

ZBTB28 induces autophagy by regulation of FIP200 and Bcl-XL facilitating cervical cancer cell apoptosis

Gong

et al. 2021

J Exp Clin Cancer Res

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Background Among the common preventable cancers of women, cervical cancer has the highest morbidity. It is curable if detected at an early stage. However, reliable diagnostic and prognostic markers, which relate to physiologic and pathologic regulation of cervical cancer, are not available. In this study, one such potential marker, ZBTB28, was evaluated for its potential usefulness in cervical cancer assessment. Methods Public database analysis, reverse-transcription polymerase chain reaction (PCR), and methylation-specific PCR were employed to analyze ZBTB28 expression and promoter methylation. The importance of ZBTB28 in cervical cancer cells was assessed by cellular and molecular analysis in vitro and in vivo. Results This study assessed the anti-tumor effects of the transcription factor, ZBTB28, which is often silenced in cervical cancer due to CpG methylation of its promoter. We found ZBTB28 to directly affect cervical cancer cell proliferation, apoptosis, autophagy, and tumorigenesis. Also, it increased cancer cell chemosensitivity to Paclitaxel, Cisplatin, and 5-fluorouracil. Ectopic ZBTB28 expression inhibited the growth of cervical cancer xenografts in nude mice. Furthermore, electron microscopy demonstrated ZBTB28 to induce autophagosomes in cervical cancer cells. ZBTB28 induced cellular autophagy by the degradation of Bcl-XL, reduction of the Bcl-XL-BECN1 complex, and by interaction with the autophagy-related gene FIP200. ZBTB28-induced autophagy of cervical cancer cells was shown to mediate cellular apoptosis through the regulation of FIP200. Conclusion These findings identify ZBTB28 as a tumor suppressor gene that can induce autophagy-related apoptosis in cervical cancer cells. As such, ZBTB28 may be a target for the treatment of uterine-cervical carcinoma. Further, ZBTB28 promoter methylation analysis may offer a new objective strategy for cervical cancer screening.

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Section: Introductionmentioning

confidence: 99%

ZBTB28 induces autophagy by regulation of FIP200 and Bcl-XL facilitating cervical cancer cell apoptosis

Gong

et al. 2021

J Exp Clin Cancer Res

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“…Cervical cancer is a common female malignancy worldwide, with nearly 600,000 cases and more than 300,000 deaths every year. 1 The mortality rate in developed countries is lower than in developing countries because of the successful cytological screening and high rate of prophylactic human papillomavirus (HPV) vaccination in developed countries. 1,2 An estimated 14,480 patients will be diagnosed and an estimated 4,290 females will die from cervical cancer in the United States in 2021.…”

Section: Introductionmentioning

confidence: 99%

“…1 The mortality rate in developed countries is lower than in developing countries because of the successful cytological screening and high rate of prophylactic human papillomavirus (HPV) vaccination in developed countries. 1,2 An estimated 14,480 patients will be diagnosed and an estimated 4,290 females will die from cervical cancer in the United States in 2021. 3 Persistent HPV infection, especially high-risk HPV, is considered the principal cause of this disease.…”

Section: Introductionmentioning

confidence: 99%

Discovery of key genes as novel biomarkers specifically associated with HPV-negative cervical cancer

Liu

Jiang

et al. 2021

Molecular Therapy - Methods & Clinical Development

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Cervical cancer is a common female malignancy that is mainly caused by human papillomavirus (HPV) infection. However, the incidence of HPV-negative cervical cancer has shown an increasing trend in recent years. Because the mechanism of HPV-negative cervical cancer development is unclear, this study aims to find the pattern of differential gene expression in HPV-negative cervical cancer and verify the underlying potential mechanism. Differentially expressed genes were compared among HPV-positive cervical cancer, HPV-negative cervical cancer, and normal cervical tissues retrieved from TCGA. Subsequently, dysregulated differentially expressed genes specifically existed in HPV-negative cervical cancer tissues and HPV-negative cell lines were validated by qRT-PCR, western blotting, and immunohistochemical staining. We found seventeen highly expressed genes that were particularly associated with HPV-negative cervical cancer from analysis of TCGA database. Among the 17 novel genes, 7 genes (preferentially expressed antigen in melanoma [PRAME], HMGA2, ETS variant 4 [ETV4], MEX3A, TM7SF2, SLC19A1, and tweety-homologs 3 [TTYH3]) displayed significantly elevated expression in HPV-negative cervical cancer cells and HPV-negative cervical cancer tissues. Additionally, higher expression of MEX3A and TTYH3 was associated with a shorter overall survival of patients with HPV-negative cervical cancer. Our study implies that these seven genes are more likely to provide novel insights into the occurrence and progression of HPV-negative cervical cancer.

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“…2 The high mortality of cervical cancer is mainly due to the lack of early diagnosis, as the patients with advanced cervical cancer miss the opportunity for surgeries and are often resistant to radio/chemotherapy. [3][4][5] Great efforts have been invested to uncover the pathophysiology of cervical cancer, however, the exact underlying mechanisms are still elusive, which requires further exploration.…”

Section: Introductionmentioning

confidence: 99%

Identification of Hub Genes as Potential Prognostic Biomarkers in Cervical Cancer Using Comprehensive Bioinformatics Analysis and Validation Studies

Han

Sun

et al. 2021

CMAR

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Background: Cervical cancer belongs to one of the most common female cancers; yet, the exact underlying mechanisms are still elusive. Recently, microarray and sequencing technologies have been widely used for screening biomarkers and molecular mechanism discovery in cancer studies. In this study, we aimed to analyse the microarray datasets using comprehensive bioinformatics tools and identified novel biomarkers associated with the prognosis of patients with cervical cancer. Methods: The differentially expressed genes (DEGs) from Gene Expression Omnibus (GEO) datasets including GSE138080, GSE113942 and GSE63514 were analysed using GEO2R tool. The functional enrichment analysis was performed using g:Profiler tool. The protein-protein interaction (PPI) network construction and hub genes identification were performed using the STRING database and Cytoscape software, respectively. The hub genes were subjected to expression and survival analysis in the cervical cancer. The EdU incorporation and Cell Counting Kit-8 assays were performed to evaluate the effects of hub gene knockdown on the proliferation of cervical cancer cells. Results: A total of 89 overlapping DEGs (63 up-regulated and 26 down-regulated genes) were identified in the microarray datasets. The functional enrichment analysis indicated that the overlapping DEGs were mainly associated with "DNA replication" and "cell cycle". Furthermore, the PPI network analysis revealed that the network contains 87 nodes and 309 edges. Sub-module analysis using the Molecular Complex Detection tool identified 21 hub genes from the PPI network. The expression levels of the 21 hub genes were all up-regulated in the cervical cancer tissues when compared to normal cervical tissues as analysed by GEPIA tool. The survival analysis showed that the low expression of cell division cycle 45 (CDC45), GINS complex subunit 2 (GINS2), minichromosome maintenance complex component 2 (MCM2) and proliferating cell nuclear antigen (PCNA) was significantly correlated with the shorter overall survival of patients with cervical cancer. Moreover, the protein expression levels of GINS2, MCM2 and PCNA, but not CDC45, were significantly upregulated in the cervical cancer tissues when compared to normal cervical tissues. Finally, knockdown of MCM2 significantly suppressed the proliferation of HeLa and SiHa cells. Conclusion:In conclusion, we screened a total of 89 overlapping DEGs from the GEO datasets, and further analysis identified four hub genes (CDC45, GINS2, MCM2 and PCNA) that were likely associated with the prognosis of patients with cervical cancer. MCM2 knockdown repressed the cervical cancer cell proliferation. The current findings may provide novel insights into understanding the pathophysiology of cervical cancer and develop therapeutic targets for patients with cervical cancer.

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The role and contribution of treatment and imaging modalities in global cervical cancer management: survival estimates from a simulation-based analysis

Cited by 37 publications

References 25 publications

ZBTB28 induces autophagy by regulation of FIP200 and Bcl-XL facilitating cervical cancer cell apoptosis

ZBTB28 induces autophagy by regulation of FIP200 and Bcl-XL facilitating cervical cancer cell apoptosis

Discovery of key genes as novel biomarkers specifically associated with HPV-negative cervical cancer

Identification of Hub Genes as Potential Prognostic Biomarkers in Cervical Cancer Using Comprehensive Bioinformatics Analysis and Validation Studies

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