Dados do Trabalho

Título

UPDATE ON MOLECULAR MARKERS FOR CERVICAL CANCER: A SYSTEMATIC REVIEW

Introdução

Cervical cancer is a major public health problem, being the third most frequent and the fourth leading cause of death in the female population in Brazil. Its incidence depends on risk factors and adherence to screening programs. Due to the growing prevalence in recent years, It’s necessary to identify which genetic and molecular markers can be used to improve outcomes and reduce mortality.

Objetivo

To identify molecular markers associated with prognosis or possible therapeutic targets.

Casuística

Women with cervical cancer

Método

This review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We searched in the PubMed/MEDLINE database from January 2012 to August 2022 for Clinical Trials, Meta-Analysis and Randomized Controlled Trial that met our inclusion criteria.

Resultados

Accordingly, we identified 13 articles. The analysis of the studies reveals that the expression of HER3, HIF-1α, HMGB1 and ERCC1 are associated with a bad prognosis and shorter survival. In addition, the TBLR1 protein, a marker of poor prognosis in cervical cancer, was pointed out as an important predictor of tumor invasion and metastasis. A cohort study showed that patients with ß-tubulin III expression had reduced responses to chemotherapy when compared to patients with less or no expression of it. In another study, it was observed that there is a risk of distant and lymph node metastasis with high expression of MTDH, describing it as a predictor of tumor deterioration. In contrast, the markers p16/Ki-67 have not been recommended for screening women with atypical cytology and low-grade squamous intraepithelial lesions due to insufficient high-quality evidence; however, there are studies that indicate p16 as a predictive of good prognosis in patients with cervical cancer. In addition to this, p53 and E-cadherin were related to LRIG3 expression in cervical cells, as was the use of progestogenic contraceptives. Further findings suggest that TP63 and MYC overexpression and the rate of HPV integration were correlated with progression from high-grade lesion to cervical cancer.

Conclusões

It is understood the need for knowledge and clinical-pathological applicability of the various biomarkers with a focus on optimizing prognosis and treatment.

Referências

1.HOU, Yongbin et al. Association of MTDH immunohistochemical expression with metastasis and prognosis in female reproduction malignancies: a systematic review and meta-analysis. Sci Rep, 2016. DOI 10.1038/srep38365. Disponível em: https://pubmed.ncbi.nlm.nih.gov/27917902/>.
2.HUANG, K et al. P16 expression in patients with cervical cancer and its prognostic significance: meta-analysis of published literature. Eur J Obstet Gynecol Reprod Biol, 2014. DOI 10.1016/j.ejogrb.2014.10.016. Disponível em: https://pubmed.ncbi.nlm.nih.gov/25461355/>.
3.HUANG, Miaoling et al. Overexpression of hypoxia-inducible factor-1α is a predictor of poor prognosis in cervical cancer: a clinicopathologic study and a meta-analysis. Int J Gynecol Cancer, 2014. DOI 10.1097/IGC.0000000000000162. Disponível em: https://pubmed.ncbi.nlm.nih.gov/24978711/>.
4.KARAGEORGOPOULOU, Sofia et al. Prognostic and predictive factors in patients with metastatic or recurrent cervical cancer treated with platinum-based chemotherapy. BMC Cancer, 2017. DOI 10.1186/s12885-017-3435-x. Disponível em: https://pubmed.ncbi.nlm.nih.gov/28659181/>.
5. KISSER, A et al. A systematic review of p16/Ki-67 immuno-testing for triage of low grade cervical cytology. BJOG, 2015. DOI 10.1111/1471-0528.13076. Disponível em: https://pubmed.ncbi.nlm.nih.gov/25208923/>.
6. LI, Weiwei et al. Serum human kallikrein 7 represents a new marker for cervical cancer. Med Oncol, 2014. DOI 10.1007/s12032-014-0208-0. Disponível em: https://pubmed.ncbi.nlm.nih.gov/25182706/>.
7.LINDSTRÖM, A K et al. Immunohistochemical LRIG3 expression in cervical intraepithelial neoplasia and invasive squamous cell cervical cancer: association with expression of tumor markers, hormones, high-risk HPV-infection, smoking and patient outcome. Eur J Histochem , 2014. DOI 10.4081/ejh.2014.2227. Disponível em: https://pubmed.ncbi.nlm.nih.gov/24998916/>.
8. NGO, Charlotte et al. From prospective biobanking to precision medicine: BIO-RAIDs - an EU study protocol in cervical cancer. BMC Cancer, 2015. DOI 10.1186/s12885-015-1801-0. Disponível em: https://pubmed.ncbi.nlm.nih.gov/26531748/>.
9.OCANA, Alberto et al. HER3 overexpression and survival in solid tumors: a meta-analysis. J Natl Cancer Inst, 2013. DOI 10.1093/jnci/djs501. Disponível em: https://pubmed.ncbi.nlm.nih.gov/23221996/>.
10.SILVA, Daliana Caldas et al. Immunohistochemical expression of p16, Ki-67 and p53 in cervical lesions - A systematic review. Pathol Res Pract, 2017. DOI 10.1016/j.prp.2017.03.003. Disponível em: https://pubmed.ncbi.nlm.nih.gov/28554769/>.
11.WANG, J et al. TBLR1 is a novel prognostic marker and promotes epithelial-mesenchymal transition in cervical cancer. Br J Cancer, 2014. DOI 10.1038/bjc.2014.278. Disponível em: https://pubmed.ncbi.nlm.nih.gov/24874481/>.
12.WU, Tengyun et al. HMGB1 overexpression as a prognostic factor for survival in cancer: a meta-analysis and systematic review. Oncotarget, 2016. DOI 10.18632/oncotarget.10413. Disponível em: https://pubmed.ncbi.nlm.nih.gov/27391431/>.
13.ZHU, Da et al. Amplification and overexpression of TP63 and MYC as biomarkers for transition of cervical intraepithelial neoplasia to cervical cancer. Int J Gynecol Cancer, 2014. DOI 10.1097/IGC.0000000000000122.Disponível em: https://pubmed.ncbi.nlm.nih.gov/24662128/>.

Palavras Chave

Molecular markers; Cervical cancer; Prognosis