Understanding Cervical Cancer through Proteomics

Abstract

Cancer is one of the leading public health issues worldwide, and the number of cancer patients increases every day. Particularly, cervical cancer (CC) is still the second leading cause of cancer death in women from developing countries. Thus, it is essential to deepen our knowledge about the molecular pathogenesis of CC and propose new therapeutic targets and new methods to diagnose this disease in its early stages. Differential expression analysis using high-throughput techniques applied to biological samples allows determining the physiological state of normal cells and the changes produced by cancer development. The cluster of differential molecular profiles in the genome, the transcriptome, or the proteome is analyzed in the disease, and it is called the molecular signature of cancer. Proteomic analysis of biological samples of patients with different grades of cervical intraepithelial neoplasia (CIN) and CC has served to elucidate the pathways involved in the development and progression of cancer and identify cervical proteins associated with CC. However, several cervical carcinogenesis mechanisms are still unclear. Detecting pathologies in their earliest stages can significantly improve a patient's survival rate, prognosis, and recurrence. The present review is an update on the proteomic study of CC.

Keywords: biomarkers; cervical cancer; gene differential expression; proteomic.

Figure 1

General diagram of the workflow in proteomic studies in cervical cancer. Proteomic studies in cervical cancer are designed to search for biomarkers that could be used in the diagnosis, prognosis, and identification of new therapeutic targets, and they are carried out Figure 1. (1) Collection of biological samples from patients and controls such as: urine, vaginal cervical fluid, blood, and tumor tissue. If the samples start from cells, it is essential to perform cell lysis or mechanical destruction (freeze thaw, French press, sonication macerated with liquid N₂, lysis with detergents). (2) Purification of total proteins by centrifugation. The storage of the sample until its use at temperatures of −20 °C or −70 °C with or without protease inhibitor according to the chosen step of proteomic analysis to avoid any interference with the selected method. (3) Proteomic strategy selection, based on advanced techniques: protein microarray, mass spectrometry, Edman sequencing, 2D gel, 2D-DIGE. Quantitative techniques: ICAT, SILAC, iTRAQ. High throughput techniques: X-ray crystallography, NMR spectroscopy. (4) Match in databases and validation of candidates by ELISA, Western Blot or Immunohistochemistry. (5) Graphics construction. Partially created with BioRender.com.