Abstract

Lymph node metastasis (LNM) is an important prognostic factor in cervical cancer (CC). In early stages, the risk of LNM is approximately 3.7 to 21.7%, and the 5-year overall survival decreases from 80% to 53% when metastatic disease is identified in the lymph nodes. Few reports have analyzed the relationship between miRNA expression and the presence of LNM. The aim of this study was to identify a subset of miRNAs related to LNM in early-stage CC patients. Formalin-fixed paraffin-embedded tissue blocks were collected from patients with early-stage CC treated by radical hysterectomy with lymphadenectomy. We analyzed samples from two groups of patients—one group with LNM and the other without LNM. Global miRNA expression was identified by microarray analysis, and cluster analysis was used to determine a subset of miRNAs associated with LNM. Microarray expression profiling identified a subset of 36 differentially expressed miRNAs in the two groups (fold change (FC) ≥ 1.5 and p < 0.01). We validated the expression of seven miRNAs; miR-487b, miR-29b-2-5p, and miR-195 were underexpressed, and miR-92b-5p, miR-483-5p, miR-4534, and miR-548ac were overexpressed according to the microarray experiments. This signature exhibited prognostic value for identifying early-stage CC patients with LNM. These findings may help detect LNM that cannot be observed in imaging studies.

Highlights

  • Licensee MDPI, Basel, Switzerland.Cervical carcinoma (CC) is one of the most common cancers in women from lowincome and middle-income countries; in Mexico, CC is the second most common tumor and has a high mortality rate [1]

  • Formalin-fixed paraffin-embedded (FFPE) tissue blocks from early-stage CC patients treated with radical hysterectomy (RH) and bilateral pelvic lymphadenectomy (BPL) who were diagnosed between January 2006 and December 2013 at the Instituto Nacional de Cancerología (Mexico City) were reviewed

  • Patients, and 13 samples were selected from lymph node metastasis (LNM)− patients

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Summary

Introduction

Licensee MDPI, Basel, Switzerland.Cervical carcinoma (CC) is one of the most common cancers in women from lowincome and middle-income countries; in Mexico, CC is the second most common tumor and has a high mortality rate [1]. The most important factors affecting survival of patients with early-stage CC (International Federation of Gynecology and Obstetrics (FIGO) stage. The risk of LNM is approximately 3.7 to 21.7%, and the 5-year overall survival (OS) decreases from 80% to 53% when metastatic disease is identified in the lymph nodes (LNM+) [3,4,5,6]. The FIGO updated their staging system in 2018 by incorporating nodal status into stage III disease. The standard technique to identify positive lymph nodes is based on advanced imaging methods such magnetic resonance imaging (MRI), computed tomography (CT), or positron emission tomography–CT (PET)–CT. The accuracy of each of these modalities ranges from 70 to 85%, and the lymph nodes must reach a minimum size to be identified by imaging studies. Microscopic disease cannot be detected by noninvasive methods [7,8,9,10]

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