# Five Cellular Genes as Candidates for Cervical Adenocarcinoma Molecular Markers

**Authors:** Isui Abril García-Montoya, Karla Berenice López-Córdova, Daniel Marrero-Rodríguez, Mauricio Salcedo-Vargas, Claudia Lucía Vargas-Requena, Angélica Maria Escárcega-Avila, Santos Adriana Martel-Estrada, Florinda Jiménez-Vega

PMC · DOI: 10.3390/cancers17091558 · 2025-05-03

## TL;DR

This study identifies five genes that could serve as molecular markers for cervical adenocarcinoma, a type of cervical cancer linked to HPV infection.

## Contribution

The study proposes a novel five-gene panel as potential molecular markers for HPV-associated cervical adenocarcinoma.

## Key findings

- Five genes (RARβ, MACC1, BCL2, HOXC8, and E6/E7/HPV) showed higher statistical significance in cervical adenocarcinoma samples.
- These genes could serve as a molecular tool for detecting HPV-associated cervical adenocarcinoma.
- Bioinformatic analysis and RT-PCR validation identified differentially expressed genes in cervical cancer.

## Abstract

This study describes the search for and evaluation of cervical adenocarcinoma molecular markers in a population of Ciudad Juárez, Chihuahua, México. Bioinformatic analysis of the NCBI database and 161 transcriptomic libraries was performed. The expression of selected genes was analyzed using semi-quantitative RT-PCR in samples from fresh cervical adenocarcinoma and cervical normal tissues. Five genes presented higher amplification frequency with a statistically significant difference, making them possible molecular markers for cervical cancer.

Background/Aim: Cervical adenocarcinoma associated with Human Papillomavirus (HPV) infection represents 85–90% of all adenocarcinomas that have poor prognostic factors and is an important health public concern. Currently, cervical adenocarcinoma molecular markers are scarce. This study searched databases and the literature regarding candidate genes to find these molecular markers, which were experimentally evaluated in fresh cervical samples. Materials and Methods: Bioinformatic analysis of 161 transcriptomic libraries of cervical tissues with or without lesions from the NCBI database was performed using the Partek Genomics Suite 6.6v software. The selected genes with a p value of >0.05, and 1.5-fold change were considered. A search of molecular marker candidates of cervical lesions that were already published in the literature was performed. To validate the selected genes, total RNA from fresh cervical adenocarcinoma and cervical normal tissues were subjected to RT-PCR experiments; HPV detection was also performed. Results: Initially, twenty-five genes were identified using bioinformatic analysis, and their expression was evaluated. The results showed that the HOXC6, HOXC8, RARβ, ELAVL2, URG4, CISD2, CA9, BCL2, Survivin, MACC1, CDKN2A, and HPV E6/E7 genes were found to be differentially expressed in CC. Among these, RARβ, MACC1, BCL2, HOXC8, and E6/E7/HPV exhibited higher statistical significance for CC samples. Conclusions: This five-gene panel could serve as a novel molecular tool for HPV-associated cervical adenocarcinoma detection.

## Linked entities

- **Genes:** HOXC6 (homeobox C6) [NCBI Gene 3223], HOXC8 (homeobox C8) [NCBI Gene 3224], RARB (retinoic acid receptor beta) [NCBI Gene 5915], ELAVL2 (ELAV like RNA binding protein 2) [NCBI Gene 1993], URGCP (upregulator of cell proliferation) [NCBI Gene 55665], CISD2 (CDGSH iron sulfur domain 2) [NCBI Gene 493856], CA9 (carbonic anhydrase 9) [NCBI Gene 768], BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596], birc5a (baculoviral IAP repeat containing 5a) [NCBI Gene 373110], MACC1 (MET transcriptional regulator MACC1) [NCBI Gene 346389], CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029]
- **Diseases:** cervical adenocarcinoma (MONDO:0005153)

## Full-text entities

- **Genes:** MACC1 (MET transcriptional regulator MACC1) [NCBI Gene 346389] {aka 7A5, SH3BP4L}, RARB (retinoic acid receptor beta) [NCBI Gene 5915] {aka HAP, MCOPS12, NR1B2, RARbeta, RARbeta1, RRB2}, URGCP (upregulator of cell proliferation) [NCBI Gene 55665] {aka URG4}, ELAVL2 (ELAV like RNA binding protein 2) [NCBI Gene 1993] {aka HEL-N1, HELN1, HUB}, CA9 (carbonic anhydrase 9) [NCBI Gene 768] {aka CAIX, MN}, CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029] {aka ARF, CAI2, CDK4I, CDKN2, CMM2, INK4}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, HOXC6 (homeobox C6) [NCBI Gene 3223] {aka CP25, HHO.C8, HOX3, HOX3C}, CISD2 (CDGSH iron sulfur domain 2) [NCBI Gene 493856] {aka ERIS, Miner1, NAF-1, WFS2, ZCD2}, HOXC8 (homeobox C8) [NCBI Gene 3224] {aka HOX3, HOX3A}
- **Diseases:** cervical lesions (MESH:D002575), Cervical Adenocarcinoma (MESH:D000230)
- **Species:** Human papillomavirus (species) [taxon 10566]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12071559/full.md

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Source: https://tomesphere.com/paper/PMC12071559