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Gene & Protein in Disease

ORIGINAL RESEARCH ARTICLE
Pre-metastatic niche in oral squamous cell

carcinoma: Insights from a transcriptomic
meta-analysis

Ana Kelly Fernandes Duarte 1† , Heloisa de Almeida Freitas 1† ,
Genilda Castro de Omena Neta 2 , Rodger Marcel Lima Rocha 1 ,
Thaysa Kelly Barbosa Vieira 2 , Karol Fireman de Farias 2 ,
Bruna Del Vechio Koike 3 , Carolinne de Sales Marques 4 , and
Carlos Alberto de Carvalho Fraga²*

1 Institute of Pharmaceutical Sciences, Federal University of the Alagoas, Maceió, Alagoas, Brazil
2 Medical and Nursing Science Complex, Federal University of the Alagoas, Arapiraca, Alagoas,
Brazil
3 Medical College, Federal University of the San Francisco Valley, Petrolina, Pernambuco, Brazil
4 Department of Genetics, Institute of Biological and Health Sciences, Federal University of the
Alagoas, Maceió, Alagoas, Brazil

Abstract

Primary tumors can precondition a pre-metastatic niche, promoting the colonization
of circulating neoplastic cells and influencing the secondary tumor microenvironment.
Nevertheless, the mechanisms underlying the formation of this niche, as well as perineural
† These authors contributed equally invasion in oral squamous cell carcinoma (OSCC), are not well-elucidated. The study aims
to this work.
to identify differentially expressed genes (DEGs) and related pathways associated with
*Corresponding author: pre-metastatic niche and perineural invasion in OSCC. We evaluated metastatic and
Carlos Alberto de Carvalho Fraga
(carlos.fraga@arapiraca.ufal.br) non-metastatic primary tumor samples, healthy oral tissues, OSCC samples, metastatic
lymph nodes from patients with OSCC, and normal lymph node samples. The GEO2R
Citation: Duarte AKF, Freitas HA, tool was applied to identify mRNAs differentially expressed between tissues exhibiting
Neta GCO, et al. Pre-metastatic
niche in oral squamous cell features of a pre-metastatic niche and normal tissue samples, including selected non-
carcinoma: Insights from a metastatic and metastatic OSCC samples. We also performed an analysis of perineural
transcriptomic meta-analysis. Gene invasion-negative and perineural invasion-positive tumor samples. Our data revealed
Protein Dis. 2024;3(4):2971.
doi: 10.36922/gpd.2971 that SERPINE1, SPP1, CALCA, and MMP13 genes were upregulated. These upregulated
genes are associated with several cancer-related pathways, while downregulated genes
Received: February 19, 2024
Accepted: July 16, 2024 are mainly associated with immune responses, axon guidance, and the neurotrophin
Published Online: November 20, signaling pathway. Given the upregulation of the circadian rhythm pathway in
2024 metastatic lymph nodes, we also performed a correlation analysis that allows users to
Copyright: © 2024 Author(s). compute function-specific parameters, with resulting figures dynamically displayed
This is an Open-Access article to conveniently access the tumor’s immunological, clinical, and genomic features.
distributed under the terms of the
Creative Commons Attribution Downregulation of the circadian rhythm gene PER3 and upregulation of Bhlhe40
License, permitting distribution, were associated with poor survival outcomes. In conclusion, we postulate that during
and reproduction in any medium, lymph node invasion, OSCCs activate axonal guidance genes, such as SERPENE1, L1AM,
provided the original work is
properly cited. CXCR4, and SPP1. As neoplastic cells establish themselves, circadian rhythm genes are
upregulated, contributing to immune evasion and promoting tumor growth.
Publisher’s Note: AccScience
Publishing remains neutral with
regard to jurisdictional claims in Keywords: Metastasis; Circadian rhythm; Oral cancer; Cancer microenvironment
published maps and institutional
affiliations.

Volume 3 Issue 4 (2024) 1 doi: 10.36922/gpd.2971