{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:51:10Z","timestamp":1788223870240,"version":"build-2803163510"},"reference-count":47,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Atrium Health Foundation Research fund and Comprehensive Cancer Institute","award":["55811085045814"],"award-info":[{"award-number":["55811085045814"]}]},{"name":"Atrium Health Foundation Research fund and Comprehensive Cancer Institute","award":["P30CA012197-39"],"award-info":[{"award-number":["P30CA012197-39"]}]},{"name":"Wake Forest Baptist Comprehensive Cancer Center\u2019s NCI Cancer Center","award":["55811085045814"],"award-info":[{"award-number":["55811085045814"]}]},{"name":"Wake Forest Baptist Comprehensive Cancer Center\u2019s NCI Cancer Center","award":["P30CA012197-39"],"award-info":[{"award-number":["P30CA012197-39"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Oral squamous cell carcinoma (OSCC) is a malignancy that affects the oral mucosa and is characterized by indurated oral lesions. The RNAseq of formalin-fixed, paraffin-embedded (FFPE) samples is readily available in clinical settings. Such samples have long-term preservation and can provide highly accurate transcriptomic information regarding gene fusions, isoforms, and allele-specific expression. We determined differentially expressed genes using the transcriptomic profiles of oral potentially malignant disorder (OPMD) FFPE oral lesion samples of patients who developed OSCC over years. A technical comparison was completed comparing breast cancer (BC) FFPE publicly available data in this proof-of-concept pilot study. OSCC FFPE samples were collected from patients (N = 3) who developed OSCC 3 to 5 years following OPMD diagnosis (n = 3) and were analyzed using RNAseq. RNAseq sequences from the FFPE OSCC samples and publicly available FFPE samples of BC patients (n = 6) (Gene Expression Omnibus Database, GSE58135) aligned to human reference (GRCh38.p13). Genes were counted using the Spliced Transcripts Alignment to a Reference (STARv2.7.9a) software. Differential expression was determined in R using DESeq2v1.40.2 comparing OSCC to BC samples. Principal component analysis (PCA) plots were completed. Differential Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were determined via the Pathviewv.1.40.0 program. STRING v12.0 was used to determine protein\u2013protein interactions between genes represented in more than one KEGG pathway. STARv2.7.9a identified 27,237 and 30,343 genes among the OSCC and BC groups, respectively. DESeq2v1.40.2 determined 9194 differentially expressed genes (DEPs), 4466 being upregulated (OSCC &gt; BC) and 4728 being downregulated (BC &gt; OSCC) (padj &lt; 0.05). Most significant genes included KRT6B, SERPINB5, and DSC3 (5- to 10-fold change range; padj &lt; 10 \u00d7 10\u2212100). PCA showed that BC and OSCC samples clustered as separate groups. Pathviewv.1.40.0 identified 17 downregulated KEGG pathways in OSCC compared to the BC group. No upregulated KEGG pathways were identified. STRINGv12.0 determined Gene Ontology Biological Process enrichments for leukocytes and apoptosis in upregulated KEGG genes including multiple PIK3 genes and NIK\/NF-kappaB signaling and metabolic responses from lipopolysaccharides in downregulated KEGG genes including CHUK and NFKB1. Using FFPE samples, we determined DEPs characteristic of OSCC and distinct from BC. KRT-family genes and lipopolysaccharide producing periodontal pathogens may be further investigated for their involvement in the OPMD to OSCC transition.<\/jats:p>","DOI":"10.3390\/ijms26136263","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T05:28:28Z","timestamp":1751347708000},"page":"6263","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Transcriptomic Profile of Oral Cancer Lesions: A Proof-of-Concept Pilot Study of FFPE Tissue Sections"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1874-7742","authenticated-orcid":false,"given":"Madison E.","family":"Richards","sequence":"first","affiliation":[{"name":"Department of Oral Medicine\/Oral and Maxillofacial Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC 28203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micaela F.","family":"Beckman","sequence":"additional","affiliation":[{"name":"Translational Research Laboratories, Cannon Research Center & Oral Medicine, Atrium Health Carolinas Medical Center, Charlotte, NC 28203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"Martinez Duarte","sequence":"additional","affiliation":[{"name":"Carolinas Pathology Group, Atrium Health Carolinas Medical Center, Charlotte, NC 28203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel J.","family":"Napenas","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine\/Oral and Maxillofacial Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC 28203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Brennan","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine\/Oral and Maxillofacial Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC 28203, USA"},{"name":"Department of Otolaryngology\/Head and Neck Surgery, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8903-333X","authenticated-orcid":false,"given":"Farah","family":"Bahrani Mougeot","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine\/Oral and Maxillofacial Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC 28203, USA"},{"name":"Translational Research Laboratories, Cannon Research Center & Oral Medicine, Atrium Health Carolinas Medical Center, Charlotte, NC 28203, USA"},{"name":"Department of Otolaryngology\/Head and Neck Surgery, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8953-1769","authenticated-orcid":false,"given":"Jean-Luc C.","family":"Mougeot","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine\/Oral and Maxillofacial Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC 28203, USA"},{"name":"Translational Research Laboratories, Cannon Research Center & Oral Medicine, Atrium Health Carolinas Medical Center, Charlotte, NC 28203, USA"},{"name":"Department of Otolaryngology\/Head and Neck Surgery, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/0030-4220(78)90383-3","article-title":"Definition of leukoplakia and related lesions: An aid to studies on oral precancer","volume":"46","author":"Kramer","year":"1978","journal-title":"Oral Surg. 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