Molecular alterations in oral cancer using high-throughput proteomic analysis of formalin-fixed paraffin-embedded tissue

Abstract

Loss of cell differentiation is a hallmark for the progression of oral squamous cell carcinoma (OSCC). Archival Formalin-Fixed Paraffin-Embedded (FFPE) tissues constitute a valuable resource for studying the differentiation of OSCC and can offer valuable insights into the process of tumor progression. In the current study, we performed LC-MS/MS-based quantitative proteomics of FFPE specimens from pathologically-confirmed well-differentiated, moderately-differentiated, and poorly-differentiated OSCC cases. The data were analyzed in four technical replicates, resulting in the identification of 2376 proteins. Of these, 141 and 109 were differentially expressed in moderately-differentiated and poorly differentiated OSCC cases, respectively, compared to well-differentiated OSCC. The data revealed significant metabolic reprogramming with respect to lipid metabolism and glycolysis with proteins belonging to both these processes downregulated in moderatelydifferentiated OSCC when compared to well-differentiated OSCC. Signaling pathway analysis indicated the alteration of extracellular matrix organization, muscle contraction, and glucose metabolism pathways across tumor grades. The extracellular matrix organization pathway was upregulated in moderately-differentiated OSCC and downregulated in poorly differentiated OSCC, compared to well-differentiated OSCC. PADI4, an epigenetic enzyme transcriptional regulator, and its transcriptional target HIST1H1B were both found to be upregulated in moderately differentiated and poorly differentiated OSCC, indicating epigenetic events underlying tumor differentiation. In conclusion, the findings support the advantage of using high-resolution mass spectrometry-based FFPE archival blocks for clinical and translational research. The candidate signaling pathways identified in the study could be used to develop potential therapeutic targets for OSCC.

Identifying Biomarkers and Therapeutic Targets by Multiomic Analysis for HNSCC: Precision Medicine and Healthcare Management

“…In this context, suitable biomarkers for the accurate detection and diagnosis of HNSCC are very sought-after, and intensive efforts are ongoing. A recent study showed that lipid metabolism-related proteins, which are differentially expressed in OSCC with variable differentiation, can be used as prognostic biomarkers for OSCC . In this study, using very stringent criteria, we identified a list of genes that show higher differential expression in HNSCC using actual patient data samples that were profiled using a standard pipeline of gene expression studies at the mRNA and protein levels.…”

“…A recent study showed that lipid metabolism-related proteins, which are differentially expressed in OSCC with variable differentiation, can be used as prognostic biomarkers for OSCC. 34 In this study, using very stringent criteria, we identified a list of genes that show higher differential expression in HNSCC using actual patient data samples that were profiled using a standard pipeline of gene expression studies at the mRNA and protein levels. Although many genes show a higher expression in HNSCC, we narrowed this down to 60 candidate genes and tested their expression at the mRNA and protein levels.…”

Expression signature and molecular basis of CDH11 in OSCC detected by a combination of multiple methods

“…We also paid attention to genes co-expressed with CDH11 in OSCC and extended the analysis to the biological process, molecular functions, and pathways enriched by genes positively or negatively co-expressed with CDH11 in OSCC. The majority of the biological processes or pathways that were significantly clustered by co-expressed genes, including extracellular matrix organization, the epithelial to mesenchymal transition, carbon metabolism, and the PI3K-Akt signaling pathway, have been reported to be involved in the carcinogenesis of OSCC [ 26 – 39 ]. Thus, CDH11 might contribute to the occurrence and development of OSCC through co-work with co-expressed genes participating in these altered biological processes or pathways.…”

Emerging histological and serological biomarkers in oral squamous cell carcinoma: Applications in diagnosis, prognosis evaluation and personalized therapeutics (Review)

“…In recent years, several potential histological biomarkers of p16 INK4A have been identified and their functions in OSCC have been studied in detail. These include markers of cell cycle regulation (p16 INK4A , cyclin D1), EGFR, cell proliferation (Ki-67), immune checkpoint proteins [programmed cell death 1 (PD-1) ligand 1 (PD-L1)] and others involved in tissue invasion and metastasis, such as metalloproteinases ( 28 ).…”