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Novel diagnostic biomarkers in serum identify patients with OSCC

ABSTRACT: Purpose No blood biomarkers to detect early OSCC without clinical signs exist - diagnosis is solely based on histology of a visible tumor. Most OSCC patients are diagnosed at advanced stage, which leads to significant morbidity and poor survival. If high-risk patients were identified with blood-based biomarkers before clear clinical manifestations, tumors could be detected and treated at earlier stage. Patients and Methods Serum samples were collected from patients with OSCC at the Department of Otorhinolaryngology – Head and Neck Surgery, Helsinki University Hospital (Finland). Age and gender matched healthy individuals served as controls. Quantitative proteomic analysis with mass spectrometry was performed. Results We quantified 388 proteins in the serum samples. A complete separation between cases and controls was seen based on the protein expression profiles. With statistical analyses, we identified a set of eight proteins that most reliably separated OSCC patients from healthy individuals. Although the tumor stages varied from I to IVa, this set of proteins was able to identify all OSCCs and thus is sensitive for detecting even early tumors. Conclusion We are the first to suggest a set of serum biomarkers to be evaluated further as a diagnostic panel to detect preclinical OSCC in risk patients.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Serum

SUBMITTER: Sakari Joenväärä

LAB HEAD: Suvi Renkonen

PROVIDER: PXD005263 | Pride | 2018-04-25

REPOSITORIES: Pride

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Project description:The majority of meningiomas are benign tumors associated with favorable outcomes; however, the less common aggressive variants with unfavorable outcomes often recur and may be due to sub-populations of less-differentiated cells residing within the tumor. These sub-populations of tumor cells, termed tumor-initiating cells, may be isolated from heterogeneous tumors when sorted or cultured in defined medium designed for enrichment of the tumor-initiating cells. We report the isolation and characterization of a population of tumor-initiating cells derived from an atypical meningioma. These meningioma-initiating cells (MICs) self-renew, differentiate, and can recapitulate the histological characteristics of the parental tumor when transplanted into athymic nude mice. Immunohistochemistry reveals protein expression patterns similar to neural stem and progenitor cells while genomic profiling verified the isolation of cancer cells (with defined meningioma chromosomal aberrations) from the bulk tumor. Furthermore, microarray analysis of gene expression reveals that many epithelial to mesenchymal transition genes are upregulated in the MICs, consistent with the presence of both neural stem cell and mature neural cell molecular markers seen in the derived cultures. Pathway analysis identifies biochemical processes and gene networks related to aberrant cell cycle progression, particularly the loss of heterozygosity of tumor suppressor genes CDKN2A (p16INK4A), p14ARF, and CDKN2B (p15INK4B). Flow cytometric analysis revealed the expression of CD44 and activated leukocyte adhesion molecule (ALCAM/CD166); these may prove to be markers able to identify this cell type. In conclusion, we identify a tumor-initiating population from an atypical meningioma that displays a unique phenotype and these results provide increased understanding of atypical meningioma progression. Part 1 of 2: Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from primary tissue and their counterpart cell lines Part 2 of 2: Illumina gene expression array analysis was performed according to the manufacturer's directions on RNA extracted from cultured primary Meningioma and neural stem cell lines

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Novel diagnostic biomarkers in serum identify patients with OSCC

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