Potential Markers from Serum-Purified Exosomes for Detecting Oral Squamous Cell Carcinoma Metastasis

Abstract

Background: Blood contains exosomes that are related to tumor cells. Those exosomes can regulate communication between cells and have a great influence on a variety of tumor-associated proceedings through their target cells. Therefore, serum exosomes (SE) were supposed to play a crucial role in cancer development.Methods: This study presented a quantitative proteomics analysis to identify the protein content in SEs including 30 subjects from oral squamous cell carcinoma (OSCC) patients with lymph node metastasis (LNM), OSCC patients with no LNM (NLNM), and healthy controls (HC). Differentially expressed proteins (DEP) were analyzed by bioinformatics, and then a total of 30 subjects were used for Western blot and 60 subjects for IHC, ELISA, and RT-PCR verifications. The correlations were assessed between DEP expression and clinicopathologic factors.Results: A total of 415 proteins were identified. Comparing with HC and OSCC-NLNM, we found 37 proteins and 28 proteins in the SEs of OSCC-LNM, respectively. There were significant correlations among the expression of PF4V1 with tumor differentiation level, PF4V1 and F13A1 with the number of positive nodes, and ApoA1 with smoking and drinking. ROC curve analysis indicated that the combinations of the different biomarkers or specimen were obviously superior to single biomarker or specimen for diagnosing OSCC-LNM.Conclusions: We conclude that PF4V1, CXCL7, F13A1, and ApoA1 from SEs may be related to the metastasis of OSCC, which would be helpful in the diagnosis of OSCC-LNM.Impact: Biomarkers from SEs could help with the diagnosis of metastasis in OSCC.

Exosomal cargoes in OSCC: current findings and potential functions

“…Observing that OSCC LN1-1 cells were more aggressive in lymphatic node metastasis than OEC-M1 cells, Wang et al (2019a) used stable isotope amino acid labeling to reveal that higher laminin-332 protein levels in tumor cell-derived exosomes was a major cause for the superior lymphangiogenesis ability of OSCC LN1-1 cells, as laminin-332 promotes lymphatic endothelial cell migration and tube formation. Li et al (2019a) reported that PF4V1, CXCL7, F13A1, and ApoA1 could affect OSCC lymph node metastasis, and the mechanism remains unknown.…”

PF4V1 affects the progression of oral squamous cell carcinoma by regulating Wnt/β-catenin pathway and angiogenesis

“…PF4V1 was evidenced to have statistically significant expressions in cancer tissue samples compared with para-carcinoma tissue samples [21,22]. Additionally, our previous research also found that PF4V1 was not expressed or at a low level in the test samples from OSCC patients with lymph node metastasis compared with OSCC patients with no lymph node metastasis and the healthy population [18]. A close relationship existed between PF4V1 and OSCC.…”

“…More and more researches have revealed that PF4V1 regulated cell differentiation, proliferation, and apoptosis [7,16,17]. Our previous study showed that PF4V1 had a close relationship with OSCC [18]. Nevertheless, there has been no study that reports the relationship between PF4V1 and Wnt/β-catenin and EMT pathways in OSCC.…”

Extracellular Vesicles in Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders: A Systematic Review

“…Serum exosomal protein content has been measured and explored as an indicator of locoregional spread. [54] isolated exosomes from serum of subjects, 10 each with OSCC with lymph node metastasis (LNM), OSCC with no LNM (NLNM) and healthy controls (HC). Proteomic comparison using a combination of liquid chromatography-mass spectrometry and mass spectrometry followed by clustering into gene ontology categories.…”

“…Of 415 proteins identified, 37 and 28 differentially expressed proteins were identified in OSCC-LNM compared to HC and OSCC-NLNM, respectively. Combined with qPCR-based validation findings from tissue, serum and whole blood samples, they highlighted that serum exosomal proteins, PF4V1, CXCL7, F13A1 and ApoA1 may be related to the OSCC lymph node metastasis [54]. ROC analysis using relative abundances of ApoA1, CXCL7, PF4V1 and F13A1 in serum, serum exosomes and whole blood indicated some potential application as novel predictive circulating biomarkers for OSCC with LNM but are not useful in prognosis.…”