SPOCK1 overexpression suggests poor prognosis in head and neck squamous cell carcinomas.

Head and neck squamous cell carcinomas (HNSCCs) are mostly associated with smoking, alcohol intake, and/or human papillomavirus HPV16 and/or HPV18 infection. However, most tumors are diagnosed at an advanced stage. In the search for biomarkers of HNSCC, we studied the prognostic role of SPOCK1, a heparan sulfate proteoglycan. In HNSCC, SPOCK1 expression was tested both at in silico mRNA level using the Kaplan-Meier Plotter and at in situ protein level after SPOCK1 immunohistochemistry after whole slide digitalization. Protein expression results were analyzed using H-Scores, both by eye-control testing and with a machine-learning-based automated image analysis tool, DensitoQuant. SPOCK1 mRNA expression was found to be significantly higher in oral carcinomas than in the normal oral mucosa (log-rank p = 5.76e-06). Elevated SPOCK1 mRNA expression was consistently associated with a strongly reduced overall survival (OS; HR = 1.57 (1.2-2.06); log-rank p = 0.001) in HNSCC. This was particularly true for tumors with high (log-rank p = 0.00085) vs. low (log-rank p = 0.55) neoantigen (NeoAG) levels, at median antigen level stratification. Both the Cox-regression analysis and the log-rank test revealed elevated SPOCK1 protein levels in association with significantly reduced OS in our 97 HNSCC patients (both p = 0.002), which was supported by automated image analysis testing (p = 0.008 and p = 0.044, respectively). Our findings suggest that SPOCK1 can be a candidate adverse prognostic biomarker also in HNSCC. Therefore, SPOCK1 overexpression may specify a group of oral cancers with aggressive tumor biology.