Validation of Selected Head and Neck Cancer Prognostic Markers from the Pathology Atlas in an Oral Tongue Cancer Cohort

Abstract

The Pathology Atlas is an open-access database that reports the prognostic value of protein-coding transcripts in 17 cancers, including head and neck cancer. However, cancers of the various head and neck anatomical sites are specific biological entities. Thus, the aim of the present study was to validate promising prognostic markers for head and neck cancer reported in the Pathology Atlas in oral tongue squamous cell carcinoma (OTSCC). We selected three promising markers from the Pathology Atlas (CALML5, CD59, LIMA1), and analyzed their prognostic value in a Norwegian OTSCC cohort comprising 121 patients. We correlated target protein and mRNA expression in formalin-fixed, paraffin-embedded cancer tissue to five-year disease-specific survival (DSS) in univariate and multivariate analyses. Protein expression of CALML5 and LIMA1 were significantly associated with five-year DSS in the OTSCC cohort in univariate analyses (p = 0.016 and p = 0.043, respectively). In multivariate analyses, lymph node metastases, tumor differentiation, and CALML5 were independent prognosticators. The prognostic role of the other selected markers for head and neck cancer patients identified through unbiased approaches could not be validated in our OTSCC cohort. This underlines the need for subsite-specific analyses for head and neck cancer.

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“…CALML5, known as calmodulin-like 5, is a skin-specific calcium-binding protein that is closely related to keratinocyte differentiation (Mehul 11 et al, 2001). A previous study showed that the high expression of CALML5 was strongly associated with better survival in patients with head and neck squamous cell carcinomas (Wirsing et al, 2021). Misawa et al (Misawa et al, 2020) reported that the methylation of CALML5, led to its downregulation, and this showed a correlation with HPV-associated oropharyngeal cancer.…”

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“…CALML5, known as calmodulin-like 5, is a skin-specific calcium-binding protein that is closely related to keratinocyte differentiation ( Mehul et al, 2001 ). A previous study showed that the high expression of CALML5 was strongly associated with better survival in patients with head and neck squamous cell carcinomas ( Wirsing et al, 2021 ). Misawa et al ( Misawa et al, 2020 ) reported that the methylation of CALML5, led to its downregulation, and this showed a correlation with HPV-associated oropharyngeal cancer.…”

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“…CALML5 and FCGBP are on the list of favorable prognostic genes for HNSCC (available at ; , respectively). Furthermore, CALML5 was validated by the HNSCC cohort at mRNA and protein levels [ 44 , 52 ].…”

“…CALML5 expression could be a protective mechanism for patient survival. Furthermore, CALML5 was validated by the HNSCC cohort at mRNA and protein levels [ 44 , 52 ].…”

“…CALML5 and FCGBP are on the list of favorable prognostic genes for HNSCC (available at https://www.protei natlas.org/ENSG00000178372-CALML5/pathology; https://www.proteinatlas.org/ENS G00000275395-FCGBP/pathology, respectively). Furthermore, CALML5 was validated by the HNSCC cohort at mRNA and protein levels [44,52].…”