Altered Immune-Related Gene Expressions Indicate Oral Cancer Nodal Disease

Abstract

Lymph nodal disease (LN+) is the most significant prognostic factor of oral squamous cell carcinoma (OSCC). Current risk indicator(s) for guiding elective neck dissection (END) is insufficient for clinically node-negative (cN0) patients, resulting in under- or overtreatment. While the role of immunological events in tumorigenesis and metastasis is evident, the prognostic implication in OSCC remains unclear. The study objective was to investigate large-scale immune-related gene expression and determine its prognostic value on node-free survival (NFS). We analyzed patients who received intent-to-cure surgery with at least 3 y of follow-up and known outcome of LN through a pan-Canadian surgical trial. Total RNA was extracted from surgical tissues with >70% tumor content and analyzed on a 730-gene panel (NanoString nCounter® PanCancer Immune Panel). We first profiled gene expression in a fresh-frozen (FF) discovery set to identify differentially expressed (DE) genes, which were then used in unsupervised clustering analysis to identify patient subgroups. The prognostic value of the identified DE genes was then validated on formalin-fixed, paraffin-embedded (FFPE) samples. A total of 177 RNA samples were derived from 89 FF and 88 FFPE surgical tissues, of which 45 (51%) and 40 (45%), respectively, were from patients who developed LN+. We identified 6 DE genes overexpressed in LN+ tumors (false discovery rate <0.001; log fold change >1). Clustering analysis separated the patients into 2 subgroups (CM1, CM2), with CM2 exhibiting significantly increased expression and worse 5-y NFS rate (28%; P < 0.001). The prognostic value of these 6 candidate genes was validated on FFPE samples, which were also separated into 2 distinct prognostic groups, confirming the association between increased gene expression and poor 5-y NFS (CM1, 70.3%; CM2, 43.3%; P = 0.01). This is the first study identifying a panel of immune-related genes associated with NFS that can potentially be used clinically stratifying the risk of LN+ at the time of OSCC diagnosis.

KIF14 acts as a prognostic biomarker correlates with LCP2/ ITGAMN/ immune cell infiltration in oral squamous cell carcinoma

“…This evidence suggested our nding is accurate and novel. And then, GO analysis of these genes shows that they were particularly rich in immune-related biological processes and molecular functions (including lymphocyte activation, immune response activation, adaptive immune responses, as well as cell activation involved in immune response) (33). This study supports the critical participation of genes in the modules we screened in OSCC immunization activities.…”

Quantitative nuclear phenotype signatures predict nodal disease in oral squamous cell carcinoma

“…We also observed that the model performs with similar accuracy compared to the pathology of poorly differentiation. From our previous published data [ 26 ], we found that among the 569 cases with DOI information, cutoff at 3mm, 4mm, and 5mm provide 41.9%, 46.1%, and 48.7% accuracy in predicting the nodal disease, which potentially results in overtreatment for patients with no risk of nodal disease and undertreatment for those later showing nodal disease [ 10 ]. For well and moderately differentiated tumors, the accuracy of our data is much higher than the current approach using tumor DOI.…”

“…Patients were diagnosed with OSCC from oral anatomical sites, including C02.0 to C6.0 of the ICD-10 (International Statistical Classification of Disease and Related Health Problems); clinical node-negative at the time of initial diagnosis (cLN0); enrolled in the surgical trial and received intent-to-cure surgery as the primary treatment with or without END. As a pilot study, we identified 35 primary tumors that have previously analyzed and reported [ 26 , 27 ] and with enough tumor tissue for additional sections.…”

Identification of key survival genes of the tumor microenvironment and immune infiltration in head and neck squamous cell carcinoma

“…A subgroup of genetically distinct HPV-negative HNC with favorable prognoses was con rmed 2 ; however, the role and prognostic value of TME-related genes had not been fully elucidated. In oral cancer nodal disease (OCND), immune-related gene expression has prognostic value with regard to node-free survival (NFS) 24 . Lecerf et al retrospectively evaluated the expression of 46 immune-related genes and immune-cell subpopulation genes among 96 patients with HNSCC and concluded that overexpression of OX40L and PDGFRB was associated with poor outcomes 25 .…”