Semaphorin-3F/Neuropilin-2 Transcriptional Expression as a Predictive Biomarker of Occult Lymph Node Metastases in HNSCC

Simple Summary The presence of lymph neck node metastasis is the most important clinical prognostic factor in patients with head and neck squamous cell carcinoma. The expression of the semaphorin-3F and neuropilin-2 proteins is involved in the regulation of lymphangiogenesis. We analized the transcriptional expression of semaphorin-3F and neuropilin-2 in head and neck squamous cell carcinoma tumors of patients without clinical or radiology evidence of lymph node involvement treated with elective neck dissection. We found that patients with high semaphorin-3F and low neuropilin-2 had a lower risk of occult lymph node metastasis than the ones who had low semaphorin-3F or high semaphorin-3F and high neuropilin-2. If our results are validated, the expression of the SEMA3F-NRP2 axis could be used as a biomarker predicting the risk of occult lymph node metastasis, with elective neck dissections being indicated exclusively for patients at higher risk. The availability of a biomarker with the capacity to predict the presence of occult lymph node metastases would make it possible to avoid elective neck dissections in low-risk patients, with the consequent decrease in surgical time and morbidity of the treatment without impairing the oncologic outcome. The expression of the semaphorin-3F (SEMA3F) and neuropilin-2 (NRP2) is involved in the regulation of lymphangiogenesis. The present study analyzes the relationship between the transcriptional expression of the SEMA3F-NRP2 genes and the presence of occult lymph node metastases in patients with cN0 head and neck squamous cell carcinomas. We analyzed the transcriptional expression of SEMA3F and NRP2 in a cohort of 53 patients with cN0 squamous cell carcinoma treated with an elective neck dissection. Occult lymph node metastases were found in 37.7% of the patients. Patients with occult lymph node metastases (cN0/pN+) had significantly lower SEMA3F expression values than patients without lymph node involvement (cN0/pN0). Considering the expression of the SEMA3F-NRP2 genes, patients were classified into two groups according to the risk of occult nodal metastasis: Group 1 (n = 34), high SEMA3F/low NRP2 expression, with a low risk of occult nodal involvement (14.7% cN0/pN+); Group 2 (n = 19), low SEMA3F or high SEMA3F/high NRP2 expression, with a high risk of occult nodal involvement (78.9% cN0/pN+). Multivariate analysis showed that patients in Group 2 had a 26.2 higher risk of lymph node involvement than patients in Group 1. There was a significant relationship between the transcriptional expression values of the SEMA3F-NRP2 genes and the risk of occult nodal metastases.