Elevated LSD1 and SNAIL Expression Indicate Poor Prognosis in Hypopharynx Carcinoma

Abstract

Head and neck squamous cell carcinomas (HNSCC) are among the most common cancers worldwide and are associated with a poor prognosis for patients. Among HNSCC, those originating in the hypopharynx have the worst prognosis. The histone demethylase LSD1 has been shown to promote cancer initiation, progression, and relapse through various mechanisms and is upregulated in many cancer tissues. LSD1 physically interacts with SNAIL and is required for SNAIL mediated transcriptional repression. Previous studies of the prognostic value of LSD1 in HNSCC have been limited in their analysis of sub-sites, and a correlation between LSD1 and SNAIL has not been shown in HNSCC patient samples. Here we used a large, representative, and clinically well-characterized cohort of 339 HNSCC patients to investigate the co-expression of LSD1 and SNAIL and their prognostic value in all HNSCC using immunohistochemical staining. Elevated LSD1 expression correlated with advanced tumor stage and poor progression-free survival (PFS) in HNSCC originating in the hypopharynx. Overexpression of the transcription factor SNAIL independently correlated with worse overall survival (OS) and PFS in HNSCC in general and prominently in tumors of the hypopharynx. Furthermore, increased LSD1 expression significantly correlated with elevated SNAIL expression in patient samples. Therefore, the presented data implicates LSD1 and SNAIL as independent prognostic biomarkers.

TRIM21 Expression as a Prognostic Biomarker for Progression-Free Survival in HNSCC

“…We analyzed TRIM21 expression in HNSCC specimens derived from a cohort of 419 patients diagnosed between 2012 and 2015 at the Institute of Pathology of the University Medical Center Schleswig-Holstein, Germany, as reported previously [ 13 , 34 , 35 , 36 , 37 , 38 , 39 ]. Tumor samples were derived from PTs, LMs, RTs and DMs.…”

Zinc finger proteins and ATP‐binding cassette transporter‐dependent multidrug resistance

“…Previous studies demonstrated that overexpression of SNAIL is associated with poor prognosis in patients with hypopharynx carcinoma and breast cancer 47,48 . The mechanistic role of SNAIL attributed to MDR is expected to be better understood in light of the role of the EMT 39 .…”

“…46 Previous studies demonstrated that overexpression of SNAIL is associated with poor prognosis in patients with hypopharynx carcinoma and breast cancer. 47,48 The mechanistic role of SNAIL attributed to MDR is expected to be better understood in light of the role of the EMT. 39 A review of the previous studies reveals that SNAIL overexpression increases the risk of chemoresistance, as evidenced by in vitro experiments 5-fluorouracil-resistant breast cancer cells, 49 and cisplatin-resistant ovarian cancer cells.…”

Histone Demethylase Modulation: Epigenetic Strategy to Combat Cancer Progression

“…For instance, KDM1 is overexpressed in bladder carcinomas but exhibits significantly decreased proliferation when treated with small interfering RNA (siRNA) matching to the KDM1 gene. The overexpression and carcinogenic activities of KDM1 have been also reported in breast, colorectal, liver, lung, hypopharynx, and prostate, cancers [ 56 , 57 , 58 , 59 , 60 , 61 , 62 ]. This renders key candidature to LSD1/KDM1 as a possible cancer therapeutic.…”