HighRAB25expression is associated with good clinical outcome in patients with locally advanced head and neck squamous cell carcinoma

Abstract

Currently there are no molecular markers able to predict clinical outcome in locally advanced head and neck squamous cell carcinoma (HNSCC). In a previous microarray study, RAB25 was identified as a potential prognostic marker. The aim of this study was to analyze the association between RAB25 expression and clinical outcome in patients with locally advanced HNSCC treated with standard therapy. In a retrospective immunohistochemical study (n = 97), we observed that RAB25-negative tumors had lower survival (log-rank, P = 0.01) than patients bearing positive tumors. In an independent prospective mRNA study (n = 117), low RAB25 mRNA expression was associated with poor prognosis. Using classification and regression tree analysis (CART) we established two groups of patients according to their RAB25 mRNA level and their risk of death. Low mRNA level was associated with poor local recurrence-free (log-rank, P = 0.005), progression-free (log-rank, P = 0.002) and cancer-specific (log-rank, P < 0.001) survival. Multivariate Cox model analysis showed that low expression of RAB25 was an independent poor prognostic factor for survival (hazard ratio: 3.84, 95% confidence interval: 1.93–7.62, P < 0.001). Patients whose tumors showed high RAB25 expression had a low probability of death after treatment. We also found lower RAB25 expression in tumors than in normal tissue (Mann–Whitney U, P < 0.001). Moreover, overexpression of RAB25 in the UM-SCC-74B HNSCC cell line increased cisplatin sensitivity, and reduced cell migration and invasion. Our findings support a tumor suppressor role for RAB25 in HNSCC and its potential use to identify locally advanced patients with a high probability of survival after genotoxic treatment.

Loss of Rab25 promotes the development of skin squamous cell carcinoma through the dysregulation of integrin trafficking

“…In tumors originating from HNSCC , oral SCC , oropharyngeal SCC, and esophageal SCC , the tumor suppressor effects of Rab25 are well established. This conclusion is supported by a positive prognosis for high Rab25 expression in patients with HNSCC . However, the role of Rab25 in the squamous epithelia of the skin has remained unknown.…”

The combined use of EFS, GPX2, and SPRR1A expression could distinguish favorable from poor clinical outcome among epithelial‐like head and neck carcinoma subtypes

“…UM‐SCC‐22A, UM‐SCC‐22B, UM‐SCC‐74B, FaDu, SCC9, and SCC25 HNSCCs cell lines were grown according to previously described methods and authenticated by comparing their Short Tandem Repeat (STR) profiles with the original reported profiles using the Cell ID kit (Promega Corporation, Madison, Wisconsin, USA) . OKF6‐tert1 keratinocytes were obtained from the Cell Culture Core of the Harvard Skin Disease Research Center (http://www.rheinwaldlab.bwh.harvard.edu) and cultured in Keratinocyte Serum Free Medium (KSM) as previously described .…”

“…UM‐SCC‐22A, UM‐SCC‐22B, UM‐SCC‐74B, FaDu, SCC9, and SCC25 HNSCCs cell lines were grown according to previously described methods and authenticated by comparing their Short Tandem Repeat (STR) profiles with the original reported profiles using the Cell ID kit (Promega Corporation, Madison, Wisconsin, USA) . OKF6‐tert1 keratinocytes were obtained from the Cell Culture Core of the Harvard Skin Disease Research Center (http://www.rheinwaldlab.bwh.harvard.edu) and cultured in Keratinocyte Serum Free Medium (KSM) as previously described . Immunostaining was performed using the EnVision FLEX and FLEX+ Visualization System (Dako, Agilent Technologies, Santa Clara, California, USA) and the following antibodies: E‐cadherin (1:100, clone 36, BD Bioscience, Franklin Lakes, NJ, USA), N‐cadherin (1:50, clone 6G11, Dako, Agilent Technologies) and Vimentin (1:500, clone V9, Dako, Agilent Technologies) .…”

“…OKF6‐tert1 keratinocytes were obtained from the Cell Culture Core of the Harvard Skin Disease Research Center (http://www.rheinwaldlab.bwh.harvard.edu) and cultured in Keratinocyte Serum Free Medium (KSM) as previously described . Immunostaining was performed using the EnVision FLEX and FLEX+ Visualization System (Dako, Agilent Technologies, Santa Clara, California, USA) and the following antibodies: E‐cadherin (1:100, clone 36, BD Bioscience, Franklin Lakes, NJ, USA), N‐cadherin (1:50, clone 6G11, Dako, Agilent Technologies) and Vimentin (1:500, clone V9, Dako, Agilent Technologies) . Migration assays were performed using 8‐μm pore size transwell chambers (Corning.…”

Rab25 acts as an oncogene in luminal B breast cancer and is causally associated with Snail driven EMT

“…Rab25 expression also correlates with cancer stem cell-like populations in a subset of cancers [40]. However, in head and neck tumors and esophageal cancers, the loss of Rab25 drives tumorigenesis [25, 41]. Additionally, in colon cancer models, Rab25 exhibits a tumor suppressive function [29].…”