Study Examines Protein Expression Biomarkers in HPV-Negative Squamous Cell Carcinomas of the Head and Neck
A quartet of proteins that play critical roles in cell replication, cell death, and DNA repair could lead to better targets for therapy against treatment-resistant head and neck squamous cell cancers. In a study presented this week at the American Association for Cancer Research (AACR) Annual Meeting 2014, researchers showed a correlation between the expression levels of these proteins in human papillomavirus (HPV)-negative head and neck cancers, which have a poorer prognosis than HPV-positive tumors.
Head and neck cancers that are HPV-negative have a poorer prognosis than those that are HPV-positive. According to the National Cancer Institute, approximately 75% of head and neck cancers are caused by tobacco and alcohol use, and use of the two together are a greater risk than either factor alone. This study’s findings could help determine potential treatments for head and neck cancers.
“The ultimate goal would be to better understand a tumor’s protein signature and underlying biology so that, in the future, we can better understand treatments are more likely to be beneficial to our patients with head and neck cancer,” said Ranee Mehra, MD, of Fox Chase Cancer Center, who presented the study.
Study Details
Dr. Mehra and colleagues looked at protein expression levels in samples from 101 cases of head and neck cancer banked from 1990 to 2002 in the Fox Chase tissue repository. One advantage of using this tissue, Dr. Mehra said, is that samples are cross-referenced with patient treatment and survival data. Using tissue microarrays, the team looked for expression of ERCC-1, a DNA repair protein; survivin, a protein that inhibits programmed cell death or apoptosis; and two proteins active during cell division, Aurora A and phospho-Aurora A.
The research showed positive associations between expression of the repair protein ERCC1 and each cell-division protein, AuroraA (P < .0001) and phospho-Aurora (P = .0027). It also showed an association between both Aurora proteins (P < .0001). There was also an association between the apoptosis-regulator, survivin, and Aurora A (P = .0064), as well as survivin and ERCC1 (P = .0084).
A review of a publically available database examining mRNA expression levels for the four proteins showed a highly significant correlation between Aurora A and survivin (P = .002), confirming the protein microarray findings.
Potential Biomarkers for Survival
Survivin expression may prove to be a marker for improved survival, especially in patients who were treated with surgery plus radiation, Dr. Mehra said. She found that tumors with less than a median level of survivin expression were associated with improved patient survival compared to tumors with more than a median level of survivin (P = .03).
ERCC1 is already a potential prognostic biomarker for survival among patients treated with radiation after surgery. In a study published in Clinical Cancer Research last year, Dr. Mehra and colleagues found lower levels of ERCC1 predicted improved survival among patients treated with radiation.
"We hope to understand how these various pathways and mechanisms interrelate with each others. Understanding those pathways would help guide future research," Dr. Mehra said.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
