Biomarker Tied to Poor Survival for Colorectal Cancer Patients

Biomarkers for predicting prognosis are critical to treating colorectal cancer (CRC) patients, and a subunit of a signalosome is overexpressed in CRC samples and that overexpression is correlated with poor patient survival.

Colorectal cancer is a leading cause of mortality and the primary treatment for patients is surgery and conventional cytotoxic chemotherapy and/or targeted therapies are routinely used to treat patients who are at high risk of developing recurrent or metastatic disease as CRC.

Scientists at the University of Texas M.D. Anderson Cancer (Houston, TX, USA) working with their Chinese colleagues obtained snap-frozen tissue samples from 20 CRC patients with stage III disease. Thirty-three fresh frozen paired samples of primary CRC and adjacent normal colon tissue were collected from patients who had stage II or stage III disease at the time of specimen collection. They also obtained paraffin-embedded samples of primary colorectal adenocarcinomas from two different cohorts.

The team used a multiplicity of techniques in their study including microarray analysis, transfection and generation of stable transfectants, and real-time polymerase chain reaction (qRT-PCR) that was performed using a 7500 Real-Time PCR System (Applied Biosystems; Foster, City, CA, USA). Other methodologies used were Western Blot analysis and immunoprecipitation, ubiquitination and turnover assays, and luciferase reporter gene assays.

The study revealed that CSN6, a subunit of a protein complex known as constitutive photomorphogenesis 9 (COP9) signalsome, was overexpressed in colorectal cancer tissue samples. The biomarker is normally regulated through signaling pathways called epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinases (ERK). When CSN6 is overexpressed via ERK2 in particular, however, it can lead to deregulation of another protein, beta-catenin, and a transcription factor known to be linked to cancer development. The finding could be significant in the search for alternative treatment strategies for colorectal cancer.

Mong-Hong Lee, PhD, a professor of Molecular and Cellular Oncology and a senior coauthor of the study said, “CSN6 is a biomarker that is elevated in colon cancer and leads to worse recurrence-free survival. This occurs when CSN6 is deregulated through a series of cellular signaling pathways. Our findings indicated that deregulation of CSN6 by ERK2 resulted in stabilization and activation of beta-catenin, which is important for colorectal cancer development. Defining the molecular alterations in colorectal cancer can help guide treatment and improve clinical care.” The study was published on August 10, 2015, in the journal Cancer Cell.

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University of Texas M.D. Anderson Cancer 
Applied Biosystems