STAT3 Found to be Associated with Adverse Clinical Outcomes in Colorectal Cancers

A model example of personalized cancer therapy that has demonstrated improved patient outcomes is the use of anti-HER2 treatment. Breast cancer patients screened via molecular diagnostics and identified as having amplification of the HER2 gene generally have a poorer prognosis, but show better responses to anti-HER2 treatment.

Structure of the STAT3 protein. Source: Wikimedia Commons user Emw

Identification of biomarkers that are both predictive of outcome and are good candidates for the development of targeted treatments is a major goal of oncology research. Recent studies in colorectal cancer patients have found that as many as 99% of patients harboring a KRAS mutation do not respond to EGFR antibody treatment. This type of tumor classification has a very high value in predicting outcomes and selecting appropriate treatment, but unfortunately, the development of predictive markers for most cancers is still in its infancy.

STAT3 Shows Potential as Prognostic Factor in Colorectal Cancer

In a paper published on February 10, 2011 in the online version of Clinical Cancer Research (doi:10.1158/1078-0432.CCR-10-2694), researchers from the Dana-Farber Cancer Institute and Harvard Medical Schools have identified the activated signal transducer and activator of transcription (STAT3) protein as a potential predictive marker in colorectal cancer. The large-scale, 724-patient study found that higher levels of the activated version of the STAT3 protein was associated with adverse clinical outcomes among colorectal cancer patients. This work supports further study of this molecular target as both a prognostic marker and a therapeutic target.

STAT3 is a transcription factor that is constitutively activated in some cancers and appears to play a role in many important cellular processes including cell division, survival, angiogenesis, and tumor-related inflammation. STAT3 has also been shown to thwart anti-tumor immune response. Whether STAT3 has utility as a prognostic factor in colorectal cancer has not been well studied with one previous small sample size study showing no association, two showing poor prognosis and one study showing better prognosis associated with activated STAT3.

The authors used a database of 724 colorectal cancer patients from two prospective studies that had clinical, pathological, and molecular data, including KRAS, BRAF, and PIK3CA mutation status to evaluate the relationship of these variables to activated STAT3 status to eliminate potential cofounding variables

The Results

18% of patients had high levels activated STAT3 expression. High levels of activated STAT3 were significantly associated with shorter cancer-specific survival and significantly higher colorectal cancer-specific mortality as compared to STAT3-negative cases. The study researchers did not find an significant modifying effects of other variables, including age, sex, BMI, family history of colorectal cancer, tumor location, stage, grade, and molecular mutations, on STAT3 expression status.

Activated STAT3 expression appears to be an independent prognostic factor for colorectal cancer and may serve as a prognostic marker for colorectal cancer patients in the future and for patient selection in future clinical trials when the results of this study are well validated.