Early cancer diagnosis is critical to survival. In a study designed to develop an easy and inexpensive early-warning test for cancer, we propose to evaluate a simple assay of a marker enzyme for predicting the presence of cancer. Using colorectal cancer as our model system, this research study will initially test whether expression levels of the active form of matrix metalloproteinase 2 (MMP-2) can be used to detect the presence of colorectal cancer and/or permit early detection of cancer recurrence. We propose to study this well-known cancer marker in innovative ways--i.e., for diagnosis or follow-up, rather than prognosis; in whole blood, rather than serum; and with a gel zymography assay that focuses on the active MMP-2 band as a """"""""master switch"""""""" and perhaps """"""""master marker"""""""" of malignancy. We have identified active MMP-2 gel banding patterns that distinguish colorectal cancers from control mucosa in 94/100 tissue extracts. We propose to test whether our results on tissues can be extrapolated to whole blood assays for early diagnosis of colorectal carcinomas or cancer recurrence. Screening of colorectal cancer patients and controls from the general population will be then compared to screening of other types of cancer patients, including those with common cancers, such as lung, breast or prostate cancer, as well as patients with a variety of noncancerous diseases, including common metabolic diseases, chronic inflammatory diseases and patients with other common medical conditions. Preliminary data indicate that MMP-2 patterns in whole blood samples will readily distinguish colorectal cancer patients from normal controls, from patients with a number of common non-cancerous diseases, including diverticulosis, asthma and diabetes and from some patients tested thus far with other types of cancer. Our proposed 2-year exploratory study is designed to establish the sensitivity and specificity of this blood assay for detection of colorectal cancer versus other cancers and non-cancerous diseases and to test its sensitivity for detection of cancer recurrences following surgical resection and treatment. These analyses will permit us to standardize and evaluate a new methodology for cancer diagnosis and followup with the long-term goals being an improvement in cancer screening methods for the general population and an optimization of patient followup once cancer has been diagnosed.
| Murnane, Mary Jo; Cai, Jinguo; Shuja, Sania et al. (2011) Active matrix metalloproteinase-2 activity discriminates colonic mucosa, adenomas with and without high-grade dysplasia, and cancers. Hum Pathol 42:688-701 |
| Murnane, Mary Jo; Cai, Jinguo; Shuja, Sania et al. (2009) Active MMP-2 effectively identifies the presence of colorectal cancer. Int J Cancer 125:2893-902 |
