Colorectal cancer is a notorious disease, with almost half of the patients succumbing to the disease. The prevalence and incidence rates of
colorectal cancer are increasing in many parts of the world, highlighting the need to discover new
biomarkers for diagnosis and
therapy.
Caldesmon (CaD), an
actin-binding protein that plays a significant role in controlling cell motility, has emerged as a promising
biomarker. The CALD1 gene encodes CaD as multiple transcripts that mainly encode two
protein isoforms: High-molecular-weight (h-CaD), expressed in smooth muscle, and low-molecular-weight (l-CaD), expressed in nonsmooth muscle cells. Most studies have suggested an oncogenic role of CaD in
colorectal cancer, but the exact subcellular localization of the two CaD
isoforms in
tumor cells and stroma have not been clarified yet. Here, we analyzed tissue samples from 262
colorectal cancer patients by immunohistochemistry analysis using specific
antibodies for l-CaD and h-CaD. The results showed elevated cytoplasmic expression levels of l-Cad in 187/262 (71.4%) cases. l-Cad was expressed at low levels in the normal colon mucosa and was also consistently expressed in the
cancer-associated stroma of all cases, suggesting that it could play a role in modulating the tumor microenvironment. l-CaD expression in
cancer cells was associated with preinvasive stages of
cancer. Survival analysis indicated that patients with high l-CaD expression in
tumor cells could respond poorly to selective chemotherapeutic
5FU, but not
combination chemotherapy. h-CaD was expressed in colonic and vascular smooth muscle cells as expected and to a lesser extent in the
tumor-associated stroma, but it was not expressed in the
cancer cells or normal colon mucosal epithelial cells. Collectively, these data clarify how the expression patterns of CaD
isoforms in
colorectal cancer can have applications in the management of
colorectal cancer patients.