Prognostic value of Annexin A3 in human colorectal cancer and its correlation with hypoxia-inducible factor-1α

Abstract

Annexins are a family of intracellular proteins that bind membrane phospholipids in a Ca²⁺ concentration-dependent manner and are involved in cellular processes, including apoptosis, proliferation and differentiation. Hypoxia-inducible factor-1α (HIF-1α) has been hypothesized to be critical in the angiogenesis of tumors. We hypothesized that Annexin A3, a member of the Annexin family, and HIF-1α may be associated with each other in colorectal cancer. The expression of Annexin A3 and HIF-1α in 60 colorectal cancer tissues was assessed by immunohistochemistry to statistically analyze the association between the clinicopathological features and survival of these cases. In the present study, 65 and 47% of colorectal cancer specimens were found to show Annexin A3 and HIF-1α immunoreactivity, respectively. Annexin A3 expression was found to significantly correlate with tumor size and Dukes' stage (all P<0.05). Furthermore, Annexin A3 and HIF-1α protein expression exhibited a similar pattern in these samples, and their expression was found to correlate with poor survival in colorectal cancer patients. The results of the current study indicated for the first time that the increased expression of Annexin A3 in colorectal cancer correlates significantly with tumor growth and poor prognosis. Furthermore, Annexin A3 has been found to correlate with HIF-1α expression. These observations highlight an improved understanding of the carcinogenesis of colorectal cancer.

Keywords: Annexin A3; colorectal cancer; hypoxia-inducible factor-1α; immunohistochemistry; prognosis.

Figure 1

Immunohistochemical staining of Annexin A3 in colorectal cancer. (A) Staining for Annexin A3 protein was stronger in tumor (T) tissue than in adjacent noncancerous (N) tissue. Positive Annexin A3 staining in (B) well-differentiated and (C) moderately differentiated colorectal cancer and (D) lymph nodes, indicated by the arrows (labeled streptavidin-biotin staining; magnification, ×200).

Figure 2

Immunohistochemical analysis of Annexin A3 and HIF-1α proteins in the same colorectal cancer samples. Positive staining for (A–C) Annexin A3 and (D–F) HIF-1α in the cytoplasm of colorectal cancer cells. HIF-1α, hypoxia-inducible factor-1α (labeled streptavidin-biotin staining; magnification, ×200).

Figure 3

Kaplan-Meier analysis of overall survival curves of colorectal cancer patients, according to the expression of (A) Annexin A3 and (B) HIF-1α. HIF-1α, hypoxia-inducible factor-1α.