The prognostic implications of hypoxia-inducible factors in patients with colorectal cancer

This study investigated the prognostic value of hypoxia-inducible factor-1a and hypoxia-inducible factor-2a and their association with different clinicopathological features in patients with colorectal cancer. 

Cancer of the colon and rectum (colorectal cancer) is the third most prevalent malignancy worldwide. Growing evidence suggests that hypoxia plays a key role in progression of colorectal cancer. Hypoxia is the deprivation of oxygen from tissues and organs, and  a tumor becomes hypoxic when it outgrows its blood supply. Hypoxia encourages the formation of new blood vessels to supply the tumor with oxygen and consequently contributes to metastasis (the spread of cancer to distant organs via the blood circulation). Hypoxia-inducible factors (HIFs) are produced by hypoxic cells to facilitate the growth of these new blood vessels.  Two subtypes called HIF- 1a and HIF-2a are can be detected to measure tumor oxygen levels. While past studies have showed that HIF expression has some prognostic value in cancer, results in colorectal cancer are inconclusive.

This article examined the effect of HIF-1a and HIF-2a on prognosis and survival in patients with colorectal cancer.

This review analyzed results from 23 studies, including 2984 patients with colorectal cancer. The main parameters evaluated were overall survival (the percentage of patients who survived for a defined period of time) and disease free survival (the period after curative treatment when no disease can be detected). In addition, the article evaluated the relationship between overexpression of HIF-1a and HIF-2a and different clinicopathological features, i.e. signs and symptoms of the disease as well as tumor tissue features.

Results showed that overexpressed HIFs were associated with worse overall survival and reduced disease-free survival (surviving without cancer). Overexpression of HIF-1a carried twice the risk of mortality compared to normal expression. Overexpression of HIF-1a carried almost three times the risk of survival with cancer (as opposed to survival without cancer) compared to normal expression. Both overexpression of HIF-1a andHIF-2a were associated with a worse prognosis for colorectal cancer.

 HIF-1a overexpression was significantly associated with worse clinicopathological features, such as cancer invasion, lymph node involvement and metastasis. The sole significant relationship found with overexpression of HIF-2a was with grade of differentiation (an evaluation of how much or how little tumor cells resemble normal cells, with a higher grade indicating a worse prognosis).

Overall, overexpressed HIF was significantly associated with increased mortality risk and unfavorable prognosis in patients with colorectal cancer. Both HIF-1 and HIF-2 were associated with distinct clinicopathologic features.

The studies included for analysis were only accepted if written in English or Chinese, which may have introduced bias.