HIF-1? expression in liver metastasis but not primary colorectal cancer is associated with prognosis of patients with colorectal liver metastasis.

ABSTRACT: BACKGROUND:The role of hypoxia-inducible factor-1? (HIF-1?) in primary colorectal cancer (CRC) and colorectal liver metastasis (CRLM) has remained unclear. The aim of this study was to investigate HIF-1? expression and its association with prognosis in patients with CRLM with a focus on hepatic stellate cells (HSCs). METHODS:Colon cancer cells were cultured in HSC-conditioned medium (CM), and HIF-1? expression and cell migration were analyzed. Seventy-five patients with CRLM who underwent an initial curative hepatectomy were enrolled. We examined HIF-1? expressions and patient prognosis between primary CRCs and the matched liver metastatic specimens. RESULTS:Activated HSCs induced HIF-1? mRNA and protein expression in colon cancer cells (p < 0.01) and promoted cell migration (p < 0.01). The positive rates of HIF-1? expression in primary CRCs and liver metastases were 68.0 and 72.0%, respectively. There were no differences in overall (OS) and disease-free survival (DFS) of HIF-1? expression in primary CRC. However, HIF-1? expression in liver metastasis correlated to poor prognosis in both OS and DFS. Furthermore, patients with HIF-1? positive expression in liver metastasis had poor prognosis. CONCLUSION:HIF-1? expression in liver metastasis determines poor prognosis of CRLM patients. HSCs might play a key role in aggressive phenotypes of tumor cells.

SUBMITTER: Wada Y 

PROVIDER: S-EPMC7487629 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature