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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

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

Wada Yuma Y Morine Yuji Y Imura Satoru S Ikemoto Tetsuya T Saito Yu Y Takasu Chie C Yamada Shinichiro S Shimada Mitsuo M

World journal of surgical oncology 20200907 1

<h4>Background</h4>The role of hypoxia-inducible factor-1α (HIF-1α) in primary colorectal cancer (CRC) and colorectal liver metastasis (CRLM) has remained unclear. The aim of this study was to investigate HIF-1α expression and its association with prognosis in patients with CRLM with a focus on hepatic stellate cells (HSCs).<h4>Methods</h4>Colon cancer cells were cultured in HSC-conditioned medium (CM), and HIF-1α expression and cell migration were analyzed. Seventy-five patients with CRLM who u ...[more]

PMID: 32895059

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Project description:BACKGROUND:Adjuvant endocrine treatment improves survival after estrogen receptor (ER) positive breast cancer. Recurrences occur, and most patients with metastatic breast cancer develop treatment resistance and incurable disease. An influential factor in relation to endocrine treatment resistance is tumor hypoxia and the hypoxia inducible transcription factors (HIFs). Poor perfusion makes tumors hypoxic and induces the HIFs, which promote cell survival. We previously showed that hypoxic breast cancer cells are tamoxifen-resistant, and that HIF-inhibition restored tamoxifen-sensitivity. We found that HIF-induced tamoxifen-resistance involve cross-talk with epithelial growth factor receptor (EGFR), which itself is linked to tamoxifen resistance. Contralateral breast cancer (CBC), i.e. development of a second breast cancer in the contralateral breast despite adjuvant tamoxifen treatment is in essence a human in vivo-model for tamoxifen-resistance that we explore here to find molecular pathways of tamoxifen-resistance. METHODS:We constructed a tissue-microarray including tumor-tissue from a large well-defined cohort of CBC-patients, a proportion of which got their second breast cancer despite ongoing adjuvant therapy. Using immunohistochemistry >500 patients were evaluable for HIF-1α and EGFR in both tumors, and correlations to treatment, patient outcome, prognostic and predictive factors were analyzed. RESULTS:We found an increased proportion of HIF-1α-positive tumors in tamoxifen-resistant (CBC during adjuvant tamoxifen) compared to naïve tumors (CBC without prior tamoxifen). Tumor HIF-1α-positivity correlated to increased breast cancer mortality, and negative prognostic factors including low age at diagnosis and ER-negativity. There was a covariance of HIF-1α- and EGFR-expression and also EGFR-expression correlated to poor prognosis. CONCLUSIONS:The increased percentage of HIF-1α-positive tumors formed during adjuvant tamoxifen suggests a role for HIF-1α in escaping tamoxifen's restraining effects on breast cancer. Implicating a potential benefit of HIF-inhibitors in targeting breast cancers resistant to endocrine therapy.

Dataset Information

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

Publications

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

Similar Datasets

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