Dataset Information

HIF-1α 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-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).

Methods

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 underwent an initial curative hepatectomy were enrolled. We examined HIF-1α expressions and patient prognosis between primary CRCs and the matched liver metastatic specimens.

Results

Activated HSCs induced HIF-1α mRNA and protein expression in colon cancer cells (p < 0.01) and promoted cell migration (p < 0.01). The positive rates of HIF-1α 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-1α expression in primary CRC. However, HIF-1α expression in liver metastasis correlated to poor prognosis in both OS and DFS. Furthermore, patients with HIF-1α positive expression in liver metastasis had poor prognosis.

Conclusion

HIF-1α 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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Publications

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:BackgroundSurgery is an important means for patients with colorectal liver metastases (CRLM) to improve their long-term survival, and accurate screening of high-risk factors is crucial to guiding postoperative monitoring and treatment. With this in mind, the aim of this study was to investigate the expression levels and prognostic roles of Mismatch Repair (MMR), Ki67, and Lymphovascular invasion(LVI) in the tumor tissues of colorectal of CRLM.Methods85 Patients with CRLM who received surgical treatment for liver metastases after colorectal cancer resection from June, 2017 and Jan, 2020 were included in this study. Independent risk factors affecting the survival of patients with CRLM were investigated using a Cox regression model and the Kaplan-Meier method, and a nomogram for predicting the OS of patients with CRLM was established according to a Cox multivariate regression model. Calibration plots and Kaplan-Meier curves were used to assess the performance of the nomogram.ResultsThe median survival time was 39 months (95% CI: 32.05-45.950), and MMR, Ki67 and LVI were significantly correlated with prognosis. Univariate analysis indicated that larger metastasis size (p=0.028), more than one liver metastases (p=0.001),higher serum CA199 (p<0.001), N1-2 stage (p<0.001), the presence of LVI (p=0.001), higher Ki67 (p<0.001), and pMMR predicted worse OS. In addition, synchronous liver metastasis (p = 0.008), larger metastasis size (p=0.02), more than one liver metastases (p<0.001),higher serum CA199 (p<0.001), the presence of LVI (p=0.001), nerve invasion (p=0.042) higher Ki67 (p=0.014), and pMMR (p=0.038) were each associated with worse DFS. Multivariate analysis indicated that higher serum CA199 (HR = 2.275, 95%CI: 1.302-3.975 p=0.004), N1-2 stage(HR = 2.232, 95%CI: 1.239-4.020 p=0.008), the presence of LVI (HR = 1.793, 95%CI: 1.030-3.121 p=0.039), higher Ki67 (HR = 2.700, 95%CI: 1.388-5.253\ p=0.003), and pMMR (HR = 2.213, 95%CI: 1.181-4.993 p=0.046) all predicted worse OS. Finally, synchronous liver metastasis (HR = 2.059, 95%CI: 1.087-3.901 p=0.027), more than one liver metastases ((HR =2.025, 95%CI: 1.120-3.662 p=0.020),higher serum CA199 (HR =2.914, 95%CI: 1.497-5.674 p=0.002), present LVI (HR = 2.055, 95%CI: 1.183-4.299 p=0.001), higher Ki67 (HR = 3.190, 95%CI: 1.648-6.175 p=0.001) and pMMR(HR = 1.676, 95%CI: 1.772-3.637 p=0.047) predicted worse DFS, and the nomogram achieved an effective level of predictive ability.ConclusionThis study showed that MMR, Ki67, and Lymphovascular invasion were independent risk factors for the postoperative survival of CRLM patients, and a nomogram model was constructed to predict the OS of these patients after liver metastasis surgery. These results can help surgeons and patients to develop more accurate and individualized follow-up strategies and treatment plans after this surgery.

Dataset Information

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

Background

Methods

Results

Conclusion

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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