Identification of FOXP1 as a favorable prognostic biomarker and tumor suppressor in intrahepatic cholangiocarcinoma
Abstract Background Forkhead-box protein P1 (FOXP1) has been proposed to have both oncogenic and tumor-suppressive properties, depending on tumor heterogeneity. However, the role of FOXP1 in intrahepatic cholangiocarcinoma (ICC) has not been previously reported. Methods Immunohistochemistry was perf...
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BMC
2024-01-01
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Online Access: | https://doi.org/10.1186/s12885-024-11882-x |
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author | Chenwei Tang Hongkai Zhuang Huanjun Tong Xiaopeng Yu Jialu Chen Qingbin Wang Xiaowu Ma Bingkun Wang Yonglin Hua Changzhen Shang Zhaohui Tang |
author_facet | Chenwei Tang Hongkai Zhuang Huanjun Tong Xiaopeng Yu Jialu Chen Qingbin Wang Xiaowu Ma Bingkun Wang Yonglin Hua Changzhen Shang Zhaohui Tang |
author_sort | Chenwei Tang |
collection | DOAJ |
description | Abstract Background Forkhead-box protein P1 (FOXP1) has been proposed to have both oncogenic and tumor-suppressive properties, depending on tumor heterogeneity. However, the role of FOXP1 in intrahepatic cholangiocarcinoma (ICC) has not been previously reported. Methods Immunohistochemistry was performed to detect FOXP1 expression in ICC and normal liver tissues. The relationship between FOXP1 levels and the clinicopathological characteristics of patients with ICC was evaluated. Finally, in vitro and in vivo experiments were conducted to examine the regulatory role of FOXP1 in ICC cells. Results FOXP1 was significantly downregulated in the ICC compared to their peritumoral tissues (p < 0.01). The positive rates of FOXP1 were significantly lower in patients with poor differentiation, lymph node metastasis, invasion into surrounding organs, and advanced stages (p < 0.05). Notably, patients with FOXP1 positivity had better outcomes (overall survival) than those with FOXP1 negativity (p < 0.05), as revealed by Kaplan–Meier survival analysis. Moreover, Cox multivariate analysis showed that negative FOXP1 expression, advanced TNM stages, invasion, and lymph node metastasis were independent prognostic risk factors in patients with ICC. Lastly, overexpression of FOXP1 inhibited the proliferation, migration, and invasion of ICC cells and promoted apoptosis, whereas knockdown of FOXP1 had the opposite role. Conclusion Our findings suggest that FOXP1 may serve as a novel outcome predictor for ICC as well as a tumor suppressor that may contribute to cancer treatment. |
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spelling | doaj.art-edc83ac894c54efa8562c2f01e2f90fb2024-03-05T16:32:47ZengBMCBMC Cancer1471-24072024-01-0124111310.1186/s12885-024-11882-xIdentification of FOXP1 as a favorable prognostic biomarker and tumor suppressor in intrahepatic cholangiocarcinomaChenwei Tang0Hongkai Zhuang1Huanjun Tong2Xiaopeng Yu3Jialu Chen4Qingbin Wang5Xiaowu Ma6Bingkun Wang7Yonglin Hua8Changzhen Shang9Zhaohui Tang10Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of General Surgery, Xinhua Hospital Affiliated to Medical College of Shanghai Jiaotong UniversityDepartment of General Surgery, Xinhua Hospital Affiliated to Medical College of Shanghai Jiaotong UniversityDepartment of General Surgery, Xinhua Hospital Affiliated to Medical College of Shanghai Jiaotong UniversityDepartment of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of General Surgery, Xinhua Hospital Affiliated to Medical College of Shanghai Jiaotong UniversityAbstract Background Forkhead-box protein P1 (FOXP1) has been proposed to have both oncogenic and tumor-suppressive properties, depending on tumor heterogeneity. However, the role of FOXP1 in intrahepatic cholangiocarcinoma (ICC) has not been previously reported. Methods Immunohistochemistry was performed to detect FOXP1 expression in ICC and normal liver tissues. The relationship between FOXP1 levels and the clinicopathological characteristics of patients with ICC was evaluated. Finally, in vitro and in vivo experiments were conducted to examine the regulatory role of FOXP1 in ICC cells. Results FOXP1 was significantly downregulated in the ICC compared to their peritumoral tissues (p < 0.01). The positive rates of FOXP1 were significantly lower in patients with poor differentiation, lymph node metastasis, invasion into surrounding organs, and advanced stages (p < 0.05). Notably, patients with FOXP1 positivity had better outcomes (overall survival) than those with FOXP1 negativity (p < 0.05), as revealed by Kaplan–Meier survival analysis. Moreover, Cox multivariate analysis showed that negative FOXP1 expression, advanced TNM stages, invasion, and lymph node metastasis were independent prognostic risk factors in patients with ICC. Lastly, overexpression of FOXP1 inhibited the proliferation, migration, and invasion of ICC cells and promoted apoptosis, whereas knockdown of FOXP1 had the opposite role. Conclusion Our findings suggest that FOXP1 may serve as a novel outcome predictor for ICC as well as a tumor suppressor that may contribute to cancer treatment.https://doi.org/10.1186/s12885-024-11882-xIntrahepatic cholangiocarcinomaImmunohistochemistryOutcome predictionProtein biomarker |
spellingShingle | Chenwei Tang Hongkai Zhuang Huanjun Tong Xiaopeng Yu Jialu Chen Qingbin Wang Xiaowu Ma Bingkun Wang Yonglin Hua Changzhen Shang Zhaohui Tang Identification of FOXP1 as a favorable prognostic biomarker and tumor suppressor in intrahepatic cholangiocarcinoma BMC Cancer Intrahepatic cholangiocarcinoma Immunohistochemistry Outcome prediction Protein biomarker |
title | Identification of FOXP1 as a favorable prognostic biomarker and tumor suppressor in intrahepatic cholangiocarcinoma |
title_full | Identification of FOXP1 as a favorable prognostic biomarker and tumor suppressor in intrahepatic cholangiocarcinoma |
title_fullStr | Identification of FOXP1 as a favorable prognostic biomarker and tumor suppressor in intrahepatic cholangiocarcinoma |
title_full_unstemmed | Identification of FOXP1 as a favorable prognostic biomarker and tumor suppressor in intrahepatic cholangiocarcinoma |
title_short | Identification of FOXP1 as a favorable prognostic biomarker and tumor suppressor in intrahepatic cholangiocarcinoma |
title_sort | identification of foxp1 as a favorable prognostic biomarker and tumor suppressor in intrahepatic cholangiocarcinoma |
topic | Intrahepatic cholangiocarcinoma Immunohistochemistry Outcome prediction Protein biomarker |
url | https://doi.org/10.1186/s12885-024-11882-x |
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