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...

Full description

Bibliographic Details
Main Authors: Chenwei Tang, Hongkai Zhuang, Huanjun Tong, Xiaopeng Yu, Jialu Chen, Qingbin Wang, Xiaowu Ma, Bingkun Wang, Yonglin Hua, Changzhen Shang, Zhaohui Tang
Format: Article
Language:English
Published: BMC 2024-01-01
Series:BMC Cancer
Subjects:
Online Access:https://doi.org/10.1186/s12885-024-11882-x
_version_ 1797276510910939136
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.
first_indexed 2024-03-07T15:29:13Z
format Article
id doaj.art-edc83ac894c54efa8562c2f01e2f90fb
institution Directory Open Access Journal
issn 1471-2407
language English
last_indexed 2024-03-07T15:29:13Z
publishDate 2024-01-01
publisher BMC
record_format Article
series BMC Cancer
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
work_keys_str_mv AT chenweitang identificationoffoxp1asafavorableprognosticbiomarkerandtumorsuppressorinintrahepaticcholangiocarcinoma
AT hongkaizhuang identificationoffoxp1asafavorableprognosticbiomarkerandtumorsuppressorinintrahepaticcholangiocarcinoma
AT huanjuntong identificationoffoxp1asafavorableprognosticbiomarkerandtumorsuppressorinintrahepaticcholangiocarcinoma
AT xiaopengyu identificationoffoxp1asafavorableprognosticbiomarkerandtumorsuppressorinintrahepaticcholangiocarcinoma
AT jialuchen identificationoffoxp1asafavorableprognosticbiomarkerandtumorsuppressorinintrahepaticcholangiocarcinoma
AT qingbinwang identificationoffoxp1asafavorableprognosticbiomarkerandtumorsuppressorinintrahepaticcholangiocarcinoma
AT xiaowuma identificationoffoxp1asafavorableprognosticbiomarkerandtumorsuppressorinintrahepaticcholangiocarcinoma
AT bingkunwang identificationoffoxp1asafavorableprognosticbiomarkerandtumorsuppressorinintrahepaticcholangiocarcinoma
AT yonglinhua identificationoffoxp1asafavorableprognosticbiomarkerandtumorsuppressorinintrahepaticcholangiocarcinoma
AT changzhenshang identificationoffoxp1asafavorableprognosticbiomarkerandtumorsuppressorinintrahepaticcholangiocarcinoma
AT zhaohuitang identificationoffoxp1asafavorableprognosticbiomarkerandtumorsuppressorinintrahepaticcholangiocarcinoma