Journal Article

Identification of FOXP1 as a favorable prognostic biomarker and tumor suppressor in intrahepatic cholangiocarcinoma

Tong, Huanjun, Shang, Changzhen, Hua, Yonglin, Ma, Xiaowu, Tang, Chenwei, Chen, Jialu, Wang, Bingkun, Wang, Qingbin, Yu, Xiaopeng, Tang, Zhaohui, Zhuang, Hongkai

2024

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Analysis / Antibodies / Apoptosis / Bile Duct Neoplasms / Bile ducts / Bile Ducts, Intrahepatic - pathology / Biological markers / Biomarkers / Biomarkers - metabolism / Biomedical and Life Sciences / Biomedicine / Cancer Research / Cancer therapies / Care and treatment / Cell Line, Tumor / Cell Proliferation / Cells / Cholangiocarcinoma / Comparative analysis / Diagnosis / Flow cytometry / Forkhead protein / Forkhead Transcription Factors - genetics / Forkhead Transcription Factors - metabolism / Foxp1 protein / Genetic aspects / Health Promotion and Disease Prevention / Humans / Immunohistochemistry / Intrahepatic cholangiocarcinoma / Liver cancer / Lymph nodes / Lymphatic Metastasis - pathology / Lymphatic system / Medical prognosis / Medical research / Medicine/Public Health / Metastases / Metastasis / Multivariate analysis / Oncology / Outcome prediction / Prognosis / Protein biomarker / Proteins / Repressor Proteins - metabolism / Risk factors / Surgical Oncology / Transcription Factors - metabolism / Tumor suppressor genes / Tumors