Expression of FOXP1 and Colorectal Cancer Prognosis

被引:20
作者
De Smedt, Linde [1 ]
Palmans, Sofie [1 ]
Govaere, Olivier [1 ]
Moisse, Matthieu [2 ,3 ]
Boeckx, Bram [2 ,3 ]
De Hertogh, Gert [2 ,3 ]
Prenen, Hans
Van Cutsem, Erik [4 ]
Tejpar, Sabine [4 ]
Tousseyn, Thomas [1 ]
Sagaert, Xavier [1 ]
机构
[1] Katholieke Univ Leuven, Translat Cell & Tissue Res Unit, Dept Imaging & Pathol, Leuven, Belgium
[2] Vlaams Inst Voor Biotechnol VIB, Vesalius Res Ctr, Leuven, Belgium
[3] KU Leuven Belgium, Lab Translat Genet, Dept Oncol, Louvain, Belgium
[4] Univ Hosp Leuven, Digest Oncol Unit, Dept Oncol, Louvain, Belgium
来源
LABMEDICINE | 2015年 / 46卷 / 04期
关键词
immunohistochemistry; tumor markers; cancer research; colorectal cancer; FOXP1; prognosis; FORKHEAD TRANSCRIPTION FACTOR; B-CELL LYMPHOMA; PHYSICAL-ACTIVITY; POOR-PROGNOSIS; SURVIVAL; GENES; ISOFORMS; RECEPTOR; SUBSET; DIET;
D O I
10.1309/LM7IHV2NJI1PHMXC
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
100118 [医学信息学]; 100208 [临床检验诊断学];
摘要
Background: Forkhead box gene P1 (FOXP1) has proven to be a valuable prognostic biomarker in lymphomas, but little is known about this gene in colorectal cancer (CRC). Objectives: To investigate the expression of FOXP1 in CRC and its potential associations with outcome in CRC. Methods: We studied the expression pattern of FOXP1 retrospectively via immunohistochemistry in a series of 165 - CRC cases. Fluorescent in situ hybridization and RNA sequencing on FOXP1 knockdown cell lines were performed to investigate the mechanism of action and target genes of FOXP1. Results: Complete loss of nuclear FOXP1 expression was observed in 11.5% of the subjects. A total of 70.9% of subjects showed a heterogeneous FOXP1 expression pattern, and 17.6% of them had high FOXP1 expression. Impaired expression of FOXP1 was significantly correlated with reduced survival rates by multivariate analysis (P = .004). We found no chromosomal aberrations involving FOXP1 in individuals with FOXP1 negativity via immunohistochemical testing. RNA sequencing revealed that genes involved in inflammation and cell proliferation were differentially expressed after FOXP1 knockdown. Conclusions: In our case series, loss of FOXP1 was associated with reduced survival rates in CRC tissue. Also, FOXP1 affects proliferation and inflammatory reaction in colorectal neoplasia.
引用
收藏
页码:299 / 311
页数:13
相关论文
共 45 条
[1]
Banham AH, 2005, CLIN CANCER RES, V11, P1065
[2]
Banham AH, 2001, CANCER RES, V61, P8820
[3]
Expression of the forkhead transcription factor FOXP1 is associated both with hypoxia inducible factors (HIFs) and the androgen receptor in prostate cancer but is not directly regulated by androgens or hypoxia [J].
Banham, Alison H. ;
Boddy, Jane ;
Launchbury, Rosalind ;
Han, Cheng ;
Turley, Helen ;
Malone, Peter R. ;
Harris, Adrian L. ;
Fox, Stephen B. .
PROSTATE, 2007, 67 (10) :1091-1098
[4]
Strong expression of FOXP1 identifies a distinct subset of diffuse large B-cell lymphoma (DLBCL) patients with poor outcome [J].
Barrans, SL ;
Fenton, JAL ;
Banham, A ;
Owen, RG ;
Jack, AS .
BLOOD, 2004, 104 (09) :2933-2935
[5]
Potentially oncogenic B-cell activation-induced smaller isoforms of FOXP1 are highly expressed in the activated B cell-like subtype of DLBCL [J].
Brown, Philip J. ;
Ashe, Sally L. ;
Leich, Ellen ;
Burek, Christof ;
Barrans, Sharon ;
Fenton, James A. ;
Jack, Andrew S. ;
Pulford, Karen ;
Rosenwald, Andreas ;
Banham, Alison H. .
BLOOD, 2008, 111 (05) :2816-2824
[6]
Preferential Expression of Truncated Isoforms of FOXP1 in Primary Central Nervous System Lymphoma [J].
Courts, Cornelius ;
Brunn, Anna ;
Montesinos-Rongen, Manuel ;
Siemer, Doerte ;
Hans, Volkmar ;
Paulus, Werner ;
Wiestler, Otmar D. ;
Kueppers, Ralf ;
Siebert, Reiner ;
Deckert, Martina .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2009, 68 (09) :972-976
[7]
Hox repertoires for motor neuron diversity and connectivity gated by a single accessory factor, FoxP1 [J].
Dasen, Jeremy S. ;
De Camilli, Alessandro ;
Wang, Bin ;
Tucker, Philip W. ;
Jessell, Thomas M. .
CELL, 2008, 134 (02) :304-316
[8]
Genetic predisposition to colorectal cancer [J].
de la Chapelle, A .
NATURE REVIEWS CANCER, 2004, 4 (10) :769-780
[9]
Fang J, Am J Clin PathoL, P230