TY - JOUR
T1 - Detection of lymph node metastasis in colon cancer by ectopically expressed fibroblast markers FOXQ1 and THBS2
AU - Ali, Haytham
AU - AbdelMageed, Manar
AU - Olsson, Lina
AU - Lindmark, Gudrun
AU - Hammarström, Marie Louise
AU - Hammarström, Sten
AU - Sitohy, Basel
N1 - Copyright © 2023 Ali, AbdelMageed, Olsson, Lindmark, Hammarström, Hammarström and Sitohy.
PY - 2023/12/14
Y1 - 2023/12/14
N2 - INTRODUCTION: Approximately 25% of colon cancer (CC) patients having curative surgery will relapse. Therefore, it is crucial to identify patients with increased recurrence risk to offer them adjuvant chemotherapy. Three markers with prominent expression in fibroblasts: forkhead box Q1 (FOXQ1), matrix metalloproteinase-11 (MMP11), and thrombospondin-2 (THBS2), and the fibroblast expressed chemokine CXCL12 were selected for studies because of the critical role of fibroblasts in the microenvironment of the tumor.METHODS: The expression levels of the biomarkers were assessed in primary CC tumors, lymph nodes of CC patients and controls, and CC cell lines at mRNA and protein levels by real-time qRT-PCR and immunohistochemistry, respectively.RESULTS: FOXQ1, MMP11, and THBS2 mRNAs were expressed at significantly higher levels in primary tumors compared to normal colon (
P=0.002,
P<0.0001, and
P<0.0001, respectively). In contrast, CXCL12 mRNA levels were higher in normal colon tissue. FOXQ1, MMP11, and THBS2 levels were also expressed at significantly higher levels in metastasis-positive lymph nodes compared to both metastasis-negative- and control nodes
(P<0.0001
/P=0.002,
P<0.0001/P<0.0001, and
P<0.0001/P<0.0001, respectively). Immuno-morphometry revealed that 30-40% of the tumor cells expressed FOXQ1, MMP11, and THBS2. FOXQ1 and THBS2 were barely detected in normal colon epithelium (
P<0.0001), while MMP11 was expressed in normal colon epithelium at high levels.
DISCUSSION: We conclude that CC tumor cells show ectopic expression of FOXQ1 and THBS2 possibly making these tumor cells independent of fibroblast cell support. The high expression levels of these two biomarkers in metastatic lymph nodes suggest that they are potential indicators of patients at risk for recurrence.
AB - INTRODUCTION: Approximately 25% of colon cancer (CC) patients having curative surgery will relapse. Therefore, it is crucial to identify patients with increased recurrence risk to offer them adjuvant chemotherapy. Three markers with prominent expression in fibroblasts: forkhead box Q1 (FOXQ1), matrix metalloproteinase-11 (MMP11), and thrombospondin-2 (THBS2), and the fibroblast expressed chemokine CXCL12 were selected for studies because of the critical role of fibroblasts in the microenvironment of the tumor.METHODS: The expression levels of the biomarkers were assessed in primary CC tumors, lymph nodes of CC patients and controls, and CC cell lines at mRNA and protein levels by real-time qRT-PCR and immunohistochemistry, respectively.RESULTS: FOXQ1, MMP11, and THBS2 mRNAs were expressed at significantly higher levels in primary tumors compared to normal colon (
P=0.002,
P<0.0001, and
P<0.0001, respectively). In contrast, CXCL12 mRNA levels were higher in normal colon tissue. FOXQ1, MMP11, and THBS2 levels were also expressed at significantly higher levels in metastasis-positive lymph nodes compared to both metastasis-negative- and control nodes
(P<0.0001
/P=0.002,
P<0.0001/P<0.0001, and
P<0.0001/P<0.0001, respectively). Immuno-morphometry revealed that 30-40% of the tumor cells expressed FOXQ1, MMP11, and THBS2. FOXQ1 and THBS2 were barely detected in normal colon epithelium (
P<0.0001), while MMP11 was expressed in normal colon epithelium at high levels.
DISCUSSION: We conclude that CC tumor cells show ectopic expression of FOXQ1 and THBS2 possibly making these tumor cells independent of fibroblast cell support. The high expression levels of these two biomarkers in metastatic lymph nodes suggest that they are potential indicators of patients at risk for recurrence.
KW - CXCL12
KW - FOXQ1
KW - MMP11
KW - THBS2
KW - colon cancer
KW - fibroblasts
KW - immunohistochemistry
KW - qRT-PCR
UR - http://www.scopus.com/inward/record.url?scp=85180658536&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85180658536&partnerID=8YFLogxK
U2 - 10.3389/fonc.2023.1297324
DO - 10.3389/fonc.2023.1297324
M3 - Article
C2 - 38156105
AN - SCOPUS:85180658536
SN - 2234-943X
VL - 13
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 1297324
ER -