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Macrophage subtype predicts lymph node metastasis in oesophageal adenocarcinoma and promotes cancer cell invasion in vitro

View Article: PubMed Central - PubMed

ABSTRACT

Background:: Currently, there is a lack of ideal biomarkers for predicting nodal status in preoperative stage of oesophageal adenocarcinoma (EAC) to aid optimising therapeutic options. We studied the potential of applying subtype macrophages to predict lymph node metastasis and prognosis in EAC.

Material and methods:: Fifty-three EAC resection specimens were immunostained with CD68, CD40 (M1), and CD163 (M2). Lymphatic vessel density (LVD) was estimated with the staining of D2-40. Subsequently, we tested if M2d macrophage could promote EAC cell migration and invasion.

Results:: In EAC without neoadjuvant treatment, an increase in M2-like macrophage was associated with poor patient survival, independent of the locations of macrophages in tumour. The M2/M1 ratio that represented the balance between M2- and M1-like macrophages was significantly higher in nodal-positive EACs than that in nodal-negative EACs, and inversely correlated with patient overall survival. The M2/M1 ratio was not related to LVD. EAC cell polarised THP1 cell into M2d-like macrophage, which promoted EAC cell migration and invasion. Neoadjuvant therapy appeared to diminish the correlation between the M2/M1 ratio and survival.

Conclusions:: The ratio of M2/M1 macrophage may serve as a sensitive marker to predict lymph node metastasis and poor prognosis in EAC without neoadjuvant therapy. M2d macrophage may have important roles in EAC metastasis.

No MeSH data available.


Related in: MedlinePlus

Lymphatic vessel density (LVD) in tumour centre or at tumour edge is not associated with the ratio of M2/M1 macrophage or patient overall survival. (A) Correlation of LVD in tumour centre or at tumour edge with the ratio of M2/M1 macrophage (Pearson's test). (B) Kaplan–Meier overall survival curves of 31 EAC patients stratified by LVD in tumour centre and at tumour edge based on the median number.
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fig3: Lymphatic vessel density (LVD) in tumour centre or at tumour edge is not associated with the ratio of M2/M1 macrophage or patient overall survival. (A) Correlation of LVD in tumour centre or at tumour edge with the ratio of M2/M1 macrophage (Pearson's test). (B) Kaplan–Meier overall survival curves of 31 EAC patients stratified by LVD in tumour centre and at tumour edge based on the median number.

Mentions: To understand whether LVD correlated with lymph node metastasis, the ratio of M2/M1 or patient survival in our study, D2-40 immunohistochemistry was performed (Supplementary Figure 5A). The median LVD was 4.8 lymphatic vessels per high-power field in tumour centre and 11.8 lymphatic vessels at tumour edge. LVD in tumour centre or at tumour edge seemed not to associate with the ratio of M2/M1 macrophage or patient OS (Figure 3A and B). LVD in tumour centre was associated with nodal spread (Supplementary Figure 5B). But we did not observe the association between LVD at tumour edge and nodal spread (Supplementary Figure 5B). The data implied that LVD may not be an ideal predictor for lymph node metastasis or prognosis in EAC.


Macrophage subtype predicts lymph node metastasis in oesophageal adenocarcinoma and promotes cancer cell invasion in vitro
Lymphatic vessel density (LVD) in tumour centre or at tumour edge is not associated with the ratio of M2/M1 macrophage or patient overall survival. (A) Correlation of LVD in tumour centre or at tumour edge with the ratio of M2/M1 macrophage (Pearson's test). (B) Kaplan–Meier overall survival curves of 31 EAC patients stratified by LVD in tumour centre and at tumour edge based on the median number.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4559839&req=5

fig3: Lymphatic vessel density (LVD) in tumour centre or at tumour edge is not associated with the ratio of M2/M1 macrophage or patient overall survival. (A) Correlation of LVD in tumour centre or at tumour edge with the ratio of M2/M1 macrophage (Pearson's test). (B) Kaplan–Meier overall survival curves of 31 EAC patients stratified by LVD in tumour centre and at tumour edge based on the median number.
Mentions: To understand whether LVD correlated with lymph node metastasis, the ratio of M2/M1 or patient survival in our study, D2-40 immunohistochemistry was performed (Supplementary Figure 5A). The median LVD was 4.8 lymphatic vessels per high-power field in tumour centre and 11.8 lymphatic vessels at tumour edge. LVD in tumour centre or at tumour edge seemed not to associate with the ratio of M2/M1 macrophage or patient OS (Figure 3A and B). LVD in tumour centre was associated with nodal spread (Supplementary Figure 5B). But we did not observe the association between LVD at tumour edge and nodal spread (Supplementary Figure 5B). The data implied that LVD may not be an ideal predictor for lymph node metastasis or prognosis in EAC.

View Article: PubMed Central - PubMed

ABSTRACT

Background:: Currently, there is a lack of ideal biomarkers for predicting nodal status in preoperative stage of oesophageal adenocarcinoma (EAC) to aid optimising therapeutic options. We studied the potential of applying subtype macrophages to predict lymph node metastasis and prognosis in EAC.

Material and methods:: Fifty-three EAC resection specimens were immunostained with CD68, CD40 (M1), and CD163 (M2). Lymphatic vessel density (LVD) was estimated with the staining of D2-40. Subsequently, we tested if M2d macrophage could promote EAC cell migration and invasion.

Results:: In EAC without neoadjuvant treatment, an increase in M2-like macrophage was associated with poor patient survival, independent of the locations of macrophages in tumour. The M2/M1 ratio that represented the balance between M2- and M1-like macrophages was significantly higher in nodal-positive EACs than that in nodal-negative EACs, and inversely correlated with patient overall survival. The M2/M1 ratio was not related to LVD. EAC cell polarised THP1 cell into M2d-like macrophage, which promoted EAC cell migration and invasion. Neoadjuvant therapy appeared to diminish the correlation between the M2/M1 ratio and survival.

Conclusions:: The ratio of M2/M1 macrophage may serve as a sensitive marker to predict lymph node metastasis and poor prognosis in EAC without neoadjuvant therapy. M2d macrophage may have important roles in EAC metastasis.

No MeSH data available.


Related in: MedlinePlus