Limits...
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

The associations of the ratio of M2/M1 macrophage in tumour centre or at tumour edge with nodal status and overall survival. (A) The ratio of M2/M1 macrophage is significantly higher in EAC N1-3 compared with that in EAC N0. (B) The ratio of M2/M1 macrophage in tumour centre or at tumour edge is related to lymph node metastasis (X2 test). (C) Kaplan–Meier overall survival curves of 31 EAC patients stratified by the ratio of M2/M1 macrophage in tumour centre and at tumour edge based on the median number.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4559839&req=5

fig2: The associations of the ratio of M2/M1 macrophage in tumour centre or at tumour edge with nodal status and overall survival. (A) The ratio of M2/M1 macrophage is significantly higher in EAC N1-3 compared with that in EAC N0. (B) The ratio of M2/M1 macrophage in tumour centre or at tumour edge is related to lymph node metastasis (X2 test). (C) Kaplan–Meier overall survival curves of 31 EAC patients stratified by the ratio of M2/M1 macrophage in tumour centre and at tumour edge based on the median number.

Mentions: In this study, the ratio of M2/M1 macrophage was significantly increased in EACs with nodal spread independent of locations, either in tumour centre (from 0.455±0.051 to 1.417±0.325) or at tumour edge (from 0.5918±0.155 to 2.404±0.635; Figure 2A). The median value of M2/M1 ratio was 0.6 at tumour edge and 0.47 in tumour centre. Subsequently, the data indicated that a higher M2/M1 ratio at tumour edge (>0.6) or in tumour centre (>0.47) was strongly associated with lymph node metastasis (Figure 2B). Furthermore, a higher M2/M1 ratio was associated with poor prognosis of EAC patients (Figure 2C), also in a manner of independent of locations of macrophage in tumour. Notably, in our cohort, lymph node metastasis was related to poor prognosis (Supplementary Figure 4), which was in agreement with previous studies (Bollschweiler et al, 2006; Wijnhoven et al, 2007).


Macrophage subtype predicts lymph node metastasis in oesophageal adenocarcinoma and promotes cancer cell invasion in vitro
The associations of the ratio of M2/M1 macrophage in tumour centre or at tumour edge with nodal status and overall survival. (A) The ratio of M2/M1 macrophage is significantly higher in EAC N1-3 compared with that in EAC N0. (B) The ratio of M2/M1 macrophage in tumour centre or at tumour edge is related to lymph node metastasis (X2 test). (C) Kaplan–Meier overall survival curves of 31 EAC patients stratified by the ratio of M2/M1 macrophage 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

fig2: The associations of the ratio of M2/M1 macrophage in tumour centre or at tumour edge with nodal status and overall survival. (A) The ratio of M2/M1 macrophage is significantly higher in EAC N1-3 compared with that in EAC N0. (B) The ratio of M2/M1 macrophage in tumour centre or at tumour edge is related to lymph node metastasis (X2 test). (C) Kaplan–Meier overall survival curves of 31 EAC patients stratified by the ratio of M2/M1 macrophage in tumour centre and at tumour edge based on the median number.
Mentions: In this study, the ratio of M2/M1 macrophage was significantly increased in EACs with nodal spread independent of locations, either in tumour centre (from 0.455±0.051 to 1.417±0.325) or at tumour edge (from 0.5918±0.155 to 2.404±0.635; Figure 2A). The median value of M2/M1 ratio was 0.6 at tumour edge and 0.47 in tumour centre. Subsequently, the data indicated that a higher M2/M1 ratio at tumour edge (>0.6) or in tumour centre (>0.47) was strongly associated with lymph node metastasis (Figure 2B). Furthermore, a higher M2/M1 ratio was associated with poor prognosis of EAC patients (Figure 2C), also in a manner of independent of locations of macrophage in tumour. Notably, in our cohort, lymph node metastasis was related to poor prognosis (Supplementary Figure 4), which was in agreement with previous studies (Bollschweiler et al, 2006; Wijnhoven et al, 2007).

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