论文已发表
注册即可获取德孚的最新动态
IF 收录期刊
Authors Liu S, Ding G, Zhou Z, Feng C
Received 15 December 2017
Accepted for publication 1 March 2018
Published 9 April 2018 Volume 2018:11 Pages 2029—2036
DOI https://doi.org/10.2147/OTT.S159979
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Andrew Yee
Peer reviewer comments 3
Editor who approved publication: Dr Carlos Vigil Gonzales
Aim: Adrenocortical
carcinoma (ACC) is characterized by overexpressed CTNNB1 ,
which is reported to modulate immune exclusion. Cross talk between CTNNB1 and cancer immunity in
ACC remains unclear.
Materials and
methods: In silico reproduction of TCGA-ACC dataset (N =
92) and external validation using tissue samples were performed (N = 16).
Expression data of CTNNB1 , PD-1, and
PD-L1 were extracted in silico and tumor-infiltrating lymphocytes (TILs) were
profiled using code provided by Tumor IMmune Estimation Resource (TIMER).
In-house formalin-fixed paraffin-embedded ACC samples were processed using
immunohistochemical (IHC) staining for CTNNB1 , CD45, PD-1,
and PD-L1.
Results: Increased CTNNB1 expression was
significantly associated with worsened overall survival (OS) (P = 0.006). CD8+ cells were
significantly associated with better OS (P = 0.02).
Higher PD-L1 (P = 0.019), but not PD-1 expression
(P = 0.325), was associated
with better OS. CTNNB1 overexpression
was significantly associated with increased tumor purity (r = 0.356, P = 0.002) and fewer TILs (r = -0.833, P = 0.029), decreased
infiltrating CD8+ cells (P = 0.033), and increased
infiltrating B cells (P =
0.026). CTNNB1 expression was
negatively correlated with PD-L1 expression (r = -0.308, P = 0.006) but not with PD-1
expression (P = 0.067), which were
externally validated (P = 0.032 for
PD-L1 and P = 0.400 for PD-1). The Cox
regression model encompassing gender, B cells, CD8+ cells,
PD-L1, CTNNB1, and Ki-67 revealed that only Ki-67 overexpression remained
significantly associated with OS (P < 0.001),
while CTNNB1 showed marginal
significance (P = 0.06). CTNNB1 -overexpressed
patients were more likely to have cortisol excess (P =
0.003).
Conclusion: ACC with CTNNB1
overexpression is associated with poor prognosis and decreased immunity. Our
findings suggest that CTNNB1-targeting therapy may overcome immune exclusion in
ACC.
Keywords: adrenocortical
carcinoma, CTNNB1, tumor-infiltrating lymphocyte, PD-L1, prognosis