PLA2G2A overexpression is associated with poor therapeutic response and inferior outcome in rectal cancer patients receiving neoadjuvant concurrent chemoradiotherapy.
OBJECTIVE
The aim of this study was to investigate the prognostic impact of group IIA phospholipase A2 (PLA2G2A) expression and its role in predicting the response to neoadjuvant concurrent cheomoradiotherapy (CCRT) in rectal cancer.


RESULTS
Through analysing a public transcriptome of rectal cancers, the PLA2G2A gene was identified as a significant predictor for CCRT response. We validated the expression of PLA2G2A using immunohistochemistry in the pretreatment tumour specimens from 172 patients with rectal cancer. The results were correlated with clinicopathological features, tumour regression grade, overall survival (OS), disease-free survival (DFS) and local recurrence-free survival (LRFS). High expression of PLA2G2A was associated with advanced pretreatment tumour status (P = 0.001), advanced pretreatment nodal status (P = 0.010), advanced post-treatment tumour status (P = 0.002) and lower tumour regression grade (P = 0.006). Furthermore, PLA2G2A expression was correlated negatively with gamma H2A histone family, member X (γ-H2AX) expression (P < 0.001, r = -0.580). More importantly, high expression of PLA2G2A emerged as an adverse prognostic factor for OS (P = 0.0190), DFS (P < 0.0001) and LRFS (P < 0.0001). In multivariate analysis, it remained independently prognostic for shorter DFS (P = 0.014) and LRFS (P = 0.012).


CONCLUSIONS
High expression of PLA2G2A was associated with poor therapeutic response and worse survival in patients with rectal cancer receiving neoadjuvant CCRT, justifying PLA2G2A as an important marker to predict CCRT response and outcome.
Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan.|Institute of Biomedical Science, National Sun Yat-sen University, Kaohsiung, Taiwan.
Hong-Lin
HL
He
Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Ying-En
YE
Lee
Institute of Biomedical Science, National Sun Yat-sen University, Kaohsiung, Taiwan.
Yow-Ling
YL
Shiue
Department of Radiation Oncology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan.
Sung-Wei
SW
Lee
Department of Radiation Oncology, Chi-Mei Medical Center, Tainan, Taiwan.
Li-Ching
LC
Lin
Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan.
Tzu-Ju
TJ
Chen
Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan.
Ting-Feng
TF
Wu
Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan.|Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan.|Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
Chien-Feng
CF
Li
D000368:Aged; D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D005260:Female; D054501:Group II Phospholipases A2 / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020360:Neoadjuvant Therapy; D011379:Prognosis; D012004:Rectal Neoplasms / Q000378:metabolism* / Q000628:therapy*; D016896:Treatment Outcome
D006657:Histones; D054501:Group II Phospholipases A2; C516287:PLA2G2A protein, human
CCRT; PLA2G2A; chemoradiotherapy; rectal cancer