TY - JOUR
AR - JSO-2020-2-109
TI - Aberrations of TBX2-CHK2-p53 Signaling Pathway and its Role in Malignant Peripheral Nerve Sheath Tumors
AU - Chao , Zhang
AU - Fangyuan , Chang
AU - Hongji , Dai
AU - Jilong, Yang
AU - Ting ,  Li
AU - Xiaoling , Du
JO - Journal of Surgical Oncology
PY - 2020
DA - Wed 29, Apr 2020
SN - 2674-3000
DO - http://dx.doi.org/10.31487/j.JSO.2020.02.09
UR - https://www.sciencerepository.org/aberrations-of-tbx2-chk2-p53-signaling-pathway_JSO-2020-2-109 
KW - Malignant peripheral nerve sheath, tumor, next generation sequencing, TBX2, CHK2, proliferation
AB - Background and Objectives: The dismal outcome of malignant peripheral nerve sheath tumor (MPNST)
highlights the necessity of identifying new biomarkers and pathogenesis for this aggressive sarcoma.
Therefore, it is necessary to detect the aberrations of the TBX2-CHK2-p53 pathway and investigate its
biological role in MPNST.
Methods: Genetic aberrations of TBX2, CHK2 and p53 were detected by next generation sequencing
(NGS) in 10 MPNST samples. Protein expression of TBX2, CHK2, p53, Ki-67 and cyclin D1 were assessed
by immunohistochemistry (IHC) in 63 MPNST samples.
Results: Our present data demonstrated that there were gene mutations of TBX2, CHK2 and p53 in MPNST
samples. TBX2 expression was correlated with American Joint Committee on Cancer (AJCC) stage,
recurrence and metastasis. Correlation analysis found that TBX2 was positively correlated with CHK2
(p=0.045) and CHK2 was positively correlated with p53 (p=0.006). Furthermore, both CHK2 and p53 were
positively correlated with Ki-67 (p<0.05), which is related to tumor differentiation, metastasis and
prognosis. As for survival analyses, patients with high TBX2, CHK2 and p53 expression exhibited shorter
disease-free survival (DFS) and overall survival (OS), respectively (p<0.05) and TBX2 and CHK2 were
independent prognostic factors for MPNST patients (p<0.05).
Conclusion: There are genetic aberrations of the TBX2-CHK2-p53 signaling pathway in MPNST, which
might promote the progression of MPNST by increasing Ki-67 expression. Thus, TBX2 and CHK2 might
be useful markers for MPNST.