Chao  Zhang,Fangyuan  Chang,Hongji  Dai,Jilong Yang,Ting   Li,Xiaoling  Du,
Aberrations of TBX2-CHK2-p53 Signaling Pathway and its Role in Malignant Peripheral Nerve Sheath Tumors
Journal of Surgical Oncology
2020
2674-3000
http://dx.doi.org/10.31487/j.JSO.2020.02.09
https://www.sciencerepository.org/aberrations-of-tbx2-chk2-p53-signaling-pathway_JSO-2020-2-109 
Abstract: 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.
Keywords: Malignant peripheral nerve sheath, tumor, next generation sequencing, TBX2, CHK2, proliferation