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.
Highlights
Malignant peripheral nerve sheath tumor (MPNST) is a subtype of soft tissue sarcoma of ectomesenchyme origin, arising from peripheral nerve branches or sheaths of peripheral nerve fibers [1, 2]
We demonstrated the percentage of each gene mutation in these 10 samples and mutation rate per MB in each sample, which indicated the landscape of genetic aberrations of MPNST (Figures 1B & 1C)
There were genes mutations of TBX2, CHK2 and p53 in our samples, so it suggests that genetic mutations of TBX2CHK2-p53 pathway are important factors and may cause the aberrant expression of corresponding proteins
Summary
Malignant peripheral nerve sheath tumor (MPNST) is a subtype of soft tissue sarcoma of ectomesenchyme origin, arising from peripheral nerve branches or sheaths of peripheral nerve fibers [1, 2]. The overall incidence of MPNST in the general population is 1/100000 and it accounts for approximately 5–10% of all soft tissue sarcomas [1,2,3,4,5,6,7]. They occur either sporadically, in association with neurofibromatosis type 1 (NF1), or subsequent to radiation therapy [8,9,10]. Methods: Genetic aberrations of TBX2, CHK2 and p53 were detected by generation sequencing (NGS) in 10 MPNST samples. TBX2 and CHK2 might be useful markers for MPNST
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