Open Access

JAK3/STAT3 oncogenic pathway and PRDM1 expression stratify clinicopathologic features of extranodal NK/T‑cell lymphoma, nasal type

  • Authors:
    • Jumei Liu
    • Li Liang
    • Dong Li
    • Lin Nong
    • Yalin Zheng
    • Sixia Huang
    • Bo Zhang
    • Ting Li
  • View Affiliations

  • Published online on: April 12, 2019     https://doi.org/10.3892/or.2019.7112
  • Pages: 3219-3232
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The inactivation of tumor suppressor gene positive regulatory domain containing I (PRDM1) and activation of signal transducer and activator of transcription 3 (STAT3) have been detected in the majority of extranodal NK/T‑cell lymphoma, nasal type (EN‑NK/T‑NT) cases. In the present study, their association with and effects on the clinicopathologic features of EN‑NK/T‑NT are described. PRDM1 was revealed to be expressed in 19 out of 58 patients (32.8%) with EN‑NK/T‑NT, and phosphorylated STAT3 was overexpressed in 42 out of 58 (72.4%). Oncogenic pathways were investigated by NanoString encounter technology in 5 PRDM1(+) and 5 PRDM1(‑) EN‑NK/T‑NT specimens. Multiple oncogenic pathways involved in cell apoptosis, cellcycle (CC) and angiogenesis were discriminately activated in EN‑NK/T‑NT cases, and in PRDM1(+) cases in particular. The sustained activation of the Janus kinase 3 (JAK)/STAT3 pathway was more pronounced. In addition, missense mutations in the SRC homology 2 domain of STAT3 were detected in 7 out of 37 EN‑NK/T‑NT cases (18.92%), and the acquired mutation was related to the activation of the JAK3/STAT3 pathway. The downregulation of PRDM1 and upregulation of phospho‑STAT3 (Tyr705) were associated with angiocentric infiltration of EN‑NK/T‑NT (P=0.039). Notably, the prognosis of patients in the PRDM1(+)/STAT3 [mutated (mut‑)] group was considerably improved than that of patients in the STAT3(mut+)/PRDM(‑) group (P=0.037). In addition, the inhibition of NK/T cell lymphoma cell lines by Stattic and tofacitinib could suppress cell proliferation by inducing cell apoptosis or arresting the CC. The present results revealed that the JAK3/STAT3 oncogenic pathway and PRDM1 expression could stratify clinicopathologic features of EN‑NK/T‑NT. The inhibition of the JAK3/STAT3 pathway may serve as a treatment option for EN‑NK/T‑NT.

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June 2019
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Copy and paste a formatted citation
APA
Liu, J., Liang, L., Li, D., Nong, L., Zheng, Y., Huang, S. ... Li, T. (2019). JAK3/STAT3 oncogenic pathway and PRDM1 expression stratify clinicopathologic features of extranodal NK/T‑cell lymphoma, nasal type. Oncology Reports, 41, 3219-3232. https://doi.org/10.3892/or.2019.7112
MLA
Liu, J., Liang, L., Li, D., Nong, L., Zheng, Y., Huang, S., Zhang, B., Li, T."JAK3/STAT3 oncogenic pathway and PRDM1 expression stratify clinicopathologic features of extranodal NK/T‑cell lymphoma, nasal type". Oncology Reports 41.6 (2019): 3219-3232.
Chicago
Liu, J., Liang, L., Li, D., Nong, L., Zheng, Y., Huang, S., Zhang, B., Li, T."JAK3/STAT3 oncogenic pathway and PRDM1 expression stratify clinicopathologic features of extranodal NK/T‑cell lymphoma, nasal type". Oncology Reports 41, no. 6 (2019): 3219-3232. https://doi.org/10.3892/or.2019.7112