A research team identified possible prognostic markers in extranodal natural killer T-cell lymphoma (ENKTL) through an analysis of gene expression profiling data, with evidence pointing to the importance of expression of early growth response protein 1 (EGR1). The researchers recently presented the findings of this analysis in the journal Scientific Reports.

They explained in their report that prognosis in ENKTL has shown improvements with newer therapies, but relapsed/refractory cases continue to be at high risk of poor outcomes. The research team undertook an investigation of molecular markers in ENKTL that may aid in prognosis with this condition.

Gene expression was assessed using NanoString nCounter Analysis (NanoString Technologies, Seattle, WA) with RNA obtained from tumor samples of 43 patients with ENKTL. This analysis included a total of 133 target genes and 4 housekeeping genes. Western blot was also performed for analyses of proteins, and apoptosis assays were also conducted. Survival outcomes were evaluated with respect to gene expression profiling analysis.


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Slightly over half (53.5%) of patients in this analysis had intermediate- or high-risk ENKTL, based on the prognostic index for natural killer cell lymphoma (PINK). Most patients (74.4%) had nasal-type ENKTL, and most patients (79.1%) were at or below 60 years of age. The Eastern Cooperative Oncology Group performance status was 0 or 1 in 81.4% of patients.

At a median follow-up of 15.9 months, the median overall survival was 16.1 months (95% CI, 13.0-69.8). Approximately two-thirds (67.4%) of patients had disease progression after primary treatment, and the 3-year overall survival rate was reportedly 47%.

Upregulation of EGR1 appeared associated with localized tumors and with a low risk based on the PINK and PINK-Epstein-Barr virus. Additionally, there were 4 genes related to EGR1 expression that appeared to be linked to survival: increased expression of CD59, GAS1, CXCR7, RAMP3 genes was seen with better survival outcomes. In vitro analyses revealed that expression of these genes seemed to be significantly reduced when EGR1 gene expression was inhibited. Silencing of CD59, GAS1, CXCR7, RAMP3, and EGR1 genes also was associated with reduced apoptosis in the presence of doxorubicin or radiation, as determined by in vitro analyses.

“In summary, the results indicate that EGR1 may represent a useful prognostic marker in ENKTL,” the researchers concluded in their report. They also suggested that reintroducing the EGR1 gene might serve as a therapeutic intervention.

Reference

Lee JY, Kim JH, Bang H, et al. EGR1 as a potential marker of prognosis in extranodal NK/T‑cell lymphoma. Sci Rep. 2021;11(1):10342. doi:10.1038/s41598-021-89754-8