Exploring the Potential of Enhanced Prognostic Performance of NCCN-IPI in Diffuse Large B-Cell Lymphoma by Integrating Tumor Microenvironment Markers: Stromal FOXC1 and Tumor pERK1/2 Expression
  • Kim, Ji-Ye
  • Kahttana, Ibadullah
  • Yoon, Hyonok
  • Chang, Sunhee
  • Yoon, Sun Och
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초록

Background: FOXC1 and ERK1-2 are proteins implicated in aggressive biological behavior of various malignancies including lymphomas. Material and Methods: We investigate the additive prognostic value of stromal FOXC1 expression and tumor phosphorylated ERK1-2 (pERK1-2) expression to the established National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI), in 92 diffuse large B-cell lymphoma (DLBCL) cases. Multidimensional analysis using statistics and machine learning (ML) models assessed prognostic value of established clinicopathologic variables with stromal FOXC1 and tumor pERK1-2 expressions. Results: Both high FOXC1 stroma group and high pERK1-2 tumor group were significantly associated with shorter progression-free survival (PFS) and overall survival (OS) compared with low group (p = 0.015, 0.034 and p = 0.025, 0.025 each respectively). In multivariable analysis, high FOXC1 stromal expression was an independent prognostic factor of OS (p = 0.037). The addition of stromal FOXC1 and tumor pERK1-2 to the NCCN-IPI score significantly improved prediction of time to death compared with NCCN-IPI score alone (Harrell's C-index = 0.801 vs. 0.764; p = 0.030). ML models reconfirmed the addition of stromal FOXC1 expression and tumor pERK1-2 to NCCN-IPI score had the highest C-index (0.952) among combinations. Stromal FOXC1 and tumor pERK1-2 were determinants of DLBCL prognosis, whose addition significantly improved prognostic performance of the NCCN-IPI.

키워드

Diffuse Large B-cell LymphomaFOXC1Machine Learning ModelspERK1-2Prognostic MarkersTumor MicroenvironmentVARIABLE SELECTIONSURVIVALPROTEINCONTRIBUTESSIGNATURESMYC
제목
Exploring the Potential of Enhanced Prognostic Performance of NCCN-IPI in Diffuse Large B-Cell Lymphoma by Integrating Tumor Microenvironment Markers: Stromal FOXC1 and Tumor pERK1/2 Expression
저자
Kim, Ji-YeKahttana, IbadullahYoon, HyonokChang, SunheeYoon, Sun Och
DOI
10.1002/cam4.70305
발행일
2024-10
유형
Article
저널명
Cancer Medicine
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19