Localized- and advanced-stage follicular lymphomas differ in their gene expression profiles

Area of Science:

• Hematology
• Oncology
• Molecular Biology

Background:

• Follicular lymphoma (FL) genetic background is understood for advanced stages (III/IV), often with t(14;18).
• Localized-stage FL (I/II) has limited genetic information, with t(14;18) detected in only ~50% of cases.
• Risk stratification in FL typically relies on clinicogenetic models like m7FLIPI for advanced stages.

Purpose of the Study:

• To investigate the genetic differences between localized-stage and advanced-stage follicular lymphoma.
• To identify gene expression (GE) signatures that can distinguish between these two clinical stages of FL.
• To assess the prognostic value of these identified GE signatures in FL patient cohorts.

Main Methods:

• Comparative analysis of patient cohorts from German Low-Grade Lymphoma Study Group phase 3 trials.
• Targeted gene expression (GE) profiling of 184 genes using nCounter technology.
• Analysis of 110 localized-stage and 556 advanced-stage FL patients using penalized Cox and logistic regression.

Main Results:

• Robust GE signatures were identified that effectively discriminate between localized-stage and advanced-stage FL (AUC = 0.98).
• A subset of localized-stage FL samples with an 'advanced-stage signature' showed significantly inferior failure-free survival (HR=7.1).
• A subset of advanced-stage FL samples with a 'localized-stage signature' exhibited prolonged failure-free survival (HR=2.3) and overall survival (HR=3.4).

Conclusions:

• Distinct biological differences exist between localized-stage and advanced-stage follicular lymphoma.
• Identified GE signatures can differentiate FL stages and predict patient outcomes.
• These findings may explain the superior prognosis observed in patients with localized-stage FL.