Tissue-based PEG10 expression as an exploratory biomarker associated with first-line R-CHOP treatment outcome in diffuse large B-cell lymphoma

Abstract

Aim: Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma, and 30-40% of patients develop primary resistance to first-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). This study evaluated tissue paternally expressed gene 10 (PEG10) expression as a biomarker of R-CHOP resistance.

Patients and methods: Retrospective observational cohort study utilizes formalin-fixed, paraffin-embedded lymph node tissues from 70 patients with DLBCL, 30 with indolent B-cell lymphoma, and 20 normal controls. PEG10 transcript expression was measured by quantitative real-time PCR and protein expression by immunohistochemistry. Associations with clinicopathological characteristics, prognostic indices, and treatment response were assessed using multivariable logistic regression.

Results: PEG10 transcript expression was higher in DLBCL than in indolent lymphoma and normal tissues. Elevated PEG10 expression was associated with advanced stage, poor ECOG performance status, higher International Prognostic Index scores, and R-CHOP resistance. Immunohistochemistry confirmed increased PEG10 protein expression in resistant tumors. PEG10 was not independently associated with resistance after adjustment (p = 0.163), whereas Ann Arbor stage remained independently associated (p = 0.042).

Conclusion: Tissue PEG10 overexpression is associated with adverse clinicopathological features and unfavorable R-CHOP response and may serve as an exploratory complementary tissue-based biomarker in DLBCL. These findings require validation in larger prospective multicenter cohorts before clinical implementation in practice.