Tumor Mutation Burden Prediction Model in Egyptian Breast Cancer patients based on Next Generation Sequencing.

Auhood Nassar,Amira Youssef,Tamer Manie,Abdel-Rhaman Zekri,Ahmed Lymona,Mai Lotfy,Mina Youssef,Iman Farahat,Marwa Mohanad

doi:10.31557/apjcp.2021.22.7.2053

Abstract

Objectives:This study aimed to identify the tumor mutation burden (TMB) value in Egyptian breast cancer (BC) patients. Moreover, to find the best TMB prediction model based on the expression of estrogen (ER), progesterone (PR), human epidermal growth factor receptor 2 (HER-2), and proliferation index Ki-67. Methods:The Ion AmpliSeq Comprehensive Cancer Panel was used to determine TMB value of 58 Egyptian BC tumor tissues. Different machine learning models were used to select the optimal classification model for prediction of TMB level according to patient’s receptor status. Results:The measured TMB value was between 0 and 8.12/Mb. Positive expression of ER and PR was significantly associated with TMB ≤ 1.25 [(OR =0.35, 95% CI: 0.04–2.98), (OR = 0.17, 95% CI= 0.02-0.44)] respectively. Ki-67 expression positive was significantly associated with TMB >1.25 than those who were Ki-67 expression negative (OR = 9.33, 95% CI= 2.07-42.18). However, no significant differences were observed between HER2 positive and HER2 negative groups. The optimized logistic regression model was TMB = -27.5 -1.82 ER – 0.73 PR + 0.826 HER2 + 2.08 Ki-67. Conclusion:Our findings revealed that TMB value can be predicted based on the expression level of ER, PR, HER-2, and Ki-67.

Highlights

breast cancer (BC) is a heterogeneous disease comprises different subtypes classified according to the expression of ER, PR, human epidermal growth factor receptor 2 (HER-2), and Ki-67 [Caswell and Swanton, 2017; Osako et al, 2017)
We found that ER and PR positivity associated significantly with lower tumor mutation burden (TMB) quartile while, higher TMB quartile was significantly observed in patients with positive Ki-67 expression and TNBC
BC was classified based on the presence of the ER, PR, HER-2, and Ki-67, the routinely available markers in each BC specimen (Osako et al, 2017)

Summary

Introduction

BC is a heterogeneous disease comprises different subtypes classified according to the expression of ER, PR, HER-2, and Ki-67 [Caswell and Swanton, 2017; Osako et al, 2017). Several studies revealed the role of the immune system in cancer; including cancer immunoediting process which eliminates immunogenic tumor cells by the host immune system (Criscitiello and Curigliano, 2015). As a genetic disease, results in accumulation of somatic mutations in the DNA of the affected cells. Some somatic mutations can give rise to neoantigens that are recognized and targeted by the immune system. Immunogenic neoantigens affect the ability of T cells to identify and kill tumor cell, but mutations in immunologically relevant genes can do, for example; mutations in JAK1, JAK2, B2M, and STK11genes (Skoulidis et al, 2018)

Objectives

Results

Conclusion