A Comprehensive Search of Non-Canonical Proteins in Non-Small Cell Lung Cancer and Their Impact on the Immune Response

Authors

Ehsan Irajizad
Johannes F Fahrmann
James P Long
Jody Vykoukal
Makoto Kobayashi
Michela Capello
Chuan-Yih Yu
Yining Cai
Fu Chung Hsiao
Nikul Patel
Soyoung Park
Qian Peng
Jennifer B Dennison
Taketo Kato
Mei Chee Tai
Ayumu Taguchi
Humam Kadara
Ignacio I Wistuba
Hiroyuki Katayama
Kim-Anh Do
Samir M Hanash
Edwin J Ostrin

Publication Date

8-11-2022

Journal

International Journal of Molecular Sciences

DOI

10.3390/ijms23168933

PMID

36012199

PMCID

PMC9409146

PubMedCentral® Posted Date

8-11-2022

PubMedCentral® Full Text Version

Post-print

Abstract

There is substantial interest in mining neoantigens for cancer applications. Non-canonical proteins resulting from frameshift mutations have been identified as neoantigens in cancer. We investigated the landscape of non-canonical proteins in non-small cell lung cancer (NSCLC) and their induced immune response in the form of autoantibodies. A database of cryptoproteins was computationally constructed and comprised all alternate open reading frames (altORFs) and ORFs identified in pseudogenes, noncoding RNAs, and untranslated regions of mRNAs that did not align with known canonical proteins. Proteomic profiles of seventeen lung adenocarcinoma (LUAD) cell lines were searched to evaluate the occurrence of cryptoproteins. To assess the immunogenicity, immunoglobulin (Ig)-bound cryptoproteins in plasmas were profiled by mass spectrometry. The specimen set consisted of plasmas from 30 newly diagnosed NSCLC cases, pre-diagnostic plasmas from 51 NSCLC cases, and 102 control plasmas. An analysis of LUAD cell lines identified 420 cryptoproteins. Plasma Ig-bound analyses revealed 90 cryptoproteins uniquely found in cases and 14 cryptoproteins that had a fold-change >2 compared to controls. In pre-diagnostic samples, 17 Ig-bound cryptoproteins yielded an odds ratio ≥2. Eight Ig-bound cryptoproteins were elevated in both pre-diagnostic and newly diagnosed cases compared to controls. Cryptoproteins represent a class of neoantigens that induce an autoantibody response in NSCLC.

Keywords

Adenocarcinoma of Lung, Carcinoma, Non-Small-Cell Lung, Humans, Immunity, Lung Neoplasms, Proteins, Proteomics, noncanonical open reading frames, altORFs, neoantigens, autoantibodies, NSCLC

Published Open-Access

yes

Recommended Citation

Irajizad, Ehsan; Fahrmann, Johannes F; Long, James P; et al., "A Comprehensive Search of Non-Canonical Proteins in Non-Small Cell Lung Cancer and Their Impact on the Immune Response" (2022). Faculty, Staff and Student Publications. 3009.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/3009