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

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

doi:10.3390/ijms23168933

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

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 DoSamir M. Hanash, Edwin J. Ostrin

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

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.

Original language	English (US)
Article number	8933
Journal	International journal of molecular sciences
Volume	23
Issue number	16
DOIs	https://doi.org/10.3390/ijms23168933
State	Published - Aug 2022

Keywords

altORFs
autoantibodies
neoantigens
noncanonical open reading frames
NSCLC

ASJC Scopus subject areas

Catalysis
Molecular Biology
Spectroscopy
Computer Science Applications
Physical and Theoretical Chemistry
Organic Chemistry
Inorganic Chemistry

MD Anderson CCSG core facilities

Biostatistics Resource Group
Clinical and Translational Research Center

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10.3390/ijms23168933

Cite this

Irajizad, E., Fahrmann, J. F., Long, J. P., Vykoukal, J., Kobayashi, M., Capello, M., Yu, C. Y., Cai, Y., Hsiao, F. C., Patel, N., Park, S., Peng, Q., Dennison, J. B., Kato, T., Tai, M. C., Taguchi, A., Kadara, H., Wistuba, I. I., Katayama, H., ... Ostrin, E. J. (2022). A Comprehensive Search of Non-Canonical Proteins in Non-Small Cell Lung Cancer and Their Impact on the Immune Response. International journal of molecular sciences, 23(16), Article 8933. https://doi.org/10.3390/ijms23168933

Irajizad, E , Fahrmann, JF , Long, JP , Vykoukal, J, Kobayashi, M, Capello, M, Yu, CY, Cai, Y , Hsiao, FC, Patel, N, Park, S, Peng, Q, Dennison, JB, Kato, T, Tai, MC, Taguchi, A, Kadara, H , Wistuba, II , Katayama, H , Do, KA , Hanash, SM & Ostrin, EJ 2022, 'A Comprehensive Search of Non-Canonical Proteins in Non-Small Cell Lung Cancer and Their Impact on the Immune Response', International journal of molecular sciences, vol. 23, no. 16, 8933. https://doi.org/10.3390/ijms23168933

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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.",

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AU - Vykoukal, Jody

AU - Kobayashi, Makoto

AU - Capello, Michela

AU - Yu, Chuan Yih

AU - Cai, Yining

AU - Hsiao, Fu Chung

AU - Patel, Nikul

AU - Park, Soyoung

AU - Peng, Qian

AU - Dennison, Jennifer B.

AU - Kato, Taketo

AU - Tai, Mei Chee

AU - Taguchi, Ayumu

AU - Kadara, Humam

AU - Wistuba, Ignacio I.

AU - Katayama, Hiroyuki

AU - Do, Kim Anh

AU - Hanash, Samir M.

AU - Ostrin, Edwin J.

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AB - 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.

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

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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