Molecular characterization of Kita-Kyushu lung cancer antigen (KK-LC-1) expressing carcinomas

Robert Hsu; Yasmine Baca; Joanne Xiu; Rongfu Wang; J. Nicholas Bodor; Chul Kim; Hina Khan; Hirva Mamdani; Misako Nagasaka; Sonam Puri; Stephen V. Liu; W. Michael Korn; Jorge J. Nieva

doi:10.18632/ONCOTARGET.28132

Molecular characterization of Kita-Kyushu lung cancer antigen (KK-LC-1) expressing carcinomas

Robert Hsu, Yasmine Baca, Joanne Xiu, Rongfu Wang, J. Nicholas Bodor, Chul Kim, Hina Khan, Hirva Mamdani, Misako Nagasaka, Sonam Puri, Stephen V. Liu, W. Michael Korn, Jorge J. Nieva

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

5 Scopus citations

Abstract

Cancer/testis antigens (CTAs) are strongly expressed in some solid tumors but minimally expressed in normal tissue, making them appealing therapeutic targets. KK-LC-1 (CXorf61) has cytoplasmic expression in gastric, breast, and lung cancer. We characterized the molecular subtypes of non-small cell lung cancer (NSCLC) expressing KK-LC-1 to inform rational clinical trials of T-cell receptor therapy (TCR-T) targeting KK-LC-1. 9790 NSCLC tumors that underwent whole transcriptome sequencing (Illumina NovaSeq) and NextGen DNA sequencing (NextSeq, 592 Genes and NovaSEQ, WES) at Caris Life Sciences (Phoenix, AZ) were analyzed. Tumors were split into quartiles based on KK-LC-1 expression and pathological and molecular differences were investigated. Adenocarcinoma had significantly higher KK-LC-1 expression than squamous cell carcinoma (median, 3.25 vs. 1.17 transcripts per million (TPM), p < 0.0001). Tumors with the highest quartile of KK-LC-1 expression had a greater proportion of tumors with high tumor mutation burden (TMB) (≥10 mutations per megabase; 44% vs. 28% in Q1, p < 0.001). Increased KK-LC-1 expression was associated with increased M1 macrophage abundance. Higher levels of KK-LC-1 expression were seen in pan-wild type and KRAS mutated tumors and associated with high TMB. TCR-T therapy directed against KK-LC-1 should be considered in patients whose clinical features reflect these characteristics.

Original language	English (US)
Pages (from-to)	2449-2458
Number of pages	10
Journal	Oncotarget
Volume	12
Issue number	25
DOIs	https://doi.org/10.18632/ONCOTARGET.28132
State	Published - Dec 7 2021

Keywords

Biomarkers for immunotherapy
Cancer testis antigen
Diagnostic biomarkers
Lung cancer
Tumor microenvironment

ASJC Scopus subject areas

Oncology

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10.18632/ONCOTARGET.28132

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@article{00490f7509be441588ae4a25a25bc4f2,

title = "Molecular characterization of Kita-Kyushu lung cancer antigen (KK-LC-1) expressing carcinomas",

abstract = "Cancer/testis antigens (CTAs) are strongly expressed in some solid tumors but minimally expressed in normal tissue, making them appealing therapeutic targets. KK-LC-1 (CXorf61) has cytoplasmic expression in gastric, breast, and lung cancer. We characterized the molecular subtypes of non-small cell lung cancer (NSCLC) expressing KK-LC-1 to inform rational clinical trials of T-cell receptor therapy (TCR-T) targeting KK-LC-1. 9790 NSCLC tumors that underwent whole transcriptome sequencing (Illumina NovaSeq) and NextGen DNA sequencing (NextSeq, 592 Genes and NovaSEQ, WES) at Caris Life Sciences (Phoenix, AZ) were analyzed. Tumors were split into quartiles based on KK-LC-1 expression and pathological and molecular differences were investigated. Adenocarcinoma had significantly higher KK-LC-1 expression than squamous cell carcinoma (median, 3.25 vs. 1.17 transcripts per million (TPM), p < 0.0001). Tumors with the highest quartile of KK-LC-1 expression had a greater proportion of tumors with high tumor mutation burden (TMB) (≥10 mutations per megabase; 44% vs. 28% in Q1, p < 0.001). Increased KK-LC-1 expression was associated with increased M1 macrophage abundance. Higher levels of KK-LC-1 expression were seen in pan-wild type and KRAS mutated tumors and associated with high TMB. TCR-T therapy directed against KK-LC-1 should be considered in patients whose clinical features reflect these characteristics.",

keywords = "Biomarkers for immunotherapy, Cancer testis antigen, Diagnostic biomarkers, Lung cancer, Tumor microenvironment",

author = "Robert Hsu and Yasmine Baca and Joanne Xiu and Rongfu Wang and Bodor, {J. Nicholas} and Chul Kim and Hina Khan and Hirva Mamdani and Misako Nagasaka and Sonam Puri and Liu, {Stephen V.} and Korn, {W. Michael} and Nieva, {Jorge J.}",

note = "Funding Information: This work was funded in part by the USC Norris Comprehensive Cancer Center (Core) Grant, P30 CA014089. Publisher Copyright: {\textcopyright} 2021 Hsu et al.",

year = "2021",

month = dec,

day = "7",

doi = "10.18632/ONCOTARGET.28132",

language = "English (US)",

volume = "12",

pages = "2449--2458",

journal = "Oncotarget",

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number = "25",

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TY - JOUR

T1 - Molecular characterization of Kita-Kyushu lung cancer antigen (KK-LC-1) expressing carcinomas

AU - Hsu, Robert

AU - Baca, Yasmine

AU - Xiu, Joanne

AU - Wang, Rongfu

AU - Bodor, J. Nicholas

AU - Kim, Chul

AU - Khan, Hina

AU - Mamdani, Hirva

AU - Nagasaka, Misako

AU - Puri, Sonam

AU - Liu, Stephen V.

AU - Korn, W. Michael

AU - Nieva, Jorge J.

PY - 2021/12/7

Y1 - 2021/12/7

N2 - Cancer/testis antigens (CTAs) are strongly expressed in some solid tumors but minimally expressed in normal tissue, making them appealing therapeutic targets. KK-LC-1 (CXorf61) has cytoplasmic expression in gastric, breast, and lung cancer. We characterized the molecular subtypes of non-small cell lung cancer (NSCLC) expressing KK-LC-1 to inform rational clinical trials of T-cell receptor therapy (TCR-T) targeting KK-LC-1. 9790 NSCLC tumors that underwent whole transcriptome sequencing (Illumina NovaSeq) and NextGen DNA sequencing (NextSeq, 592 Genes and NovaSEQ, WES) at Caris Life Sciences (Phoenix, AZ) were analyzed. Tumors were split into quartiles based on KK-LC-1 expression and pathological and molecular differences were investigated. Adenocarcinoma had significantly higher KK-LC-1 expression than squamous cell carcinoma (median, 3.25 vs. 1.17 transcripts per million (TPM), p < 0.0001). Tumors with the highest quartile of KK-LC-1 expression had a greater proportion of tumors with high tumor mutation burden (TMB) (≥10 mutations per megabase; 44% vs. 28% in Q1, p < 0.001). Increased KK-LC-1 expression was associated with increased M1 macrophage abundance. Higher levels of KK-LC-1 expression were seen in pan-wild type and KRAS mutated tumors and associated with high TMB. TCR-T therapy directed against KK-LC-1 should be considered in patients whose clinical features reflect these characteristics.

AB - Cancer/testis antigens (CTAs) are strongly expressed in some solid tumors but minimally expressed in normal tissue, making them appealing therapeutic targets. KK-LC-1 (CXorf61) has cytoplasmic expression in gastric, breast, and lung cancer. We characterized the molecular subtypes of non-small cell lung cancer (NSCLC) expressing KK-LC-1 to inform rational clinical trials of T-cell receptor therapy (TCR-T) targeting KK-LC-1. 9790 NSCLC tumors that underwent whole transcriptome sequencing (Illumina NovaSeq) and NextGen DNA sequencing (NextSeq, 592 Genes and NovaSEQ, WES) at Caris Life Sciences (Phoenix, AZ) were analyzed. Tumors were split into quartiles based on KK-LC-1 expression and pathological and molecular differences were investigated. Adenocarcinoma had significantly higher KK-LC-1 expression than squamous cell carcinoma (median, 3.25 vs. 1.17 transcripts per million (TPM), p < 0.0001). Tumors with the highest quartile of KK-LC-1 expression had a greater proportion of tumors with high tumor mutation burden (TMB) (≥10 mutations per megabase; 44% vs. 28% in Q1, p < 0.001). Increased KK-LC-1 expression was associated with increased M1 macrophage abundance. Higher levels of KK-LC-1 expression were seen in pan-wild type and KRAS mutated tumors and associated with high TMB. TCR-T therapy directed against KK-LC-1 should be considered in patients whose clinical features reflect these characteristics.

KW - Biomarkers for immunotherapy

KW - Cancer testis antigen

KW - Diagnostic biomarkers

KW - Lung cancer

KW - Tumor microenvironment

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U2 - 10.18632/ONCOTARGET.28132

DO - 10.18632/ONCOTARGET.28132

M3 - Article

C2 - 34917263

AN - SCOPUS:85122504681

SN - 1949-2553

VL - 12

SP - 2449

EP - 2458

JO - Oncotarget

JF - Oncotarget

IS - 25

ER -

Molecular characterization of Kita-Kyushu lung cancer antigen (KK-LC-1) expressing carcinomas

Abstract

Keywords

ASJC Scopus subject areas

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