Abstract
A differential analysis of TCR repertoire between patients with EGFR-mutant and KRAS-mutant non–small-cell lung cancer.
Author
person
Yuancai Xie
Peking University Shenzhen Hospital, Shenzhen, China
info_outline
Yuancai Xie, Yingmei Li, Linfeng Dong, Shifu Chen, Jixian Liu
Full text
Authors
person
Yuancai Xie
Peking University Shenzhen Hospital, Shenzhen, China
info_outline
Yuancai Xie, Yingmei Li, Linfeng Dong, Shifu Chen, Jixian Liu
Organizations
Peking University Shenzhen Hospital, Shenzhen, China, HaploX Biotechnology Co., Ltd, Shenzhen, Guangdong, China, HaploX Biotechnology, Shenzhen, China, HaploX Biotechnology Co. Ltd., Shenzhen, China
Abstract Disclosures
Research Funding
No funding received
None.
Background:
T-cell receptor (TCR) repertoire could partially represent tumor micro-environment. EGFR and KRAS are common driver genes mutated and often mutually exclusive in non-small cell lung cancer (NSCLC). There’s a hypothesis that the immune system responds differently according to different mutations. Here we investigated the TCR features, including diversity, clonality, evenness and sequence similarity in EGFR and KRAS mutated NSCLC patients, to better understand the immune response in carcinogenesis.
Methods:
A total of 71 EGFR-mutant and 31 KRAS-mutant NSCLC tissue samples underwent multiplex PCR based TCR-β sequencing. TCR-β cdr3 amino acid sequences were obtained from the sequencing data using MiXCR and VDJtools. To compare TCR repertoires in EGFR-mutant and KRAS-mutant groups, each assemble CDR3 amino acid sequence was taken as a word, and each repertoire was taken as a document. Each repertoire was compared with every other one as a sample pair. TF-IDF (term frequency-inverse document frequency) document vectors was built for each sample and cosine similarity scores were computed for sample pairs.
Results:
The total cosine similarity score within EGFR-mutant group is 11.07 and average cosine similarity score is 0.0044±0.01, while in the KRAS-group, the total cosine similarity score is 13.41 and average cosine similarity score is 0.029±0.04. Between these two groups, the total cosine similarity score is 8.76 and average cosine similarity score is 0.0019±0.0009. See table for summary. The intergroup similarity score is significantly less than that within each group respectively (p < 1E10).
Conclusions:
Our results demonstrated that the TCR repertoire was clearly associated with cancer mutational profile. The mechanism of how mutations affect the immune system and shape the TCR repertoire is yet to be investigated.
The similarity score of TCR repertoire within and between groups.
EGFR group
KRAS group
EGFR vs KRAS
Total cosine similarity score
11.07
13.41
8.76
Average cosine similarity score
0.0044±0.01
0.029±0.04
0.0019±0.0009
4 organizations
2 drugs
2 targets
Organization
Peking University Shenzhen HospitalOrganization
HaploX Biotechnology Co., Ltd., Shenzhen, ChinaOrganization
HaploX Biotechnology, Shenzhen, ChinaOrganization
HaploX Biotechnology Co. Ltd.Drug
KRASTarget
KRAS G12C