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Somatic mutation profiling, tumor-infiltrating leukocytes, tertiary lymphoid structures and PD-L1 protein expression in HER2-amplified colorectal cancer

The status of human epidermal growth factor receptor 2 (HER2) for the prognosis in colorectal cancer (CRC) is controversial, and the characteristics of the somatic mutation spectrum, tumor-infiltrating leukocytes, tertiary lymphoid structures and PD-L1 protein are unknown in HER2-amplified colorecta...

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Autores principales: Liu, Xiao-Ting, Kou, Zhi-Yong, Zhang, Hushan, Dong, Jian, Zhang, Jian-Hua, Peng, You-Jun, Ma, Shu Min, Liang, Lei, Meng, Xuan-Yu, Zhou, Yuan, Yang, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10162038/
https://www.ncbi.nlm.nih.gov/pubmed/37151285
http://dx.doi.org/10.7717/peerj.15261
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author Liu, Xiao-Ting
Kou, Zhi-Yong
Zhang, Hushan
Dong, Jian
Zhang, Jian-Hua
Peng, You-Jun
Ma, Shu Min
Liang, Lei
Meng, Xuan-Yu
Zhou, Yuan
Yang, Jun
author_facet Liu, Xiao-Ting
Kou, Zhi-Yong
Zhang, Hushan
Dong, Jian
Zhang, Jian-Hua
Peng, You-Jun
Ma, Shu Min
Liang, Lei
Meng, Xuan-Yu
Zhou, Yuan
Yang, Jun
author_sort Liu, Xiao-Ting
collection PubMed
description The status of human epidermal growth factor receptor 2 (HER2) for the prognosis in colorectal cancer (CRC) is controversial, and the characteristics of the somatic mutation spectrum, tumor-infiltrating leukocytes, tertiary lymphoid structures and PD-L1 protein are unknown in HER2-amplified colorectal cancer (HACC). In order to explore these characteristics along with their correlation with clinicopathological factors and prognosis in HACC. Samples of 812 CRC patients was collected. After immunohistochemistry (IHC), 59 of 812 were found to be HER2-positive, then 26 of 59 samples were further determined to be HER2 amplification by fluorescence in situ hybridization (FISH). Somatic mutation profiling of HACC was analysed using whole exome sequencing (WES). Multiplex fluorescence immunohistochemistry (mIHC) was used for tumor-infiltrating leukocytes and tertiary lymphoid structures (TLSs), while PD-L1 protein was detected by IHC. Our results indicate that the detection rates of HER2 positivity by IHC and FISH were 7.3% and 3.2% respectively, and HER2 amplification is correlated with distant tumour metastasis. The somatic mutation profiling revealed no differences between HACC and HER2-negative CRC. However, TP 53 strongly correlated with poor prognosis in HACC. Furthermore, tumor-infiltrating T cells and TLSs in the tumor immune microenvironment, as well as PD-L1 expression, were higher in HACC than in HER2-negative controls. However, none of them were associated with the prognosis of HACC. In all, HER2 amplification is correlated with distant metastasis and TP53 gene mutation may be a potential protective mechanism of HACC.
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spelling pubmed-101620382023-05-06 Somatic mutation profiling, tumor-infiltrating leukocytes, tertiary lymphoid structures and PD-L1 protein expression in HER2-amplified colorectal cancer Liu, Xiao-Ting Kou, Zhi-Yong Zhang, Hushan Dong, Jian Zhang, Jian-Hua Peng, You-Jun Ma, Shu Min Liang, Lei Meng, Xuan-Yu Zhou, Yuan Yang, Jun PeerJ Gastroenterology and Hepatology The status of human epidermal growth factor receptor 2 (HER2) for the prognosis in colorectal cancer (CRC) is controversial, and the characteristics of the somatic mutation spectrum, tumor-infiltrating leukocytes, tertiary lymphoid structures and PD-L1 protein are unknown in HER2-amplified colorectal cancer (HACC). In order to explore these characteristics along with their correlation with clinicopathological factors and prognosis in HACC. Samples of 812 CRC patients was collected. After immunohistochemistry (IHC), 59 of 812 were found to be HER2-positive, then 26 of 59 samples were further determined to be HER2 amplification by fluorescence in situ hybridization (FISH). Somatic mutation profiling of HACC was analysed using whole exome sequencing (WES). Multiplex fluorescence immunohistochemistry (mIHC) was used for tumor-infiltrating leukocytes and tertiary lymphoid structures (TLSs), while PD-L1 protein was detected by IHC. Our results indicate that the detection rates of HER2 positivity by IHC and FISH were 7.3% and 3.2% respectively, and HER2 amplification is correlated with distant tumour metastasis. The somatic mutation profiling revealed no differences between HACC and HER2-negative CRC. However, TP 53 strongly correlated with poor prognosis in HACC. Furthermore, tumor-infiltrating T cells and TLSs in the tumor immune microenvironment, as well as PD-L1 expression, were higher in HACC than in HER2-negative controls. However, none of them were associated with the prognosis of HACC. In all, HER2 amplification is correlated with distant metastasis and TP53 gene mutation may be a potential protective mechanism of HACC. PeerJ Inc. 2023-05-02 /pmc/articles/PMC10162038/ /pubmed/37151285 http://dx.doi.org/10.7717/peerj.15261 Text en ©2023 Liu et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Gastroenterology and Hepatology
Liu, Xiao-Ting
Kou, Zhi-Yong
Zhang, Hushan
Dong, Jian
Zhang, Jian-Hua
Peng, You-Jun
Ma, Shu Min
Liang, Lei
Meng, Xuan-Yu
Zhou, Yuan
Yang, Jun
Somatic mutation profiling, tumor-infiltrating leukocytes, tertiary lymphoid structures and PD-L1 protein expression in HER2-amplified colorectal cancer
title Somatic mutation profiling, tumor-infiltrating leukocytes, tertiary lymphoid structures and PD-L1 protein expression in HER2-amplified colorectal cancer
title_full Somatic mutation profiling, tumor-infiltrating leukocytes, tertiary lymphoid structures and PD-L1 protein expression in HER2-amplified colorectal cancer
title_fullStr Somatic mutation profiling, tumor-infiltrating leukocytes, tertiary lymphoid structures and PD-L1 protein expression in HER2-amplified colorectal cancer
title_full_unstemmed Somatic mutation profiling, tumor-infiltrating leukocytes, tertiary lymphoid structures and PD-L1 protein expression in HER2-amplified colorectal cancer
title_short Somatic mutation profiling, tumor-infiltrating leukocytes, tertiary lymphoid structures and PD-L1 protein expression in HER2-amplified colorectal cancer
title_sort somatic mutation profiling, tumor-infiltrating leukocytes, tertiary lymphoid structures and pd-l1 protein expression in her2-amplified colorectal cancer
topic Gastroenterology and Hepatology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10162038/
https://www.ncbi.nlm.nih.gov/pubmed/37151285
http://dx.doi.org/10.7717/peerj.15261
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