Dataset Information

Heterogeneity of neoantigen landscape between primary lesions and their matched metastases in lung cancer.

ABSTRACT: Background:Personalized cancer vaccines based on tumor-derived neoantigens have shown strong and long-lasting antitumor effect in patients with some solid tumors. However, whether neoantigens identified from primary lesions could represent their metastatic lesions, and consequently the effect of vaccine therapy remained unknown. Methods:To investigate whether neoantigens identified from primary tumors are similar to their matched metastases in lung cancer, we identified 79 samples from 24 cases. All of samples were collected before any systemic therapy. Major criteria for neoantigen identification included: derived from tumor-specific mutations, fold change >10 comparing to germline expression level, high predicted human leukocyte antigen (HLA) binding affinity and peptide of 9-11 amino acids in length. Results:We found a wide range of tumor neoantigen burden in both primaries and metastases. The counts, overall distribution pattern and predicted HLA binding affinity of neoantigens were similar between primaries and metastases. However, only 20% of shared neoantigens (presented in both primaries and metastases) was observed, which were mainly derived from single nucleotide variants (SNVs) and fusions. A variety of corresponding HLA alleles were observed and 50.0% of cases were HLA-C*06:02. Finally, we observed the neoantigen intrametastases homogeneity in patients with sole brain metastases. Conclusions:Neoantigen landscape in terms of the number, type and predicted HLA binding affinity was similar between primaries and metastases, but the percentage of shared neoantigens is only modest, suggesting vaccine development based solely on primary tumor neoantigen may not offer optimal therapeutic outcome, and shared neoantigen needs to be seriously considered.

SUBMITTER: Jiang T

PROVIDER: S-EPMC7225166 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Heterogeneity of neoantigen landscape between primary lesions and their matched metastases in lung cancer.

Jiang Tao T Cheng Ruirui R Pan Yuanwei Y Zhang Henghui H He Ying Y Su Chunxia C Ren Shengxiang S Zhou Caicun C

Translational lung cancer research 20200401 2

<h4>Background</h4>Personalized cancer vaccines based on tumor-derived neoantigens have shown strong and long-lasting antitumor effect in patients with some solid tumors. However, whether neoantigens identified from primary lesions could represent their metastatic lesions, and consequently the effect of vaccine therapy remained unknown.<h4>Methods</h4>To investigate whether neoantigens identified from primary tumors are similar to their matched metastases in lung cancer, we identified 79 samples ...[more]

PMID: 32420064

Similar Datasets

Project description:Whether the expression status of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2) receptor and Ki-67 show concordance between the primary tumors and the synchronous axillary lymph node (ALN) metastases has been discussed in numerous studies. However, to date, the results of these studies remain controversial. Therefore, the present study aimed to investigate whether the expression of ER, PR, HER-2 and Ki-67 was in concordance between the primary tumors and synchronous ALN metastases in patients with operable breast cancer (BC). A total of 60 tissue samples were collected from patients with primary operable BC diagnosed with primary tumors and synchronous ALN metastases. The expression levels of the four biomarkers, ER, PR, HER-2 and Ki-67, were assessed in primary lesions and synchronous ALN metastases samples using immunohistochemistry. The cut-off values were set to 10% for ER and PR, while the labeling index of Ki-67 was set to 14%. The immunostaining intensity of ER and PR was scored as negative (?), 1+, 2+ and 3+. The criteria for HER-2 testing in BC were implemented according to the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) guidelines. The concordance rates for ER, PR and HER-2 were 96.7 (58/60), 96.7 (58/60) and 90% (54/60), respectively. In addition, the kappa values of consistency in the primary lesions and the synchronous ALN metastases were 0.773 for ER, 0.654 for PR and 0.785 for HER-2. Furthermore, the P-values of ER, PR and Ki-67 numerical variables between the two groups were 0.393, 0.400 and 0.331, respectively, as demonstrated using a non-parametric Wilcoxon signed rank test. The findings of the present study demonstrated a high degree of concordance between the expression of ER, PR, HER-2 and Ki-67 in the primary tumors and that in the synchronous ALN metastases, suggesting that the BC primary tumor biomarkers may be used for the prognosis of synchronous ALN metastases in patients with operable BC.

Project description:Glioblastoma (GBM) is the most malignant human brain tumour, characterized by rapid progression, invasion, intense angiogenesis, high genomic instability, and resistance to therapies. Despite countless experimental researches for new therapeutic strategies and promising clinical trials, the prognosis remains extremely poor, with a mean survival of less than 14 months. GBM aggressive behaviour is due to a subpopulation of tumourigenic stem-like cells, GBM stem cells (GSCs), which hierarchically drive onset, proliferation, and tumour recurrence. The morbidity and mortality of this disease strongly encourage exploring genetic characteristics of GSCs. Here, using array-CGH platform, we investigated genetic and genomic aberration profiles of GBM parent tumour (n = 10) and their primarily derived GSCs. Statistical analysis was performed by using R software and complex heatmap and corrplot packages. Pearson correlation and K-means algorithm were exploited to compare genetic alterations and to group similar genetic profiles in matched pairs of GBM and derived GSCs. We identified, in both GBM and matched GSCs, recurrent copy number alterations, as chromosome 7 polysomy, chromosome 10 monosomy, and chromosome 9p21deletions, which are typical features of primary GBM, essential for gliomagenesis. These observations suggest a condition of strong genomic instability both in GBM as GSCs. Our findings showed the robust similarity between GBM mass and GSCs (Pearson corr.≥0.65) but also highlighted a marked variability among different patients. Indeed, the heatmap reporting Gain/Loss State for 21022 coding/noncoding genes demonstrated high interpatient divergence. Furthermore, K-means algorithm identified an impairment of pathways related to the development and progression of cancer, such as angiogenesis, as well as pathways related to the immune system regulation, such as T cell activation. Our data confirmed the preservation of the genomic landscape from tumour tissue to GSCs, supporting the relevance of this cellular model to test in vitro new target therapies for GBM.

Dataset Information

Heterogeneity of neoantigen landscape between primary lesions and their matched metastases in lung cancer.

Publications

Heterogeneity of neoantigen landscape between primary lesions and their matched metastases in lung cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets