Identification of Tumor Antigens and Immune Subtypes of Glioblastoma for mRNA Vaccine Development

Lin, Han; Wang, Kun; Xiong, Yujiu; Zhou, Liting; Yang, Yong; Chen, Shanwei; Xu, Peihong; Zhou, Yujun; Mao, Rui; Lv, Guangzhao; Wang, Peng; Zhou, Dong

doi:10.3389/fimmu.2022.773264

Cited by 25 publications

(26 citation statements)

References 86 publications

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“…PLB1 (phospholipase B1) is a secreted membrane-associated phospholipase that is involved in choline metabolism in tumors [ 32 ]. PLB1 mutation was reported to be associated with poor survival in non-small cell lung cancer and glioblastoma multiform [ 33 , 34 ]. As shown in Table 2 , our results demonstrated that the genetic mutations of these genes mentioned above ( CDH1 , ARID1A , FAT4 , KMT2C , TP53 , KMT2D , MACF1 , and PLB1 ) were associated with the down regulation of the associated protein function, which may be involved in the up-regulation or down-regulation in the mechanism of cancer developing.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the mutation patterns between tumor tissue and cell-free DNA in stage IV gastric cancer

Kung

Fang

Hung

et al. 2023

Aging

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Compared to stage I-III gastric cancer (GC), the level of cell-free DNA (cfDNA) was significantly higher in stage IV GC. The mutation patterns of different metastatic patterns between cfDNA and tumor DNA in stage IV GC have not yet been reported. We used next-generation sequencing (NGS) to analyze cfDNA and tumor DNA in 56 stage IV GC patients. Tumor DNA and cfDNA were analyzed using a 29-gene NGS panel. In tumor samples, the most commonly mutated gene was TP53 (64%), followed by ARID1A (62%), KMT2C (60%) and KMT2D (58%). In cfDNA samples, the most commonly mutated genes were FAT4 (19%) and MACF1 (19%), followed by KMT2D (18%), ARID1A (14%) and LRP1B (14%). The concordance of mutation patterns in these 29 genes was 42.0% between cfDNA and tumor DNA. A specificity of 100% was found when using the mutation status of cfDNA to predict mutations in tumor samples. The sensitivity of the mutation status of cfDNA to predict mutation in tumor samples was highest in FAT4 (88.9%), followed by MACF1 (80%), CDH1 (75%) and PLB1 (75%). For cfDNA with PLB1 mutations, patients were more likely to develop distant lymphatic metastasis than peritoneal metastasis. Patients with multiple-site metastases had significantly more mutated spots than patients with single-site metastasis. Due to the high sensitivity and specificity of some genes in the prediction of mutation in tumor samples, monitoring the mutation pattern of cfDNA may be useful in the stage IV GC treatment.

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Section: Discussionmentioning

confidence: 99%

Comparison of the mutation patterns between tumor tissue and cell-free DNA in stage IV gastric cancer

Kung

Fang

Hung

et al. 2023

Aging

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“…Both such biomarkers were upregulated in mesenchymal compared to classical phenotype. Previously, CD300E was detected as the receptor stimulating monocyte activity and was even suggested as a potential antigen for an RNA vaccine against GBM [35,36].…”

Section: Gene Biomarkersmentioning

confidence: 99%

Next-Generation Grade and Survival Expression Biomarkers of Human Gliomas Based on Algorithmically Reconstructed Molecular Pathways

Zolotovskaia

Kovalenko

Tkachev³

et al. 2022

IJMS

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In gliomas, expression of certain marker genes is strongly associated with survival and tumor type and often exceeds histological assessments. Using a human interactome model, we algorithmically reconstructed 7494 new-type molecular pathways that are centered each on an individual protein. Each single-gene expression and gene-centric pathway activation was tested as a survival and tumor grade biomarker in gliomas and their diagnostic subgroups (IDH mutant or wild type, IDH mutant with 1p/19q co-deletion, MGMT promoter methylated or unmethylated), including the three major molecular subtypes of glioblastoma (proneural, mesenchymal, classical). We used three datasets from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas, which in total include 527 glioblastoma and 1097 low grade glioma profiles. We identified 2724 such gene and 2418 pathway survival biomarkers out of total 17,717 genes and 7494 pathways analyzed. We then assessed tumor grade and molecular subtype biomarkers and with the threshold of AUC > 0.7 identified 1322/982 gene biomarkers and 472/537 pathway biomarkers. This suggests roughly two times greater efficacy of the reconstructed pathway approach compared to gene biomarkers. Thus, we conclude that activation levels of algorithmically reconstructed gene-centric pathways are a potent class of new-generation diagnostic and prognostic biomarkers for gliomas.

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“…In recent years, accumulating attention has been paid by scholars worldwide, to the development of the cancer vaccine, which attempts to enhance the patients’ immunity against cancerous cells [ 8 ]. The discovery of tumor associated antigens (TAAs) represents one of the major challenges in the design of a vaccine, and several studies have introduced new ideas to the identification of TAAs [ 9 , 10 , 11 ]. In the family of cancer vaccines, compared to other members, messenger RNA (mRNA) vaccines possess some unique advantages such as: synchronously eliciting the humoral and cell immunity, without a risk of integration into the nuclear genome and encoding more epitopes to be presented by antigen presenting cells (APCs) [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Five Tumor Antigens for Development and Two Immune Subtypes for Personalized Medicine of mRNA Vaccines in Papillary Renal Cell Carcinoma

Yuan

Jiang³

2023

JPM

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Increasing evidence has revealed the promise of mRNA-type cancer vaccines as a new direction for cancer immune treatment in several solid tumors, however, its application in papillary renal cell carcinoma (PRCC) remains unclear. The purpose of this study was to identify potential tumor antigens and robust immune subtypes for the development and appropriate use of anti-PRCC mRNA vaccines, respectively. Raw sequencing data and clinical information of PRCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The cBioPortal was utilized for the visualization and comparison of genetic alterations. The TIMER was used to assess the correlation between preliminary tumor antigens and the abundance of infiltrated antigen presenting cells (APCs). Immune subtypes were determined by the consensus clustering algorithm, and clinical and molecular discrepancies were further explored for a deeper understanding of immune subtypes. Five tumor antigens, including ALOX15B, HS3ST2, PIGR, ZMYND15 and LIMK1, were identified for PRCC, which were correlated with patients’ prognoses and infiltration levels of APCs. Two immune subtypes (IS1 and IS2) were disclosed with obviously distinct clinical and molecular characteristics. Compared with IS2, IS1 exhibited a significantly immune-suppressive phenotype, which largely weakened the efficacy of the mRNA vaccine. Overall, our study provides some insights for the design of anti-PRCC mRNA vaccines and, more importantly, the selection of suitable patients to be vaccinated.

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Identification of Tumor Antigens and Immune Subtypes of Glioblastoma for mRNA Vaccine Development

Cited by 25 publications

References 86 publications

Comparison of the mutation patterns between tumor tissue and cell-free DNA in stage IV gastric cancer

Comparison of the mutation patterns between tumor tissue and cell-free DNA in stage IV gastric cancer

Next-Generation Grade and Survival Expression Biomarkers of Human Gliomas Based on Algorithmically Reconstructed Molecular Pathways

Identification of Five Tumor Antigens for Development and Two Immune Subtypes for Personalized Medicine of mRNA Vaccines in Papillary Renal Cell Carcinoma

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