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  • Bai, Yongrui  (3)
  • 1
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-9-2)
    Abstract: Radiotherapy plays an important effect on the standard therapy of esophageal squamous cell carcinoma (ESCC). However, the efficacy of the therapy is limited and a few patients do not achieve satisfactory treatment results due to the existence of radiation resistance. Therefore, it is necessary to identify the potential predictive biomarkers and treatment targets for ESCC. Methods We performed the whole-exome sequencing to determine the germline and somatic mutations in ESCC. Functional enrichment and pathway-based protein-protein interaction analyses were used to ascertain potential regulatory networks. Cell survival and cell death after treatment with radiotherapy were determined by CCK-8 and LDH release assays in ESCC cells. The correlations of NOTCH1 and tumor immune infiltration were also analyzed in ESCC. Results Our results showed that 344 somatic and 65 germline differentially mutated genes were detected to be radiosensitivity-related loci. The tumor mutational burdens (TMB) or microsatellite instability (MSI) were not significantly correlated with the response to radiotherapy in ESCC patients. Pathway-based protein-protein interaction analyses implied several hub genes with most nodes (such as PIK3CA, NOTCH1, STAT3 and KDR). The in vitro studies showed that the knockdown of NOTCH1 inhibited cell survival and rendered more cell death after the treatment with radiotherapy in ESCC cells, while NOTCH1 overexpression had the opposite effects. Moreover, NOTCH1, frequently up-regulated in ESCC, was negatively correlated with activated B cell and immature dendritic cell in ESCC. High expression of NOTCH1 was accompanied with the low levels of some immunotherapy-related cells, including CD8(+) T cells and NK cells. Conclusions These results indicate the differences of the germline mutations and somatic mutations between the radiosensitive and radioresistence groups in ESCC and imply that NOTCH1 plays important roles in regulating the radiosensitivity of ESCC. The findings might provide the biomarkers and potential treatment targets for improving the sensitivity to radiotherapy in ESCC.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 2
    In: Journal of the National Cancer Center, Elsevier BV, Vol. 2, No. 4 ( 2022-12), p. 205-215
    Type of Medium: Online Resource
    ISSN: 2667-0054
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 3101541-4
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-8-9)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-8-9)
    Abstract: Pancreatic cancer (PC) is one of the most lethal human cancers, and radiation therapy (RT) is an important treating option. Many patients diagnosed with PC do not achieve objective responses because of the existence of intrinsic and acquired radioresistance. Therefore, biomarkers, which predict radiotherapy benefit in PC, are eagerly needed to be identified. Methods Whole-exome sequencing of six pancreatic ductal adenocarcinoma patients (PDAC) (three with a good response and three with a poor response) who had received radical surgery and then radiotherapy has been performed as standard of care treatment. Somatic and germline variants and the mutational signatures were analyzed with bioinformatics tools and public databases. Functional enrichment and pathway-based protein-protein interaction analyses were utilized to address the possibly mechanism in radioresistance. MTT, LDH, and colony formation assay were applied to evaluate cell growth and colony formation ability. Results In the present study, somatic mutations located in 441 genes were detected to be radiosensitivity-related loci. Seventeen genes, including the Smad protein family members (SMAD3 and SMAD4), were identified to influence the radiosensitivity in PDAC. The SMAD3 and SMAD4 genes mutate differently between radiosensitive and radioresistant PDAC patients. Mutation of SMAD3 potentiates the effects of ionizing radiation (IR) on cell growth and colony formation in PDAC cells, whereas mutation of SMAD4 had the opposite effects. SMAD3 and SMAD4 regulate the radiosensitivity of PDAC, at least in part, by P21 and FOXO3a, respectively. Conclusions These results indicate that mutations of SMAD3 and SMAD4 likely cause the difference of response to radiotherapy in PDAC, which might be considered as the biomarkers and potential targets for the radiotherapy of pancreatic cancer.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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