Precision radiotherapy for non-small cell lung cancer

Yang, Wen-Chi; Hsu, Feng‐Ming; Yang, Pan‐Chyr

doi:10.1186/s12929-020-00676-5

Cited by 47 publications

(37 citation statements)

References 124 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Radiotherapy triggers immune responses and has significant anti-tumor effects during LUAD treatment [ 5 ]. However, the molecular mechanisms remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

RRM2 silencing suppresses malignant phenotype and enhances radiosensitivity via activating cGAS/STING signaling pathway in lung adenocarcinoma

Jiang

Zhang

et al. 2021

Cell Biosci

View full text Add to dashboard Cite

Background As one of the most common malignancy, lung adenocarcinoma (LUAD) is characterized by low 5-year survival rate. This research aimed to investigate the effects of ribonucleotide reductase regulatory subunit M2 (RRM2) on malignant biological behaviors and activation of cGAS/STING pathway. We also explored the synergistic sensitization mechanisms of RRM2 and radiotherapy. Methods Bioinformatic tools were used to evaluate the clinical significance of RRM2 in LUAD patients. The roles of RRM2 in malignant phenotype and DNA damage in LUAD cells were investigated with cell proliferation, colony formation, immunofluorescence, modified Boyden chamber and comet assays. The mouse models were used to evaluate the biological significance of RRM2 in vivo. Cytotoxic T cell infiltration was evaluated via flow cytometric analysis and immunohistochemistry staining in C57BL/6 mice. We also explored the synergistic effects of RRM2 silencing and radiation on LUAD cells with apoptosis assay and immunoblotting in vitro. Results Bioinformatic analysis revealed that RRM2 had diagnostic values for LUAD patients. Higher levels of RRM2 predicted worse prognosis. RRM2 silencing inhibited LUAD cell proliferation, invasion and migration. RRM2 knockdown induced S phase arrest and DNA damage. RRM2 silencing induced cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway, and the downstream targets were regulated in a STING-dependent manner. Knockdown of RRM2 suppressed tumor growth in the xenograft tumor models. RRM2 deficiency increased CD8 + T cells in the tumor tissues and spleens. Furthermore, RRM2 silencing had synergistic effects with radiation on inhibiting cell proliferation and promoting apoptosis. Meanwhile, this combination promoted the activation of cGAS/STING signaling pathway synergistically, and simultaneously increased expression of IFNβ, CCL5 and CXCL10. Conclusion Our results demonstrated that RRM2 silencing had anti-tumor values and activated the cGAS/STING signaling pathway. RRM2 silencing increased CD8 + T cells infiltration. RRM2 silencing cooperated with radiation to inhibit LUAD cell proliferation, promote apoptosis and enhance the activation of cGAS/STING signaling pathway. RRM2 could be a promising target for tumor regression through cancer immunotherapy in LUAD.

show abstract

“…Radiotherapy triggers immune responses and has significant anti-tumor effects during LUAD treatment [ 5 ]. However, the molecular mechanisms remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

RRM2 silencing suppresses malignant phenotype and enhances radiosensitivity via activating cGAS/STING signaling pathway in lung adenocarcinoma

Jiang

Zhang

et al. 2021

Cell Biosci

View full text Add to dashboard Cite

show abstract

“…One of the first gene-expression-based models developed to predict outcomes after radiotherapy is the radiosensitivity index (RSI), which is based on the expression of 10 genes measured by microarray [ 45 ]. The RSI was developed from cell line data and was later validated in a variety of clinical cohorts [ 46 ]. The RSI has been combined with the linear quadratic model to derive the genomic-adjusted radiation dose (GARD) [ 47 ].…”

Section: Opportunities and Challenges For Precision Radiation Oncologymentioning

confidence: 99%

Liquid Biopsies for Molecular Biology-Based Radiotherapy

Blomain

Moding

2021

IJMS

View full text Add to dashboard Cite

Molecular alterations drive cancer initiation and evolution during development and in response to therapy. Radiotherapy is one of the most commonly employed cancer treatment modalities, but radiobiologic approaches for personalizing therapy based on tumor biology and individual risks remain to be defined. In recent years, analysis of circulating nucleic acids has emerged as a non-invasive approach to leverage tumor molecular abnormalities as biomarkers of prognosis and treatment response. Here, we evaluate the roles of circulating tumor DNA and related analyses as powerful tools for precision radiotherapy. We highlight emerging work advancing liquid biopsies beyond biomarker studies into translational research investigating tumor clonal evolution and acquired resistance.

show abstract

“…Based on the expression of 10 genes (JUN, STAT1, SUMO1, IRF1, HDAC9, ABL1, CDK1, RELA, PRRT2, and AR), RSI could predict intrinsic radiotherapy sensitivity and treatment response [ 3 ]. This model is widely used in cancer, such as breast cancer and NSCLCs [ 4 – 6 ].…”

Section: Introductionmentioning

confidence: 99%

Multiomics Differences in Lung Squamous Cell Carcinoma Patients with High Radiosensitivity Index Compared with Those with Low Radiosensitivity Index

Yuan

Zhuang

et al. 2021

Disease Markers

View full text Add to dashboard Cite

Objectives. Radiosensitivity Index (RSI) can predict intrinsic radiotherapy sensitivity. We analyzed multiomics characteristics in lung squamous cell carcinoma between high and low RSI groups, which may help understand the underlying molecular mechanism of radiosensitivity and guide optional treatment for patients in the future. Methods. The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) data were used to download clinical data, mRNA, microRNA, and lncRNA expression. Differential analyses, including mRNA, miRNA, lncRNA, and G.O. and KEGG, and GSVA analyses, were performed with R. Gene set enrichment analysis was done by GSEA. miRNA-differentially expressed gene network and ceRNA network were analyzed and graphed by the Cytoscape software. Results. In TCGA data, 542 patients were obtained, including 171 in the low RSI group (LRSI) and 371 in the high RSI group (HRSI). In RNAseq, 558 significantly differentially expressed genes (DEGs) were obtained. KRT6A was the most significantly upregulated gene and IDO1 was the most significantly downregulated gene. In miRNAseq, miR-1269a was the most significantly upregulated. In lncRNAseq, LINC01871 was the most upregulated. A 66-pair interaction between differentially expressed genes and miRNAs and an 11-pair interaction between differential lncRNAs and miRNAs consisted of a ceRNA network, of which miR-184 and miR-490-3p were located in the center. In the GEO data, there were 40 DEGs. A total of 17 genes were founded in both databases, such as ADAM23, AHNAK2, BST2, COL11A1, CXCL13, FBN2, IFI27, IFI44L, MAGEA6, and PTGR1. GSVA analysis revealed 31 significant pathways. GSEA found 87 gene sets enriched in HRSI and 91 gene sets in LRSI. G.O. and KEGG of RNA expression levels revealed that these genes were most enriched in T cell activation and cytokine−cytokine receptor interaction. Conclusions. Patients with lung squamous cell carcinoma have different multiomics characteristics between two groups. These differences may have an essential significance with radiotherapy effect.

show abstract

Precision radiotherapy for non-small cell lung cancer

Cited by 47 publications

References 124 publications

RRM2 silencing suppresses malignant phenotype and enhances radiosensitivity via activating cGAS/STING signaling pathway in lung adenocarcinoma

RRM2 silencing suppresses malignant phenotype and enhances radiosensitivity via activating cGAS/STING signaling pathway in lung adenocarcinoma

Liquid Biopsies for Molecular Biology-Based Radiotherapy

Multiomics Differences in Lung Squamous Cell Carcinoma Patients with High Radiosensitivity Index Compared with Those with Low Radiosensitivity Index

Contact Info

Product

Resources

About