ESTRO 2024 - Abstract Book

S5402

Radiobiology - Tumour biology

ESTRO 2024

Conclusion:

HMGB2 KD reduced the proportion of cells in G2/M phases of the cell cycle, which is in line with our correlative studies that showed positive correlation between high HMGB2 expression and mitotic counts in grade 4 astrocytomas. Importantly, HMGB2 KD reduced cell proliferation and slightly sensitized glioblastoma cells to radiation independent of TP53 status. Taken together, our histopathological and mechanistic results suggest that high HMGB2 expression is related to glioma progression by increasing cell proliferation. Further computational analysis suggests that HMGB2 is a downstream of the RB-E2F pathway, as it correlates with E2F expression and has E2F binding sites 6 , which may explain high expression in G2/M in our results. HMGB2 may be developed as an early biomarker of glioma evolution for lower grade IDHwt gliomas and as a potential target for drug development, tackling two of the main canonical pathways in glioma progression.

Keywords:

cell

proliferation,

TP53,

glioblastoma

References:

1. Becker A.P.; Becker V; McElroy, J.; Webb A.; Han C.; Guo Y.; Bell E.H.; Fleming J.; Popp, I.; Staszewski, O.; Prinz, M.; Otero, J.J.; Haque, S.J.; Grosu, A.L.; Chakravarti, A. Spatial heterogeneity proteomic analysis identifies HMGB2 as putative biomarker of tumor progression in adult-type diffuse astrocytomas. 2023 (in preparation). 2. Cancer Genome Atlas Research N. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008;455(7216):1061-8. Epub 20080904. doi: 10.1038/nature07385. PubMed PMID: 18772890; PMCID: PMC2671642.

3. Engeland K. Cell cycle regulation: p53-p21-RB signaling. Cell Death Differ. 2022;29(5):946-60. Epub 20220331. doi: 10.1038/s41418-022-00988-z. PubMed PMID: 35361964; PMCID: PMC9090780.

4. Wu ZB, Cai L, Lin SJ, Xiong ZK, Lu JL, Mao Y, Yao Y, Zhou LF. High-mobility group box 2 is associated with prognosis of glioblastoma by promoting cell viability, invasion, and chemotherapeutic resistance. Neuro Oncol. 2013;15(9):1264-75. Epub 20130704. doi: 10.1093/neuonc/not078. PubMed PMID: 23828241; PMCID: PMC3748920. 5. Shin YJ, Kim MS, Kim MS, Lee J, Kang M, Jeong JH. High-mobility group box 2 (HMGB2) modulates radioresponse and is downregulated by p53 in colorectal cancer cell. Cancer Biol Ther. 2013;14(3):213-21. Epub 20121219. doi: 10.4161/cbt.23292. PubMed PMID: 23255232; PMCID: PMC3595303. 6. Rouillard AD, Gundersen GW, Fernandez NF, Wang ZC, Monteiro CD, McDermott MG, Ma'ayan A. The harmonizome: a collection of processed datasets gathered to serve and mine knowledge about genes and proteins. Database-Oxford. 2016. doi: ARTN baw100 10.1093/database/baw100. PubMed PMID: WOS:000381520100001.

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Mini-Oral

Nuclear translocation of ROCK1 mediates Ku70 serine 477 phosphorylation in NHEJ and radiosensitivity