Molecular features unique to glioblastoma radiation resistant residual cells may affect patient outcome - a short
Ekjot Kaur1,2, Jayant S Goda2,3, Atanu Ghorai1,2
1Shilpee Dutt Laboratory, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra, 410210, India.
Purpose:
Previously we have shown, using a primary glioblastoma (GBM) cell model, that a subpopulation of innately radiation resistant (RR) GBM cells survive radiotherapy and form multinucleated and giant cells (MNGCs) by homotypic fusions. We also showed that MNGCs may cause relapse. Here, we set out to explore whether molecular characteristics of RR cells captured from patient-derived primary GBM cultures bear clinical relevance.
Methods:
Primary cultures were derived from 19 naive GBM tumor samples. RR cells generated from these cultures were characterized using various cell biological assays. We also collected clinicopathological data of the 19 patients and assessed associations with RR variables using Spearman's correlation test and with patient survival using Kaplan-Meier analysis. Significance was determined using a log-rank test.
Results:
We found that SF2 (surviving fraction 2) values (p = 0.029), days of RR cell formation (p = 0.019) and percentage of giant cells (p = 0.034) in the RR population independently correlated with a poor patient survival. We also found that low ATM (Ataxia-telangiectasia mutated) expression levels in RR cells showed a significant (p = 0.002) negative correlation with SF2 values. A low ATM expression level in RR cells along with a high tumor volume was also found to negatively correlate with patient survival (p = 0.011). Finally, we found that the ATM expression levels in RR cells independently correlated with a poor patient survival (p = 0.014).
Conclusions:
Our data indicate that molecular features of innately radiation resistant GBM cells independently correlate with clinical outcome. Our study also highlights the relevance of using patient-derived primary GBM cultures for the characterization of RR cells that are otherwise inaccessible for analysis.
Insights
Radiation resistant glioblastoma cells with specific molecular features, like low ATM expression, correlate with poor patient survival. Patient-derived cultures are crucial for studying these cells and their clinical relevance.
Area of Science:
- Oncology
- Radiation Biology
- Genetics
Background:
- Glioblastoma (GBM) is an aggressive brain tumor.
- A subpopulation of radiation-resistant (RR) GBM cells can survive radiotherapy and form multinucleated giant cells (MNGCs), potentially leading to tumor relapse.
Purpose of the Study:
- To investigate the clinical relevance of molecular characteristics of innately radiation-resistant GBM cells.
- To determine if molecular features of RR GBM cells derived from patient cultures correlate with patient survival.
Main Methods:
- Primary GBM cultures were established from 19 patient tumor samples.
- Radiation-resistant (RR) cells were generated and characterized using cell biological assays.
- Clinicopathological data were collected, and associations with RR variables and patient survival were analyzed using Spearman's correlation, Kaplan-Meier analysis, and log-rank tests.
Main Results:
- SF2 values, days of RR cell formation, and percentage of giant cells in RR populations independently correlated with poor patient survival.
- Low ATM (Ataxia-telangiectasia mutated) expression in RR cells negatively correlated with SF2 values and independently correlated with poor patient survival.
- Low ATM expression combined with high tumor volume also negatively correlated with patient survival.
Conclusions:
- Molecular features of innately radiation-resistant GBM cells are independent predictors of clinical outcome.
- Patient-derived primary GBM cultures are valuable for characterizing RR cells, which are otherwise difficult to analyze.
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