BDNF, COMT, and DRD2 polymorphisms and ability to return to work in adult patients with low- and high-grade glioma

Altshuler, David; Wang, Lin; Zhao, Lili; Miklja, Zachary; Linzey, Joey; Brezzell, Amanda; Kakaizada, Sofia; Krishna, Saritha; Orringer, Daniel A.; Briceño, Emily M.; Gabel, Nicolette; Hervey-Jumper, Shawn L.

doi:10.1093/nop/npy059

Cited by 20 publications

(14 citation statements)

References 41 publications

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“…Our results compare well with previously published literature. Altshuler et al studied the association of genetic alterations with neurocognitive function and ability to return to work in a series of 34 patients with gliomas WHO grades II and III who did not receive adjuvant treatment following surgery [40]. Here, 42% of the patients returned to work within three months following surgery.…”

Section: Discussionmentioning

confidence: 99%

The ability to return to work: a patient-centered outcome parameter following glioma surgery

et al. 2020

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Background With refinements in diagnosis and therapy of gliomas, the importance of survival time as the sole outcome parameter has decreased, and patient-centered outcome parameters have gained interest. Pursuing a profession is an indispensable component of human happiness. The aim of this study was to analyze the professional outcomes besides their neuro-oncological and functional evaluation after surgery for gliomas in eloquent areas. Methods We assessed neuro-oncological and functional outcomes of patients with gliomas WHO grades II and III undergoing surgery between 2012 and 2018. All patients underwent routine follow-up and adjuvant treatment. Treatment and survival parameters were collected prospectively. Repercussions of the disease on the patients’ professional status, socio-economic situation, and neurocognitive function were evaluated retrospectively with questionnaires. Results We analyzed data of 58 patients with gliomas (WHO II: 9; III: 49). Median patient age was 35.8 years (range 21–63 years). Awake surgery techniques were applied in 32 patients (55.2%). Gross total and subtotal tumor resections were achieved in 33 (56.9%) and 17 (29.3%) patients, respectively, whereas in 8 patients (13.8%) resection had to remain partial. Most patients (n = 46; 79.3%) received adjuvant treatment. Median follow up was 43.8 months (range 11–82 months). After treatment 41 patients (70.7%) were able to resume a working life. Median time until returning to work was 8.0 months (range 0.2–22.0 months). To be younger than 40 at the time of the surgery was associated with a higher probability to return to work (p < .001). Multivariable regression analysis showed that patient age < 40 years as well as occupational group and self-reported fatigue were factors independently associated with the ability to return to work. Conclusion The ability to resume professional activities following brain tumor surgery is an important patient-oriented outcome parameter. We found that the majority of patients with gliomas were able to return to work following surgical and adjuvant treatment. Preservation of neurological function is of utmost relevance for individual patients´ quality of life.

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Section: Discussionmentioning

confidence: 99%

The ability to return to work: a patient-centered outcome parameter following glioma surgery

et al. 2020

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“…Studies have indicated that COMT can upregulate tumor suppressor genes by the PI3K/Akt pathway and inhibit the growth and invasion of cancer cells (31). COMT mutations are significantly correlated with cognitive impairment in brain tumor patients (32), and this conclusion is also applicable in glioma patients (33). Therefore, COMT may have a potential protective effect, and mutations in this gene may influence prognosis by affecting cognitive ability.…”

Section: Discussionmentioning

confidence: 96%

Prognostic prediction model for glioblastoma: a metabolic gene signature and independent external validation

Lei

Chen

Wang

et al. 2020

Preprint

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Background. Glioblastoma (GBM) is the most common primary malignant intracranial tumor and is closely related to metabolic alterations. However, few accepted prognostic models are currently available, especially models based on metabolic genes. Methods . Transcriptome data were obtained for all patients diagnosed with GBM from the Gene Expression Omnibus (GEO) (training cohort, n=369) and The Cancer Genome Atlas (TCGA) (validation cohort, n=152) with the following variables: age at diagnosis, sex, follow-up and overall survival (OS). Metabolic genes according to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were filtered, and a Lasso regression model was constructed. Survival was assessed by univariate or multivariate Cox proportional hazards regression and Kaplan-Meier analysis, and we also conducted an independent external validation to examine the model. Results. There were 341 metabolic genes that showed significant differences between normal brain tissues and GBM tissues in both the training and validation cohorts, among which 56 genes were significantly correlated with the OS of patients. Lasso regression revealed that the metabolic prognostic model was composed of 18 genes, including COX10 , COMT , and GPX2 , with protective effects, as well as OCRL and RRM2 , with unfavorable effects. Patients classified as high-risk by the risk score from this model had markedly shorter OS than low-risk patients ( P <0.0001), and this significant result was also observed in the independent external validation cohort ( P <0.001). Conclusions . The prognosis of GBM was dramatically related to metabolic pathways, and our metabolic prognostic model had high accuracy and application value in predicting the OS of GBM patients. Background. Glioblastoma (GBM) is the most common primary malignant intracranial tumor and is closely related to metabolic alterations. However, few accepted prognostic models are currently available, especially models based on metabolic genes. Methods . Transcriptome data were obtained for all patients diagnosed with GBM from the Gene Expression Omnibus (GEO) (training cohort, n=369) and The Cancer Genome Atlas (TCGA) (validation cohort, n=152) with the following variables: age at diagnosis, sex, follow-up and overall survival (OS). Metabolic genes according to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were filtered, and a Lasso regression model was constructed. Survival was assessed by univariate or multivariate Cox proportional hazards regression and Kaplan-Meier analysis, and we also conducted an independent external validation to examine the model. Results. There were 341 metabolic genes that showed significant differences between normal brain tissues and GBM tissues in both the training and validation cohorts, among which 56 genes were significantly correlated with the OS of patients. Lasso regression revealed that the metabolic prognostic model was composed of 18 genes, including COX10 , COMT , and GPX2 , with protective effects, as well as OCRL and RRM2 , with unfavorable effects. Patients classified as high-risk by the risk score from this model had markedly shorter OS than low-risk patients ( P <0.0001), and this significant result was also observed in the independent external validation cohort ( P <0.001).Conclusions . The prognosis of GBM was dramatically related to metabolic pathways, and our metabolic prognostic model had high accuracy and application value in predicting the OS of GBM patients.

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“…In an earlier study we discussed the notion of cognitive functioning as a marker for diffuse tumor infiltration, and the option that cognitive functioning and survival are determined by overlapping germline and somatic molecular-genetic factors. 3 Indeed, several studies already showed that multiple SNPs (single nucleotide polymorphisms) are associated with neurocognitive performance 26 , 27 and cognitive impairment is found to occur more frequently in glioma patients with wild-type IDH1 tumor status when compared to those with a mutant IDH1 tumor status. 28 , 29 A more recent publication of Daniel et.…”

Section: Discussionmentioning

confidence: 99%

Complications, compliance, and undertreatment do not explain the relationship between cognition and survival in diffuse glioma patients

Kessel

Krijnen

IJpelaar

et al. 2022

Neuro-Oncology Practice

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Background Cognitive deficits occur in all different grades of glioma. In a recent study, we found these deficits to be independently, and possibly causally, related to survival in diffuse gliomas. In this study, we investigated whether the relationship between cognition and survival was mediated by three different factors: undertreatment, complications of treatment, and compliance. We hypothesized that patients with cognitive impairment may undergo less intensive treatment, be less compliant and suffer more from complications, resulting in shortened survival for cognitively impaired patients. Methods In a retrospective cohort study of patients undergoing awake craniotomy between 2010 and 2019 we performed pre-operative neuropsychological assessments in five cognitive domains. We used Structural Equation Modelling to perform mediation analyses. Mediation analyses are analyses to evaluate whether a variable is a factor in the causal chain, referred to as an intermediate factor. Results In total 254 patients were included, of whom 111 patients were LGG patients and 143 were HGG patients. The most frequently impaired domain was memory (37.8% ≤-2 SD) in HGG and attention and executive functioning in LGG (33.3≤-1.5 SD). We confirmed the significant association between different cognitive domains and survival. This associations could not be explained by one of the aforementioned intermediate factors. Conclusions This suggests that other mechanisms should be involved in the relation between cognition and survival. Hypothetically, cognitive functioning can act as a marker for diffuse infiltration of the tumor or cognitive functioning and survival could be determined by overlapping germline and somatic tumoral molecular-genetic factors.

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BDNF, COMT, and DRD2 polymorphisms and ability to return to work in adult patients with low- and high-grade glioma

Cited by 20 publications

References 41 publications

The ability to return to work: a patient-centered outcome parameter following glioma surgery

The ability to return to work: a patient-centered outcome parameter following glioma surgery

Prognostic prediction model for glioblastoma: a metabolic gene signature and independent external validation

Complications, compliance, and undertreatment do not explain the relationship between cognition and survival in diffuse glioma patients

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