4 | Discussion
This study aimed to assess the influence of gender and age on the occurrence and survival outcomes of glioblastoma multiforme (GBM). Analyzing a cohort of 164 GBM patients, the average age was 54, with higher prevalence in men (59.8%) and those aged 60 or younger (64.6%). The cohort’s mean survival was 12.88 ± 14.14 months, ranging from 0 days to 85 months, with a 45% estimated one-year survival rate. Women exhibited higher one-year survival (60% vs. 40%) and prolonged average survival (16.14 ± 17.35 vs. 10.75 ± 11.15 months). Patients aged 60 or younger had significantly higher one-year survival (75% vs. 35%). Moreover, Subgroup analysis revealed markedly higher survival rates for women aged 60 or younger (p < 0.045). Nonetheless, in individuals over 60, women experienced a more pronounced decline in survival rates, and no statistically significant difference was observed between males and females in this age category. (p = 0.56). The accelerated decline in survival among older women could be attributed to the potential protective role of gonadal steroid hormones in younger females, particularly estradiol, which significantly decreases during menopause24.
In line with our findings, prior research has consistently emphasized significant gender disparities in both the occurrence and prognosis of glioma, particularly in the context of glioblastoma25,26. Despite multiple investigations on this topic, the biological mechanisms responsible for these gender differences in GBM remain incompletely understood 27,28. For instance, a study conducted by Sun et al. 29 suggested that this gender gap might be partially attributed to a higher vulnerability to malignant transformation in male astrocytes when both the p53 and NF1 genes lose their normal functions in contrast to female astrocytes. Moreover, in a study by Khan et al. 30, researchers utilized data from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) to identify molecular markers that could elucidate gender-based differences. They discovered that specific autosomal genes such as NOX, FRG1BP, and AL354714.2, along with X-linked genes such as PUDP, KDM6A, DDX3X, and SYAP1, displayed varying DNA methylation and gene expression profiles in male and female GBM cases. Furthermore, high expression of estrogen-related receptor alpha (ERRα) is considered a detrimental factor associated with malignant progression and overall prognosis in various cancer types31–33. In contrast, Hönikl et al.’s study demonstrated that high expression of estrogen receptor alpha (Erα) and aromatase in 60 GBM tissue samples was associated with longer survival times, and treatment with high concentrations of estradiol resulted in reduced tumor cell viability34. Despite contradictory findings on estrogen receptor subtypes as prognostic factors, studies suggest a protective role of estradiol(E2), mainly through estrogen receptor beta (Erβ), with varying effects depending on ERβ isoform quantities28. While the estrogen-related pathway has been extensively researched in glioma, it has been challenging to translate this knowledge into practical clinical applications within standard treatment protocols 32.
In 2018, Minjie Tian et al.35 utilized the Surveillance, Epidemiology, and End-Results (SEER) database to study GBM patients undergoing surgery from 2000 to 2008. Of the 6,586 identified GBM patients, 65.5% were male, closely aligning with our findings. The study concluded that gender significantly predicts GBM risk. In a 2021 study by Osawa et al.36, they examined 137 GBM patients, with 22.6% being elderly (over 75 years old). Non-elderly patients had a significantly longer average overall survival (15.8 months) than the elderly group (10.8 months). Similarly, non-elderly patients had a significantly longer average progression-free survival (9.1 months) compared to the elderly group (6.6 months). The study suggested that, for patients aged 75 and older with a Karnofsky Performance Status (KPS) below 70, indicating diminished daily functional capacity, considering less aggressive treatment in addition to radical resection could be a viable therapeutic option. In 2015, Brodbelt et al.37 analyzed GBM patients’ data in England from 2007 to 2011, including 10,743 patients, with 6,451 males and 4,292 females. The average overall survival was 6.1 months, and survival rates at one, two, and five years were 28.4%, 11.5%, and 3.4%, respectively. Survival declined significantly with increasing age, from 16.2 months in the 20-44 age group to 3.2 months in those aged 70 and above. Among patients receiving maximum therapy, those under 70 years had an average survival of 14.9 months. While maximum therapy enhanced overall survival across all age groups, individuals aged over 60 were less inclined to receive complete combination therapy37. These age-related differences align with our findings, where 35.4% of GBM patients were over 60, experiencing notably shorter mean overall survival and a lower one-year survival rate compared to their younger counterparts. We performed a bibliometric analysis to highlight the current trends in research related to age and gender within the context of GBM. (Figure 6)