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)