A study led by researchers at the Washington University School of Medicine has shed light on why more males than females develop and die from the deadly brain cancer, glioblastoma.
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The team identified distinct molecular signatures in tumors taken from men and women that helped to explain the disparity in treatment and survival rates.
The study suggests that tailoring treatments based on the molecular subtype of men and women’s tumors may improve patient outcome.
It is our expectation that this study could have an immediate impact on the care of patients with glioblastoma and further research. The findings indicate we should be stratifying male and female glioblastoma into risk groups and evaluating the effectiveness of treatment in a sex-specific manner."
Dr. Joshua Rubin, Co-senior Author
In a study of adults with glioblastoma, Dr. Joshua Rubin and colleagues found that women responded better to treatment than men.
To investigate why, they used standard MRI scans to measure tumor growth velocity, enabling them to derive a value for how quickly tumors were growing.
As reported in the journal Science Translational Medicine, the team then pulled patients’ MRI scan and survival data from a cancer research database and assessed tumor growth velocity every two months among 40 males and 23 females who received standard chemo-radiation therapy after they had undergone surgery.
"The males did not respond as well, and we wanted to understand why, so we looked at the underlying genetics of patients' tumors," says Rubin.
The researchers tapped into The Cancer Genome Atlas and applied advanced statistical algorithms that would distinguish male- or female-specific gene expression patterns from such patterns that were shared among the male and female patients.
They then looked at sex-specific gene expression to find molecular subtypes that would correspond with the differences seen in male and female survival.
Co-senior author Jingqin Luo says: "We observed tremendous genetic sex differences in the tumors of glioblastoma patients that correlated with survival."
The team found that tumors were clustered into five subtypes in males and five in females. Females with tumors from one cluster survived just over three years compared with just over one year among females with tumors from any of the other four clusters.
Similarly, men with tumors from one cluster survived just over 18 months compared with just over one year among men who had tumors from the other four clusters.
The team also identified genetic pathways that correlated with the longest survival and they were very different in males compared with females, says Rubin. For example, survival among males was partially dependent on the regulation of cell division, suggesting that medication to block the cell cycle may be more effective in men.
Among women, survival was affected by regulation of invasiveness, indicating that targeting integrin signaling may be the most effective approach.
This tells us it might be better to separate males and females and examine their sex-specific genetic signatures.”
Joshua Rubin, Co-senior Author
Sex differences identified in deadly brain tumors.