The researchers culled patient MRI scans and survival data from a cancer research database. They then calculated tumor growth velocity every two months for the duration of therapy in 63 glioblastoma patients — 40 males and 23 females — who received standard chemo-radiation treatment following surgery. While initial tumor growth velocities were similar between females and males, only the females showed a steady and significant decline in tumor growth after treatment with temozolomide, the most common chemotherapy drug used to treat glioblastoma.

“The males did not respond as well, and we wanted to understand why, so we looked at the underlying genetics of patients’ tumors,” said Rubin, a co-leader of the Solid Tumor Therapeutics Program at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.


The researchers tapped into The Cancer Genome Atlas (TCGA) — a project launched in 2005 to pursue the genetic basis of cancer and funded by the National Cancer Institute and National Human Genome Research Institute, both of the National Institutes of Health (NIH). Led by the study’s co-senior author Jingqin “Rosy” Luo, PhD, a Washington University associate professor of surgery in the Division of Public Health Sciences, and the study’s lead author, Wei “Will” Yang, PhD, a Washington University bioinformaticist in the Department of Genetics, the researchers applied sophisticated statistical algorithms to distinguish male- or female-specific gene expression patterns from such patterns that were shared among the male and female patients. The team then focused on the sex-specific gene expression to identify molecular subtypes that corresponded to differences in survival for males and for females.

“We observed tremendous genetic sex differences in the tumors of glioblastoma patients that correlated with survival,” Luo said. “All evidence supports the need to define these distinctions and incorporate the sex differences into glioblastoma biology research and treatment.”

Specifically, the researchers showed that the tumors of patients with glioblastoma cluster into 10 distinct subtypes — five for tumors in males and five for tumors in females. The clusters are distinguished by gene activity and survival. For example, females with tumors in one such cluster survived longer than females with tumors in any of the other four clusters — just over three years compared with just over one year. Similarly, they found a male cluster linked to longer survival — just over 18 months compared with just over one year for men with tumors in the other clusters.

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