Women and men with early stage bladder cancer show strikingly different gene activity in their tumors, according to a study published recently in BMC Cancer.
The researchers reported that hundreds to thousands of genes behave differently depending on a patient’s sex, supporting the need for more personalized and sex-specific management of bladder cancer. This finding could one day change how doctors approach treatment and monitoring.
Bladder cancer is more common in men, yet women often face higher recurrence rates and worse outcomes. To better understand why, investigators analyzed tumor tissue and nearby healthy bladder lining from 51 patients with low-grade Ta stage non-muscle-invasive bladder cancer.
Of these, 22 were women and 30 were men. The mean age was 73 years for both sexes. There were no statistically significant differences between women and men in smoking status or tumor features such as size, number or whether the tumor was primary or recurrent.
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Using whole transcriptome sequencing, the team compared 49 tumor samples and 52 healthy bladder mucosa samples. In women, 2,391 protein coding genes had different expression levels between tumor and healthy tissue. In men, 5,640 genes differed. Among the top 100 most significant genes, 19% were more active in women’s tumors compared with healthy tissue, while 90% were more active in men’s tumors.
“Our findings suggest that sex-specific molecular mechanisms may contribute to BC [bladder cancer] biology and progression,” explained the authors of this study.
Some of the most altered genes in women included MT ND6, ARL4C, ASGR1, MYBL1 and SCAMP5. In men, the leading genes were ONECUT2, SPEG, CTSE, GJB2 and SYNM. Overall, 753 differentially expressed genes were unique to women, 3,989 were unique to men and 1,633 were shared.
When researchers looked at what these genes do, clear patterns emerged. In women, unique genes were strongly linked to immune-related pathways such as regulation of leukocyte activation, lymphocyte differentiation and cell-to-cell adhesion. In men, unique genes were more often tied to the cell cycle, mitochondrial function and androgen receptor signaling. Further immune analysis showed that women’s tumor-specific genes were connected to antigen receptor signaling and control of immune activation, while men’s were linked to B-cell activation and neutrophil-mediated immune responses.
A statistical interaction model identified S100A14 as the only protein coding gene with a clearly significant sex dependent expression pattern in tumors. Four additional genes (GJB2, DSC2, TM4SF1 and ALOX15B) showed probable interaction effects.
For patients, these findings suggest that the biology of their cancer may differ based on sex. In the future, this could influence which treatments are chosen, how closely patients are monitored and how new therapies are developed to improve outcomes for both women and men.
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