Tumours have a sex: impact on the response of bladder cancer and lung adenocarcinoma to therapy

Abstract

Background: The 23rd pair of chromosomes in humans is responsible for sex determination, in which humans are categorised as female (XX chromosomes) or male (XY chromosomes). While phenotypically, male and females are different, the sex chromosomes have been found to impact a wide variety of other factors such as disease susceptibility and the immune system. Sex has been an under researched variable in scientific research. To counter this, `Sex as a biological variable? (SABV) is a policy that strives for sex-inclusion at all stages of research. In cancer, there is considerable evidence that there are discrepancies in incidence and mortality rates based on sex. While bladder cancer is predominantly diagnosed in males, females have been frequently reported to have a poorer survival rate post-diagnosis. In lung cancer, males are diagnosed at a higher incidence than females. In non-smoking females, the rates of lung adenocarcinoma are significantly larger than in males, however males have worse survival outcome, indicating a sex-specific variable in the development and survival of lung adenocarcinoma.

Purpose: To characterise the link between the sex chromosomes and key sex-specific DNA damage genes and cellular senescence genes in bladder cancer and lung adenocarcinoma. Additionally to investigate specific X chromosomes response to radiation therapy and fisetin impacts in a sex-dependent manner.

Results: The discovery of a panel of sex chromosome genes in-silico in bladder cancer and lung adenocarcinoma. Two of these genes (CENPI and ERCC6L) were found to have sex-specific gene expression response to fisetin and radiation exposure in lung adenocarcinoma cell lines. Sex-specific DNA damage response gene expression in bladder cancer and lung adenocarcinoma were discovered.

Conclusion: There is increasing evidence that the sex-specific sex chromosome gene expression impacts on bladder cancer and lung adenocarcinoma and may be linked to pathways involved in cancer progression, such as DNA damage response pathways and cellular senescence pathways.