There are sex-dependent differences in gene expression between subtypes of diffuse large B-cell lymphoma (DLBCL), a new study published in Cancers found. There are also age-dependent differences between premenopausal and postmenopausal women, which may be due to estrogen. “This may contribute to the sex differences in incidence and prognosis,” the authors of the study wrote.

Like in many cancer types, the incidence and prognosis of lymphomas, including DLBCL, are more favorable in women than men, the reason for which is unclear.

Read more about the prognosis of DLBCL

In the present study, a team of researchers led by Sam Okret, MD, PhD, of the Department of Biosciences and Nutrition at Karolinska Institutet in Huddinge, Sweden, analyzed gene expression data from 746 samples of DLBCL, the most common type of lymphoma.

The results showed that there were 1293 genes that were differentially expressed between men and women. 

Some autosomal genes and pathways showed common sex-regulated expression between germinal center B-cell and activated B-cell DLBCL. 

When they analyzed differentially expressed genes in pre and postmenopausal women, the researchers found that 208 germinal center B-cell and 345 activated B-cell genes were differentially expressed. Of these, only 5 were shared. 

When they combined the differentially expressed genes between men and women and between premenopausalo and postmenopausal women, the researchers identified 9 putative estrogen-regulated genes in activated B-cell DLBCL. Of these, NR4A2, which has been reported as a tumor suppressor gene in lymphoma, showed induced expression, while MUC5B, the expression of which leads to a more malignant phenotype in many cancers, showed repressed expression. 

“We show that [activated B-cell] DLBCL females with a high NR4A2 expression showed better survival,” the researchers wrote. They confirmed that NR4A2 and MUC5B were regulated by estrogen by grafting an activated B-cell DLBCL cell line to mice. 

“Thus, estrogens may contribute to the sex and female age differences in incidence and prognosis observed,” they concluded.


Huang D, Berglund M, Damdimopoulos A, et al. Sex- and female age-dependent differences in gene expression in diffuse large B-cell lymphoma—possible estrogen effects. Cancers (Basel). Published online February 17, 2023. doi:10.3390/cancers15041298