There are rarely systematic studies to analyze the prognostic factors among non-surgical liver cancer patients. Whether there is a gender difference in the survival of non-surgical liver cancer patients and what may cause this difference is still unclear.

A total of 12,312 non-surgical liver cancer patients were enrolled in this study. Age, race, sex, grade, tumor TNM stage, marital status, tumor size, and histological type were independent risk factors in liver cancer and were confirmed in the validation cohort. Before menopause, females demonstrated a better mean survival probability than males (39.4±1.4 vs. 32.7±0.8 months, respectively; p<0.001), and continued in post-menopause. The results of differentially expressed genes (DEGs) and KEGG pathway analysis showed that there were significant differences in steroid hormone biosynthesis between male and female liver cancer patients. In vitro experiments revealed that estradiol inhibited the proliferation of hepatocellular cancer cell lines and increased apoptosis, but estrone exerted no effect.

In conclusion, gender differences in prognosis among non-surgical liver cancer patients were confirmed and attributable primarily to estradiol.