Abstract Body: Cerebral aneurysms (CA) arise from the sites of weakened artery walls in the brain, and they may cause hemorrhagic stroke, coma, and death when they rupture. Studies have revealed sex differences in ~1.5 times higher prevalence of CA and ~1.5 times higher CA rupture rate in females. It is believed that mechanisms of CA formation in women may differ from those in men; however, sex-specific CA biomarkers are poorly identified. We hypothesized that sex-specific CA biomarkers can be identified through cross-comparison between sexes using transcriptomics. Here, we reanalyzed 100 RNAseq samples containing 62 unruptured CAs (20 males/42 females) and 38 normal (19/19) acquired from 3 datasets of 6 manuscripts published between 2016 and 2021 for sex-specific biomarker identification in unruptured CA. Reanalysis of ~40K differentially expressed genes (DEGs) of transcriptomes filtered 1,106 and 1,133 CA genes in males and females respectively under the cutoff set at a 2-fold difference with a significant difference at p<0.05 (Image 1A-B). 117 genes were conserved biomarkers for both sexes, and the remaining 989 and 1,016 genes were classified as sex-specific biomarkers of unruptured CA in males and females, respectively (Image 1C). In Gene Set Analysis (GSA), intriguingly, although the ribosome biogenesis in eukaryotes pathway (03008) was enriched in both sexes, rRNAs were highly expressed in females whereas snoRNAs were predominant in males. Besides, pathways linked to micro-/onco-immunity jumped out but were distinct in both sets of biomarkers (05165, 05146, 05203, 04151 & 04061 in females, 05150, 05206, 05205, 05202, 04060 & 04630 in males). REACTOME analysis also highlighted pathways associated with DNA integrity and repair (5693532, 69481, 69620, 69473, 5693538, 5693606, 5693565, 5693607 & 5693567) in females, and pathways related to antimicrobial immunity (6798695, 6803157, 5683057, 1462054, 1461973, 168256 & 168249) in males (Image 2). Finally, STRING functional protein analysis identified multiple hub genes including COLs (collagen) and WNTs (Wnt signaling) in females, and DEFAs (defensin), BPI (bactericidal permeability-increasing protein), and LCN2 (lipocalin, anti-bacterial innate immunity) in males, which aligns abovementioned pathways (Image 3). These analyses suggest that antimicrobial immunity is a risk factor for CA. Taken together, this study reveals sex-specific CA biomarkers and provides insights for sex-dependent pre-diagnosis for future studies.