Bioprospecting potential genetic biomarkers of gallbladder cancer.

BACKGROUND

Gallbladder cancer (GBC) is a rare and aggressive cancer of the biliary tract with a very low survival rate. The availability of diagnostic biomarkers and targeted therapies for its management is limited. The study identifies potential genetic biomarkers of GBC by analyzing differentially expressed genes (DEGs) through microarray profiling and constructing regulatory networks using systems biology techniques.

METHODS

We used Clariom™ D Array in gallbladder cancer, cholelithiasis, and normal tissues (10 cases in each group), identifying DEGs and key biological pathways. Functional analysis via Metascape, DisGeNET, and KEGG-SIGNOR network mapping revealed gene-disease relationships and protein interactions.

RESULTS

There were 3,898 significant DEGs (|Fold Change| > 2.0, p < 0.05) identified in GBC compared to normal gallbladder tissue, with 2,575 genes upregulated and 1,323 downregulated. On comparison with cholelithiasis, 2523 DEGs (|Fold Change|>2.0, p < 0.05) were upregulated and 1451 downregulated. The functional analyses have shown that these DEGs were mainly involved in anatomical structure maturation and cell-cycle regulation. Top ten identified hub genes were XAB2, XPA, RPA1, RAD51B, RPS27A, BRCA2, ATR, PDS5B, CCNB2 and RANBP2. The top 3 related pathways were mismatch repair pathway, nucleotide excision repair and homologous recombination.

CONCLUSION

A significantly high differential gene expression was identified in gallbladder cancer compared to control groups. For the first time, we identified key genes-XAB2, XPA, RPA1, RAD51B, RPS27A, BRCA2, ATR, PDS5B, CCNB2, and RANBP2-as crucial players in homologous recombination, mismatch repair, DNA damage repair, and DNA replication processes that contribute to gallbladder carcinogenesis.