Darmawi

BHLHE22 Expression Is Associated with a Proinflammatory Immune Microenvironment and Confers a Favorable Prognosis in Endometrial Cancer

Endometrial cancer (EC) rates are rising annually. Additional prediction markers need to be evaluated because only 10–20% of EC cases show an objective response to immune-checkpoint inhibitors (ICIs). Our previous methylomic study found that BHLHE22 is hypermethylated in EC tissues and can be detected using a Pap-smear sample. BHLHE22, a basic helix loop helix transcription factor family member, is known as a transcriptional repressor and is involved in cell differentiation. However, the role of BHLHE22 in EC remains poorly understood. Herein, we analyzed BHLHE22 expression in 54 paired cancer and normal endometrial tissue samples, and confirmed with databases (TCGA, GTEx, and human protein atlas). We found that BHLHE22 protein expression was significantly downregulated in EC compared with normal endometrium. High BHLHE22 expression was associated with microsatellite-instable subtype, endometrioid type, grade, and age. It showed a significant favorable survival. BHLHE22 overexpression inhibited the proliferation and migration of EC cells. Functional enrichment analysis showed that BHLHE22 was significantly associated with immune-related pathways. Furthermore, BHLHE22 was positively correlated with proinflammatory leukocyte infiltration and expression of chemokine genes in EC. In conclusion, BHLHE22 regulates immune-related pathways and modulates the immune microenvironment of EC.

Promising candidate drug target genes for repurposing in cervical cancer: A bioinformatics-based approach

Cervical cancer is the fourth most common cancer among women globally, and studies have shown that genetic variants play a significant role in its development. A variety of germline and somatic mutations are associated with cervical cancer. However, genomic data derived from these mutations have not been extensively utilized for the development of repurposed drugs for cervical cancer. The objective of this study was to identify novel potential drugs that could be repurposed for cervical cancer treatment through a bioinformatics approach. A comprehensive genomic and bioinformatics database integration strategy was employed to identify potential drug target genes for cervical cancer. Using the GWAS and PheWAS databases, a total of 232 genes associated with cervical cancer were identified. These pharmacological target genes were further refined by applying a biological threshold of six functional annotations. The drug target genes were then cross-referenced with cancer treatment candidates using the DrugBank database. Among the identified genes, LTA, TNFRSF1A, PRKCZ, PDE4B, and PARP were highlighted as promising targets for repurposed drugs. Notably, these five target genes overlapped with 12 drugs that could potentially be repurposed for cervical cancer treatment. Among these, talazoparib, a potent PARP inhibitor, emerged as a particularly promising candidate. Talazoparib is currently being investigated for safety and tolerability in other cancers but has not yet been studied in the context of cervical cancer. Further clinical trials are necessary to validate this finding and explore its potential as a repurposed drug for cervical cancer.