BRCA2 overexpression

Furthermore, we described that estrogen induces MLH1 expression through estrogen receptor alpha (ERα), which might explain why the majority of BRCA2 mutation carriers develop ER positive breast cancer. Taken together, our findings reveal a role of MLH1 in relieving replicative stress and how it may contribute to the establishment of BRCA2-deficient breast tumors.

We demonstrated that mutant P53 protein directly promoted FADS1 transcription, increasing ARA accumulation in HCC TME. FADS1 remodeling the metabolic patterns of PUFAs impaired CD8+CD103+Trm anti-tumor immunity, possibly leading to HCC progression.

Furthermore, BRCA1/2 may influence BRCA prognosis through catalytic activity, acting on DNA, chromosomal regions, organelle fission, and the cell cycle. Nevertheless, further validation is warranted.

Moreover, post-operative adjuvant chemotherapy could significantly affect DSS, regardless of PD-L1/PD-L2 expression status (positive or negative) on TCs, while it only prolonged DSS in PDL1-ICs (p < 0.0001) and PDL2-ICs (p < 0.0001) subgroups. This study provides a comprehensive understanding of the roles of PD-L1 and PD-L2 in PDAC, supporting anti-PD-1 axis immunotherapy for PDAC.

Targeting Siglec-15 may be a novel therapeutic option for patients who are unresponsive to anti-PD-1 therapy. Future studies are needed to validate the prognostic significance of Siglec-15 and to investigate its regulatory mechanisms in this disease.