BRCA1 underexpression

BRCA1 expression is correlated with the prognostic value of platinum-based chemotherapy for stage II-IV NSCLC patients. In Caucasian population, compared with low BRCA1 expression, its high expression has a negative effect on the overall survival and event-free survival in stage II-IV NSCLC patients after platinum-based chemotherapy; however, this correlation was not found in China.

Unlike familial breast cancers with low BRCA1 mRNA expression, no significant correlation was observed between the loss of PTEN expression and low BRCA1 mRNA expression in this unselected TN tumours panel. Our data suggest that, unlike the germinal context, PTEN and BRCA1 alterations in sporadic TN breast tumours are independent events.

For the first time, this study elucidates the molecular signaling behind breast tumorigenesis involving BRCA1 hypermethylation. Like BRCA1 mutation screening, our findings open up an outstanding opportunity for screening sporadic breast cancers in females using the combination of NBR2, β-hCG, and BRCA1 hypermethylation as biomarkers from blood. Moreover, as therapeutic intervention, this study also provides scope for the use of BRCA1 hypermethylation reversing drugs like methotrexate, drugs like biguanides that show better action under NBR2 depleted conditions and development of β-hCG inhibitors for a better prognosis.

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.