Abstract
Senescence is a major response to cancer chemotherapy and has been linked to unfavorable therapy outcomes. Lamin B1 is a component of the nuclear lamina that plays a pivotal role in chromatin stability. Downregulation of lamin B1 represents an established biomarker for cellular senescence. However, the protein expression level of lamin B1 in malignant tissue, particularly of the breast, has not been previously described. In this work, we investigated lamin B1 protein expression in normal breast epithelium, malignant breast tissue (including adjacent non-malignant tissue) and in malignant tissue exposed to neoadjuvant chemotherapy (NAC) using immunohistochemistry (IHC) in three patient groups (n = 15, n = 87, and n = 43, respectively). Our results indicate that lamin B1 mean positive expression was 93% in normal breast epithelium and 88% in malignant breast cells, but significantly decreased (mean: 55%, p < 0.001) in malignant breast tissue after exposure to NAC, suggestive of senescence induction. No significant association between lamin B1 expression and other clinicopathological characteristics or survival of breast cancer patients was recorded. To our knowledge, this is the first report that established the baseline protein expression level of lamin B1 in normal and malignant breast tissue, and its reduction following exposure to chemotherapy. In conclusion, lamin B1 downregulation can be used reliably as a component of multiple biomarker batteries to identify therapy-induced senescence (TIS) in clinical cancer.
Highlights
Group B is comprised of 87 female patients (n = 87) diagnosed with primary invasive breast carcinoma whose tumors have not been exposed to neoadjuvant chemotherapy (NAC)
Collected postsurgically, while group C represents an independent sample of female patients (n = 43) diagnosed with invasive breast carcinoma whose samples were exposed to NAC preoperatively
We investigated the correlation between lamin B1 protein expression and the overall survival of breast tumor samples that were not exposed to NAC and ones that were post-NAC
Summary
Breast cancer is one of the most prevalent types of human malignancies, comprising. 30% of the estimated newly diagnosed female cancers in 2021 and the second leading cause of cancer-related deaths in women worldwide [1]. The overall survival rates for breast cancer have improved significantly due to the latest advances in early screening, molecular and pathologic diagnosis as well as the development of effective therapeutic modalities. Further efforts are needed to decrease the morbidity and mortality associated with breast cancer. The identification of novel drug targets and biomarkers that predict the outcome of currently available therapy is sought
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
