Novel insights into the progression and prognosis of the calpain family members in hepatocellular carcinoma: a comprehensive integrated analysis.

Objectives: The goal of our bioinformatics study was to comprehensively analyze the association between the whole calpain family members and the progression and prognosis of hepatocellular carcinoma (HCC). Methods: The data were collected from The Cancer Genome Atlas (TCGA). The landscape of the gene expression, copy number variation (CNV), mutation, and DNA methylation of calpain members were analyzed. Clustering analysis was performed to stratify the calpain-related groups. The least absolute shrinkage and selection operator (LASSO)-based Cox model was used to select hub survival genes. Results: We found 14 out of 16 calpain members expressed differently between tumor and normal tissues of HCC. The clustering analyses revealed high- and low-risk calpain groups which had prognostic difference. We found the high-risk calpain group had higher B cell infiltration and higher expression of immune checkpoint genes HAVCR2, PDCD1, and TIGHT. The CMap analysis found that the histone deacetylase (HDAC) inhibitor trichostatin A and the PI3K-AKT-mTOR pathway inhibitors LY-294002 and wortmannin might have a therapeutic effect on the high-risk calpain group. The DEGs between calpain groups were identified. Subsequent univariate Cox analysis of each DEG and LASSO-based Cox model obtained a calpain-related prognostic signature. The risk score model of this signature showed good ability to predict the overall survival of HCC patients in TCGA datasets and external validation datasets from the Gene Expression Omnibus database and the International Cancer Genome Consortium database. Conclusion: We found that calpain family members were associated with the progression, prognosis, and drug response of HCC. Our results require further studies to confirm.

Axillary response and outcome in breast cancer patients after neoadjuvant treatment: The role of radiotherapy in reducing recurrence in ypN0 patients with initially cN+ stage.

Objective: We aim to explore the clinicopathological features associated with axillary node response and recurrence in breast cancer patients undergoing neoadjuvant treatment (NAT). Methods: We retrospectively reviewed the medical records of 486 stage I to III breast cancer patients who received NAT and surgery between 2016 and 2021. Results: A total of 486 cases were reviewed and 154 (31.7%) patients achieved breast pathological complete response (pCR) (ypT0/Tis). Of the 366 cases with initially cN+, 177 (48.4%) cases reach ypN0. Breast pCR is in high accordance to axillary pCR (81.5%). Hormone receptor (HR)-/HER2+ breast cancer patients have the highest axillary pCR rate (78.3%). Patients achieve axillary pCR have a significantly better disease-free survival (DFS) (P=0.0004). Further analysis reveals that the DFS of ypN0 and ypN1 cases are similar (P=0.9049). Moreover, DFS in patients with ypN0 (P<0.0001) and ypN1 (P<0.0001) is significantly better than that in patients with ypN2-3. For post-mastectomy ypN0 cases, radiation could only improve DFS in patients with initially cN+ stage (P=0.0499). Multivariate Cox regression analysis shows that radiation is an independent factor to improve DFS (Hazard ratio (HR): 0.288(0.098-0.841), P=0.0230). Radiation does not improve DFS in pre-cN0/ypN0 patients (P=0.1696). Conclusion: Axillary pCR rate is higher than breast pCR rate. HR-/HER2+ patients have the highest axillary pCR rate. Axillary pCR is associated with better DFS. Radiation could further improve DFS in ypN0 patients with initially positive nodal disease.