Songjie Shen

Certain circular RNAs (circRNAs) are selectively enriched in extracellular vesicles (EVs), in which they contribute to intercellular communication and represent promising biomarkers, yet the sequence determinants of their sorting remain unclear. Existing computational predictors are optimized mainly for linear RNAs and rarely address circRNA localization into EVs. Here we introduce circExor, the first framework specifically designed for circRNA EV localization. We curate a dedicated benchmark data set of 2102 circRNAs and implement a variable-length end-to-end concatenation strategy together with k -mer frequency encoding to accommodate circular topology, long sequence length, and length heterogeneity. Using a tree-based classifier, circExor achieves superior performance compared with RNAlocate-v3 and ExoGRU, reaching an AUROC of 0.743 on the internal test set and an average AUROC of 0.680 on the held-out test set. SHAP-based analysis, sequence perturbation analysis, motif mapping, and cell-based experimental validation support the predicted EV tendency and identify YBX1, HNRNPK, HNRNPL, and NOVA2 as candidate RBPs potentially associated with circRNA sorting. CircExor therefore provides a predictive and interpretable framework that links in silico modeling to mechanistic hypotheses, and supports biomarker discovery and candidate prioritization for downstream studies of EV-associated circRNAs.

Background: Although triple-negative breast cancer (TNBC) patients commonly receive adjuvant chemotherapy after surgery, their prognoses vary. This study aimed to investigate how the intrinsic subtypes of TNBCs and immune status of patients affect their prognosis. Methods: A total of 111 TNBC patients were retrospectively analyzed at Peking Union Medical College Hospital from 2002 to 2014. All underwent surgery and received adjuvant chemotherapy per NCCN guidelines. Intrinsic subtypes (luminal A, luminal B, HER2-enriched, and basal-like) were identified using PAM50 profiling. Recurrence-of-risk (ROR) scores were classified into high, intermediate, and low. Immune status was assessed via a 17-gene panel and categorized as immune-strong or immune-weak. Statistical analyses included chi-square tests, Kaplan–Meier curves, log-rank tests, and Cox regression. Results: All four PAM50 subtypes were present, with basal-like being the most common (77%). Luminal A patients with low-to-intermediate ROR scores showed worse outcomes than other subtypes (DFS, p = 0.123; OS, p = 0.170). Unexpectedly, high-ROR patients had the longest DFS (p = 0.042). Immune-strong status correlated with improved DFS and OS in stage IIB–III patients (DFS, p = 0.029; OS, p = 0.003), and was associated with higher TILs (p = 0.015) and PD-L1 expression on tumor cells (p = 0.022). Conclusions: Multigene-based assessment of molecular subtype and immune status provides important prognostic insight into TNBC and may guide adjuvant treatment decisions, particularly in non-basal-like subtypes.

The purpose of this study was to establish two preoperative nomogram models to evaluate the status of axillary lymph nodes (ALNs) in early breast cancer pa

Background: The standard adjuvant chemotherapy for early‐stage, high‐risk breast cancer includes anthracyclines and taxanes. While anthracycline‐based regimens have proven effective in human epidermal growth factor receptor 2 (HER2)‐positive breast cancer, their efficacy may be reduced in HER2‐negative patients due to the lack of co‐amplification of DNA topoisomerase IIα, the primary target of anthracyclines. This study compared the efficacy and safety of the regimen of docetaxel, anthracycline, and cyclophosphamide (TAC) versus a novel regimen consisting of docetaxel, cyclophosphamide, and capecitabine (TCX), hypothesizing that replacement of anthracycline with capecitabine could offer superior outcomes in this patient population. Methods: In this open‐label, randomized controlled trial, 204 patients with pT1‐3, node‐positive or high‐risk node‐negative, HER2‐negative early‐stage breast cancer were enrolled between May 2011 and December 2013 (ClinicalTrials.gov: NCT01354522). Patients were randomized 2:1 to TAC ( n = 136) or TCX ( n = 68), with treatment administered every 21 days for six cycles. The primary endpoints were disease‐free survival (DFS) and overall survival (OS); secondary endpoints included distant disease‐free survival (DDFS), disease‐specific survival (DSS), and adverse event (AE) rates. Results: With a median follow‐up of 124.4 (range, 19.5‐147.8) months, TCX did not significantly improve the 10‐year DFS rate over TAC (71.5% ± 5.6% vs. 67.6% ± 4.0%, P = 0.477). However, the 10‐year OS rate was significantly higher in the TCX group than in the TAC group (91.0% ± 3.5% vs. 77.2% ± 3.6%, P = 0.009). The TCX group also showed trends toward improved 10‐year DDFS rate (82.0% ± 4.7% vs. 69.8% ± 3.9%, P = 0.052) and significantly higher 10‐year DSS rate (93.9% ± 3.0% vs. 77.8% ± 3.6%, P = 0.002) compared to the TAC group. Grade 3‐4 AEs occurred significantly more often in the TAC group than the TCX group (67.7% vs. 42.7%, P = 0.001). Conclusion: TCX may provide superior long‐term survival and a more favorable safety profile compared to TAC for patients with high‐risk HER2‐negative breast cancer, warranting further investigation in larger cohorts.

Calreticulin (CALR) preserves reticular homeostasis by maintaining correct protein folding within the endoplasmic reticulum. Immunogenic cell death (ICD) is a regulated form of cell death and could activate adaptive immune response. As one of the damage-associated molecular patterns during ICD process, surface-exposed CALR resulted in the activation of adaptive immune response. Here, we evaluated the expression patterns of CALR in a cohort of 231 untreated triple-negative breast cancer (TNBC) and determined correlations between CALR expression and clinicopathologic parameters, programmed cell death ligand 1 (PD-L1) expression in immune cells (ICs), and survival. In addition, we analyzed a TNBC data set from The Cancer Genome Atlas to explore the relationship between mRNA expression of CALR and clinicopathologic features, IC infiltration, and survival. Tissue microarray results showed that high CLAR was strongly correlated with advanced stage (P = 0.022), shorter disease-free survival (P = 0.008) and overall survival (P = 0.002), and independently predicted prognosis in TNBC. Spearman analyses demonstrated that CALR negatively correlated with PD-L1 in ICs (r = -0.198, P = 0.003). Patients with low CALR and high PD-L1 in ICs had the best disease-free survival (P = 0.013) and overall survival (P = 0.004) compared with other patients, especially the patients with high CALR and low PD-L1 in ICs. In the “The Cancer Genome Atlas” cohort, CALR mRNA expression in tumors was significantly higher than that in normal tissues (P < 0.001). CALR expression was strongly and positively related to other ICD-related genes. These findings demonstrated that the expression of CALR could independently predict the prognosis in patients with TNBC, and it may play a potential synergistic role in treatments involving immunotherapy.

Breast cancer remains the most prevalent cancer among women globally, with significant links to obesity and lipid metabolism abnormalities. This review examines the role of lipid metabolism in breast cancer progression, highlighting its multifaceted contributions to tumor biology. We discuss key metabolic processes, including fatty acid metabolism, triglyceride metabolism, phospholipid metabolism, and cholesterol metabolism, detailing the reprogramming that occurs in these pathways within breast cancer cells. Alterations in lipid metabolism are emphasized for their roles in supporting energy production, membrane biogenesis, and tumor aggressiveness. Furthermore, we examine how lipid metabolism influences immune responses in the tumor microenvironment, affecting immune cell function and therapeutic efficacy. The potential of lipid metabolism as a target for novel therapeutic strategies is also addressed, with a focus on inhibitors of key metabolic enzymes. By integrating lipid metabolism with breast cancer research, this review underscores the importance of lipid metabolism in understanding breast cancer biology and developing treatment approaches aimed at improving patient outcomes.

Background Intraductal papillary neoplasms (IPNs) often have a similar clinical and imaging presentation, making them difficult to diagnose. We designed this study to refine and compare intraductal papillary neoplasms' clinical and imaging characteristics. Methods This study included a total of 154 patients with a postoperative diagnosis of IPNs and collected their clinical, imaging, and pathological data. We compared the clinical and imaging characteristics of benign, atypical hyperplasia, and malignant lesions. We also compared the diagnostic efficacy of ultrasound and mammography. Results The mean age of malignant patients was 57 years old, which was significantly higher than that in the other groups (48 years in the benign group and 47 years in the atypical hyperplasia group). The proportion of patients with malignant lesions clinically presenting as palpable masses (31.3%) was significantly higher than that of benign lesions (8.6%) (P < 0.05). The proportion of malignant lesions presenting in the periphery (≥ 3 cm from the nipple) was 40.6% compared to 22.4% for benign (P < 0.05). In ultrasonography, characteristics that showed statistically significant differences between benign and malignant lesions were the shape of the mass and calcification (P < 0.05). On mammography, differences were found in mass shape, calcification, and density of masses and glands (P < 0.05). Conclusions Clinical features such as age, symptoms, lesion location, and imaging characteristics such as shape, calcification, mass, and density may help to differentiate the classifications of IPNs. Trial registration: This study was registered at ClinicalTrials.gov on 12/06/2020 (identifier: NCT04429269).

Background: Breast cancer has become a critical international healthcare issue. Specifically, among the different subtypes, breast cancer marked by human epidermal growth factor receptor 2 (HER2)-overexpression usually correlates with low survival and a poor prognosis and poses challenges in treatment, thus leading to high mortality. Case Description: A 54-year-old female patient was diagnosed with a large T4cN2aM0 stage IIIB breast tumor with HER2 overexpression. The tumor size was large, and there was a lack of opportunity for surgery. However, after neoadjuvant chemotherapy (NACT), the size of the tumor continuously shrank, and the patient successfully underwent a modified radical mastectomy. Even though a certain amount of mass remained and she did not complete six courses of NACT, our patient’s postoperative pathological result still revealed that a pathological complete response (pCR) was achieved. The appropriate time window for choosing surgical intervention should be determined based on the patient’s general condition instead of complying with the treatment guidelines. Also, imaging findings may be misleading in patients who have undergone NACT. Moreover, the regimen should be chosen flexibly. Conclusions: Patients with locally advanced breast cancer can still achieve a radical surgical resection following appropriate comprehensive treatment. Hopefully, this case can provide new ideas for surgeons when they face similar conditions.

Myofibroblastic sarcoma is a malignancy in which myofibroblasts are the main component, with a very low incidence. In this study, we report a case of low-grade myofibroblastic sarcoma (LGMS) in the breast. After the diagnosis of LGMS, the patient received a mastectomy. The patient showed no relapse or progression during the follow-up time of 3 months following the operation. LGMS in the breast is extremely rare, and the limited experience with its diagnosis and treatment brings obstacles to doctors. Therefore, this report summarizes the preoperative diagnosis, treatment, and prognosis of breast LGMS through a literature review.