S100 calcium‐binding protein A (S100A) family members regulate multiple biological functions related to pancreatic cancer (PC) progression and metastasis. However, the prognostic and oncologic values of S100A family have not been systematically investigated in PC. In the present study, the mRNA expression and potential functions of S100A family were investigated by bioinformatic analysis. Our results demonstrated that overexpression of S100A2, S100A6, S100A10, S100A11, S100A14 and S100A16 was significantly associated with higher T stage, advanced histologic grade and worse prognosis in PC. Besides, one CpG of S100A2, three CpG of S100A6, four CpG of S100A10, four CpG of S100A11, two CpG of S100A14 and five CpG of S100A16 were negatively associated with corresponding S100A family members expression and positively associated with overall survival (OS). The signature based on four CpGs showed good prediction ability of OS. Besides, S100A2 overexpression took part in the regulation of mitotic cell cycle, ECM‐receptor interaction and HIF‐1α transcription factor network. Overexpression of S100A6, S100A10, S100A11, S100A14 and S100A16 may impair the infiltration and cytolytic activity of CD8⁺ T cells through focal adhesion‐Ras‐stimulating signalling pathway in PC. Overall, this study explores the multiple prognostic values and oncologic functions of the S100A family in PC.

Background and Objectives: Circular RNAs play a vital role in developing triple-negative breast cancer (TNBC). Likewise, the function of circRNAs in TNBC resistance to chemotherapy remains largely unknown. Here, we aimed to investigate whether circPLK1 has a biological efect on anthracycline resistance in TNBC. Methods: We identified circPLK1—a circRNA—using a circRNA microarray in TNBC cells and paired TNBC samples. We assessed the role of circPLK1 in anthracycline resistance in TNBC. Cytotoxicity assay, colony formation assay, and flow cytometry were performed as functional experiments. Western blot analysis, qRT-PCR, in situ hybridization, and immunohistochemistry were used to evaluate the expression of circPLK1, miR-940, and ETS1. RNA immunoprecipitation and luciferase reporter assay were conducted to evaluate the interaction among circPLK1, miR-940, and ETS1. We evaluated the prognosis value of circPLK1 and ETS1 in 240 TNBC patients. Results: The upregulation of circPLK1 in non-pCR TNBC patients receiving anthracyclines-based neoadjuvant chemotherapy was significantly associated with aggressive characteristics. Colony formation and doxorubicin resistance of TNBC cells were promoted by circPLK1 overexpression but inhibited by circPLK1 knockdown in vitro. circPLK1 overexpression facilitated doxorubicin resistance of TNBC in the nude mouse xenograft model. We found that circPLK1 could promote ETS1 expression by sponging miR-940. High circPLK1 and ETS1 expression were significantly associated with reduced survival in TNBC. Conclusion: circPLK1 plays a vital role in the resistance of TNBC to anthracycline and is associated with poor prognosis. The inhibition of circPLK1 may be a practical therapeutic approach to modulate anthracycline resistance in TNBC.

A comprehensive analysis of the immune response triggered by intraoperative radiation therapy (IORT) remains incomplete. In this study, single‐cell RNA sequencing and single‐cell T cell receptor sequencing are conducted on peripheral blood mononuclear cells (PBMCs) from patient with early‐stage breast cancer before and after IORT. Following IORT combined with surgery (defined as IORT+Surgery), PBMC counts remained stable, with increased proportions of T cells, mononuclear phagocytes, and plasma cells, and a reduction in neutrophil proportions. The cytotoxic score of CD8Teff_GZMK cells increased significantly post‐IORT. Communication between CD8Teff_GZMK cells and other immune cells via MIF_CD74 and MIF_TNFRSF14 is decreased after IORT. cDCs showed an upregulation of the MCH II signaling pathway, while memory B cells exhibited enhanced activation of the B cell pathway. T cell clones expanded significantly after treatment. IORT+Surgery demonstrated the ability to partially suppress the anti‐tumor effects of neutrophils. Flow cytometry analysis and co‐culture experiments are utilized to delve deeper into the functional alterations in T cells. IORT+Surgery significantly enhanced T cell cytotoxic activity. Blockade of PD‐1 of post‐IORT PBMCs shows higher T‐cell activity than that of pre‐IORT PBMCs. This research highlights IORT's impact on immune cells, offering insights for targeting immune responses in breast cancer.

Breast cancer (BC) prognosis and therapeutic sensitivity could not be predicted efficiently. Previous evidence have shown the vital roles of CDKN1C in BC. Therefore, we aimed to construct a CDKN1C‐based model to accurately predicting overall survival (OS) and treatment responses in BC patients. In this study, 995 BC patients from The Cancer Genome Atlas database were selected. Kaplan‐Meier curve, Gene set enrichment and immune infiltrates analyses were executed. We developed a novel CDKN1C‐based nomogram to predict the OS, verified by the time‐dependent receiver operating characteristic curve, calibration curve and decision curve. Therapeutic response prediction was followed based on the low‐ and high‐nomogram score groups. Our results indicated that low‐CDKN1C expression was associated with shorter OS and lower proportion of naïve B cells, CD8 T cells, activated NK cells. The predictive accuracy of the nomogram for 5‐year OS was superior to the tumour‐node‐metastasis stage (area under the curve: 0.746 vs. 0.634, p < 0.001). The nomogram exhibited excellent predictive performance, calibration ability and clinical utility. Moreover, low‐risk patients were identified with stronger sensitivity to therapeutic agents. This tool can improve BC prognosis and therapeutic responses prediction, thus guiding individualized treatment decisions.

Background: Estrogen receptor-positive and progesterone receptor-negative (ER + /PR-) breast cancer comprise a special type. More than 10% breast cancer patients belonged to ER + /PR-. Methods: In order to better understand this patient population, we utilized a unique dataset from China, examining the clinicopathological features and genomic profiles of ER + /PR- breast cancers. Our study involved three cohorts: Cohort 1 included 2120 unselected ER-positive female patients with re-evaluated clinicopathological and survival data; Cohort 2 comprised 442 ER-positive females who underwent genetic testing; and Cohort 3 consisted of 77 ER-positive/HER2-negative females tested with MammaPrint and BluePrint. Results: Patients were stratified into four categories based on the PR/ER ratio. Clinically, ER + /PR- tumors (PR/ER ratio = 0) showed the lowest proportion of T1 tumors (10.88%) and highest proportion of HER2-positive tumors (28.36%) than did other ER + /PR + tumors groups. The ER + /PR- group contained a higher number of underweight patients (20.20%). Independently of HER2 status, ER + /PR- patients demonstrated the poorest prognosis. Genomically, the most prevalent mutations were PIK3CA (50%) in ER + /PR + tumors and TP53 (65%) in ER + /PR- tumors. ER + /PR- tumors presented more frequent mutations in TP53, ERBB2, CDK12, SPEN, and NEB, with mutation rates of 65%, 42%, 27%, 13%, and 10%, respectively. Additionally, the Tumor Mutational Burden (TMB) was higher in the ER + /PR- group compared to the ER + /PR + group. The MammaPrint score for the ER + /PR-/HER2- group was significantly lower than that of other groups. In the BluePrint analysis, only four patients were classified as Basal-Type, all of whom were ER + /PR-/HER2-. Conclusions: In this study, we identified the clinical and genetic characteristics of ER + /PR- breast cancer patients in China. Distinct PR statuses indicated different biological processes of ER + breast cancer and survival outcomes. Future treatment strategies may need to be tailored for ER + /PR- patients.