Shuai Lin

Background: The reverse-sequence endoscopic nipple-sparing mastectomy with immediate prepectoral implant reconstruction (RSEM-IPI) has been described as a safe and feasible procedure for early-stage breast cancer. The aim of this study was to evaluate the learning curve for RSEM-IPI. Methods: Between January 2023 and February 2024, we collected data on 104 consecutive patients who underwent RSEM-IPI at our hospital (53 for group 1 and 51 for group 2). The surgeons in group 1 completed the endoscopic training and assistance, whereas the surgeons in group 2 did not. The learning curve was analyzed using the cumulative sum (CUSUM) method to assess changes in the operative times across the case sequence. Results: Among the 281 patients who received breast reconstruction surgeries, a total of 104 consecutive data were recorded and eligible. Both groups had higher rates of postoperative complications including bleeding, nipple-areolar complex (NAC) ischemia, skin ischemia, infection and longer drainage duration during the phrase 1 compared to the phrase 2. Notably, in terms of the most severe postoperative complications, implant expose and loss, both groups exhibited higher rates during the phrase 1. Breast-Q scores for group 1 in phases 1 and 2 were 66 and 84, respectively, while for group 2, they were 67 and 80. As compared with surgeons in group 2, well-trained surgeons in group 1 were more accessible for stable learning curve with fewer training patients (18 patients) and relatively lower rate of postoperative complications (p > 0.05). Conclusion: The estimated learning curve for RSEM-IPI was achieved after 18 cases in the well-trained surgeon group. The endoscopic training and assistance were critical to master the breast endoscopic surgeries for breast surgeons.

Background: The abundance of PD-L1 on the surface of tumor cells is a critical factor in sensitizing these cells to T cell-mediated immune killing. While abnormal glycosylation of PD-L1 is known to influence its expression and function, the precise regulatory mechanisms remain unclear. Methods: This study utilized bioinformatics analysis to explore the role of MGAT3, a key gene involved in the formation of the bisecting GlcNAc structure, in breast cancer (BC). Experimental approaches were employed to increase bisecting GlcNAc levels in BC cells, followed by assessments of PD-L1 expression, CD8⁺ T cell-mediated cytotoxicity, extracellular vesicle (EV)-associated PD-L1, and PD-L1/PD-1 interaction. Additionally, forskolin, a bisecting GlcNAc agonist, was combined with anti-PD-L1 antibody to evaluate its antitumor effects in vivo. Results: MGAT3 was found to be expressed at low levels in BC tissues but positively correlated with CD8⁺ T cell infiltration. Elevating bisecting GlcNAc levels in BC cells significantly enhanced the cytotoxic efficacy of CD8⁺ T cells. High bisecting GlcNAc modification promoted PD-L1 degradation via the lysosomal pathway, reducing PD-L1 expression and its binding to PD-1. Furthermore, increased bisecting GlcNAc levels reduced PD-L1 in tumor cell-derived EVs, impairing the EVs’ ability to block CD8⁺ T cells and indirectly enhancing T cell cytotoxicity. The combined use of forskolin and anti-PD-L1 antibody significantly increased CD8⁺ T cell abundance and activity, achieving a more effective antitumor response in vivo. Conclusions: These findings demonstrate that enhancing bisecting GlcNAc modification in BC cells promotes PD-L1 degradation and inhibits its binding to PD-1, thereby boosting CD8⁺ T cell-mediated cytotoxicity, providing a promising strategy for immune modulation in BC therapy.

Kidney Renal Clear Cell Carcinoma (KIRC) is a prevalent urinary malignancies worldwide. Glycosylation is a key post-translational modification that is essential in cancer progression. However, its relationship with prognosis, tumour microenvironment (TME), and treatment response in KIRC remains unclear. Expression profiles and clinical data were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus databases. Consensus clustering, Cox regression, and LASSO regression analyses were conducted to develop an optimal glycogene-related signature. The prognostic relevance of this molecular signature was rigorously analyzed, along with its connections to tumour microenvironment (TME), tumour mutation burden, immune checkpoint activity, cancer-immunity cycle regulation, immunomodulatory gene expression patterns, and therapeutic response profiles. Validation was performed using real-world clinical specimens, quantitative PCR (qPCR), and immunohistochemistry (IHC), supported by cohort analyses from the Human Protein Atlas (HPA) database. A glycogene-associated prognostic scoring system was established to categorize patients into risk-stratified subgroups. Patients in the high-risk cohort exhibited significantly poorer survival outcomes (p < 0.001). By incorporating clinicopathological variables into this framework, we established a predictive nomogram demonstrating strong calibration and a concordance index (C-index) of 0.78. The high-risk subgroup displayed elevated immune infiltration scores (p < 0.001), upregulated expression of immune checkpoint-related genes (p < 0.05), and an increased frequency of somatic mutations (p = 0.043). The risk score positively correlated with cancer-immunity cycle activation and immunotherapy-related signals. The high-risk groups also showed associations with T cell exhaustion, immune-activating genes, chemokines, and receptors. Drug sensitivity analysis revealed that low-risk patients were more sensitive to sorafenib, pazopanib, and erlotinib, whereas high-risk individuals responded better to temsirolimus (p < 0.01). qPCR and IHC analyses consistently revealed distinct expression patterns of MX2 and other key genes across the risk groups, further corroborated by the HPA findings. This glycogene-based signature provides a robust tool for predicting prognosis, TME characteristics, and therapeutic responses in KIRC, offering potential clinical utility in patient management.

Purpose: To assess the efficacy of neoadjuvant endocrine therapy in female HR‐positive/HER2‐negative breast cancer patients.Data and Methods: We identified female patients aged ≥18 years with cT1‐4N0‐XM0, HR(+), and HER2(−) breast cancer from the National Cancer Database. The patients who underwent surgery first were categorized as “surgery‐first,” while those who received NET before surgery were classified as “NET.” Propensity score‐matching, Cox proportional‐hazard model, variance inflation factors, and interaction analysis were employed to estimate the correlation between NET and survival outcomes.Results: Among 432,387 cases, 2914 NET patients and 2914 surgery‐first patients were matched. Compared with the surgery‐first group, the NET group received less adjuvant chemotherapy (p < 0.001). Furthermore, the NET group exhibited higher survival probabilities compared with the surgery‐first group (3 years: 91.4% vs. 82.1%; 5 years: 82.1% vs. 66.8%). Multivariate Cox analysis indicated that NET was associated with improved OS (surgery‐first vs. NET: HR 2.17, 95% CI: 1.93–2.44). Age over 55 years old, having public insurance, higher CDCC score, higher NSBR grade, ER(+)PR(−), and advanced clinical stage were related to worse OS (all p < 0.05). There was an interaction between age, race, income, and home and treatment regimen (all p < 0.05).Conclusion: NET may be a more effective treatment procedure than surgery‐first in female HR‐positive/HER2‐negative, non‐metastatic breast cancer patients. Future clinical studies with more detailed data will provide higher‐level evidence‐based data.

Introduction: For HR-positive/HER2-negative patients who can undergo breast-conserving surgery (BCS) but have a tumor size of 2–5 cm or 1–3 lymph node metastases, neoadjuvant chemotherapy (NAC) is still controversial. Methods: Patients with T2N0-1M0 HR-positive/HER2-negative BC who underwent BCS between 2010 and 2017 were selected from the SEER database. Propensity score matching (PSM) was used to minimize the influence of confounding factors. The overall survival (OS) and breast cancer-specific survival (BCSS) of patients were estimated by Kaplan‒Meier curves and Cox proportional hazard models. Independent prognostic factors were included to construct a nomogram prediction model. Results: A total of 6475 BC patients were enrolled, of whom 553 received NAC and 5922 received adjuvant chemotherapy (AC). In the T2N0-1M0 population and T2N1M0 subgroup, AC patients before PSM had better OS and BCSS than NAC patients. After PSM, there was no significant difference in OS or BCSS between the two groups. However, in the T2N0M0 subgroup, there was no difference in survival between the AC and NAC groups before and after PSM. Stratified analysis revealed that for complete response (CR) patients, survival was roughly equivalent between the NAC and AC groups. However, the survival of no response (NR) and partial response (PR) patients was significantly worse than that of AC patients. Cox analysis revealed that radiotherapy after BCS was an independent protective factor for OS. NAC is an independent risk factor for NR and PR patients. The nomogram has good prediction efficiency. Conclusion: NAC before BCS is not necessary for T2N0-1M0 HR-positive/HER2-negative BC patients.

Introduction: Immediate postmastectomy reconstruction for breast cancer has been widely used due to its unique esthetic and psychological effects. However, no other population‐based study has investigated the effects of different reconstruction types on the survival in patients with triple negative breast cancer (TNBC).Methods: We selected patients who met the eligibility criteria from the Surveillance, Epidemiology, and End Results cancer registry (N = 9760). We then assessed the effect of different reconstructive surgical approaches (implant, autologous, implant and autologous combined reconstruction) on the overall survival (OS) and breast cancer‐specific survival (BCSS) by using the Kaplan–Meier survival curve and Cox proportional hazard regression analyses. The nomograms were used to predict OS and BCSS. And the competitive risk model was used to assess breast cancer‐specific death (BCSD) and non‐breast cancer‐specific death (NBCSD).Results: Statistical analysis suggested that the three reconstruction methods had better OS and BCSS with lower hazard than mastectomy alone (log‐rank test, p < 0.05). Multivariate stratified analysis showed that patients aged 40–60 years had the greatest improvement in OS (Adjusted hazard ratio [AHR], 0.646; 95% Confidence Interval [CI], 0.439–0.950; p = 0.026) with combined reconstruction. BCSS could be improved only by implant reconstruction (AHR, 0.672; 95% CI, 0.514–0.878; p = 0.004). In addition, autologous reconstruction (AHR, 0.570; 95% CI, 0.350–0.929; p = 0.024) and implant reconstruction (AHR, 0.538; 95% CI, 0.339–0.853; p = 0.008) improved OS in patients >60 years of age. The survival prediction model quantified the survival benefits of TNBC patients undergoing different surgeries. Moreover, the C‐indexes showed the good predictive ability of the nomograms.Conclusions: Our results suggest that for TNBC patients, there is a survival benefit of immediate postmastectomy reconstruction compared with mastectomy alone. Among them, implant reconstruction has the most obvious advantage.

Background: Breast cancer (BC) is the most common malignant tumor worldwide. Apoptosis and hypoxia are involved in the progression of BC, but reliable biomarkers for these have not been developed. We hope to explore a gene signature that combined apoptosis and hypoxia‐related genes (AHGs) to predict BC prognosis and immune infiltration.Methods: We collected the mRNA expression profiles and clinical data information of BC patients from The Cancer Genome Atlas database. The gene signature based on AHGs was constructed using the univariate Cox regression, least absolute shrinkage and selection operator, and multivariate Cox regression analysis. The associations between risk scores, immune infiltration, and immune checkpoint gene expression were studied using single‐sample gene set enrichment analysis. Besides, gene signature and independent clinicopathological characteristics were combined to establish a nomogram. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on the potential functions of AHGs.Results: We identified a 16‐AHG signature (AGPAT1, BTBD6, EIF4EBP1, ERRFI1, FAM114A1, GRIP1, IRF2, JAK1, MAP2K6, MCTS1, NFKBIA, NFKBIZ, NUP43, PGK1, RCL1, and SGCE) that could independently predict BC prognosis. The median score of the risk model divided the patients into two subgroups. By contrast, patients in the high‐risk group had poorer prognosis, less abundance of immune cell infiltration, and expression of immune checkpoint genes. The gene signature and nomogram had good predictive effects on the overall survival of BC patients. GO and KEGG analyses revealed that the differential expression of AHGs may be closely related to tumor immunity.Conclusion: We established and verified a 16‐AHG BC signature which may help predict prognosis, assess potential immunotherapy benefits, and provide inspiration for future research on the functions and mechanisms of AHGs in BC.

Hepatocellular carcinoma (HCC) seriously endangers humans. In traditional Chinese medicine, Marsdenia tenacissima (MTE) has anti-inflammatory, antiasthmatic, antihypertensive, and anticancer effects. This study reveals the antiproliferative effect of MTE on the HCC cells in vitro and provides a theoretical basis for the development and clinical application of anti-HCC agents. Methods. MHCC-97H and HepG2 cells were cultured in vitro and exposed to various concentrations and durations of MTE, and an MTT assay was used to detect the effects of MTE on cell proliferation. Transmission electron microscopy revealed the morphological changes in the two cell lines after MTE stimulation. The MTE effects on the apoptosis and cell cycle distribution of the cell lines were detected by flow cytometry. Western blotting and qRT-PCR were used to detect target gene expression at the protein and mRNA levels, respectively. Results. MTE reduced the viability of the MHCC-97H and HepG2 cells in a dose- and time-dependent manners ( ). Autophagic vesicles and apoptotic bodies were found in the MHCC-97H and HepG2 cells after MTE incubation, and the Annexin V-PI assay showed that the apoptotic rates of the cell lines increased with increasing MTE concentration ( ). Autophagy inducer rapamycin promoted the MTE-induced apoptotic rates of the cell lines, whereas autophagy inhibitor chloroquine inhibited the apoptotic rates. More cells in the S phase were found in the two cell lines after MTE treatment ( ). After MTE incubation, MIF, CD47, and beclin-1 protein levels significantly increased. Furthermore, in the MTE group, Akt, mTOR, and caspase3 expressions decreased; however, LC 3 expression increased, which was significantly different from the control group ( ). Conclusions. MTE inhibited proliferation and induced autophagy, apoptosis, and S phase cell cycle arrest in the MHCC-97H and HepG2 cells. These effects might be related to the activation of MIF and mTOR signaling inhibition.

Purpose: We aimed to characterize the expression patterns of glycolysis and hypoxia genes in colon cancers as well as their value in prognosis and immune microenvironment. Methods: The expression profiles were acquired from the Cancer Genome Atlas database. Enrichment of hypoxia and glycolysis gene sets in colon cancer was identified by gene set enrichment analysis. Then, a prognostic signature was built up after Cox regression analyses, and overall survival analysis validated the predictive ability. Immune status and infiltration in cancer tissues were explored using the single sample gene set enrichment analysis and CIBERSORT algorithm. A nomogram model integrating clinical variables and the gene signature was established and assessed. Results: Altogether, 378 cancer and 39 control cases were enrolled. Three glycolysis gene sets and two hypoxia gene sets were enriched in colon cancer (P < 0.05). Five independent genes (ENO3, GPC1, P4HA1, SPAG4, and STC2) were significantly correlated with prognosis of colon cancer patients. Patients with higher risks had significantly better prognosis than those with lower risks (P = 0.002 and AUC = 0.750), which was also observed in the elderly, female and stage I–II subgroups (P < 0.05). In high-risk cases, proportion of NK cells resting increased (P < 0.05) while that of dendritic cells activated (P < 0.05), dendritic cells resting (P < 0.01) and monocytes (P < 0.01) decreased. Besides, expressions of 22 checkpoint genes were found abnormal in groups with different risks (P < 0.05). The predictive nomogram presented satisfactory performance with C-index of 0.771 (0.712– 0.830). The area under ROC curve was 0.796 and 0.803 for 3- and 5-year survival prediction, respectively. Conclusion: A glycolysis and hypoxia combined gene signature was a promising method to evaluate the prognosis and immune infiltration of colon cancer patients, which may provide a new tool for cancer management.