Cancer remains a major cause of global mortality, necessitating the identification of novel biomarkers to improve prognosis and guide therapy. ABCA1, an ATP-binding cassette transporter involved in cholesterol efflux, has been implicated in tumorigenesis, yet its pan-cancer roles and clinical relevance are not fully understood. We conducted a comprehensive multi-omics analysis of ABCA1 across diverse cancers, evaluating its expression, prognostic significance, genomic alterations, tumor immune microenvironment interactions, and regulatory mechanisms. ABCA1 expression was dysregulated in multiple malignancies and associated with poor prognosis in STAD, STES, and LGG, though favorable outcomes were observed in KIRC. It correlated with genomic instability markers (TMB, MSI, HRD), immune cell infiltration, and cancer stemness. Pathway analyses revealed enrichment in cholesterol metabolism and efferocytosis-related pathways. Among the cancer types examined, esophageal squamous cell carcinoma (ESCC) was selected for exploratory functional validation due to its prognostic relevance. In vitro, ABCA1 knockdown inhibited proliferation, invasion, and migration in ESCC cell lines. In silico drug sensitivity analysis suggested potential associations with dasatinib response and panobinostat resistance, warranting further experimental validation. Collectively, these findings highlight the context-dependent associations of ABCA1 with cancer progression, immune modulation, and genomic integrity, suggesting its potential utility as a prognostic biomarker that warrants further investigation for therapeutic targeting.

INTRODUCTION:Esophageal cancer (EC) remains a global health challenge with high incidence and mortality. While sEV-related genes (ERGs) are emerging as key players in the tumor microenvironment, their diagnostic and pathogenic roles in EC are still poorly characterized. METHODS:This study employed integrated bioinformatics approaches to identify ERGbased diagnostic biomarkers and molecular mechanisms in EC. Four GEO datasets were analyzed to identify differentially expressed genes (DEGs), which were cross-referenced with ERGs from GeneCards and the literature. Functional enrichment analyses (GO/KEGG), Cytoscape network analysis, and machine learning algorithms (LASSO, SVM, random forest) were used to prioritize diagnostic markers. Immune infiltration patterns were assessed via ssGSEA, and key genes were validated by qRT‒PCR in EC and normal cells. RESULTS:We identified 456 DEGs, including 34 sEV-related ERDEGs enriched in bacterial defense response, secretory granule lumen, calcium-dependent protein binding, and pathways such as proteoglycans in cancer and IL-17 signaling. GSEA highlighted cell cycle, ECM-receptor interaction, and DNA replication as central mechanisms. DISCUSSION:Machine learning pinpointed EpCAM and RUVBL1 as robust diagnostic biomarkers, validated by their elevated expression in EC cell lines. Immune infiltration analysis revealed correlations between these genes and 20 immune cell types, underscoring their relevance to the tumor microenvironment. CONCLUSION:EpCAM and RUVBL1 are promising diagnostic biomarkers for EC, linking sEV-mediated pathways to disease progression. These findings provide insights into EC pathogenesis and highlight potential therapeutic targets.

Neoadjuvant immunochemotherapy (nICT) has emerged as a promising perioperative strategy for locally advanced gastric and gastroesophageal junction cancer (LAGC/EGJC), yet its survival benefit beyond pathological response and optimal patient selection remain uncertain. We conducted a systematic review and meta-analysis to evaluate the efficacy, safety, and biomarker stratification of nICT compared with neoadjuvant chemotherapy (nCT). PubMed, Embase, Web of Science, and the Cochrane Library were searched through August 30, 2025. Comparative studies of nICT versus nCT and single-arm nICT cohorts were included. Overall survival (OS) and recurrence-free survival (RFS) were primary outcomes. Fifteen comparative studies and thirty-four single-arm or biomarker datasets were included. Compared with nCT, nICT significantly improved OS (HR = 0.80, 95 % CI 0.70-0.92) and RFS (HR = 0.78, 95 % CI 0.69-0.87), and achieved higher pathological complete response, major pathological response, and R0 resection rates. Although treatment-related adverse events were more frequent with nICT, postoperative recovery and complication rates were comparable. Single-arm analyses showed pooled pathological complete and major pathological response rates of approximately 20 % and 43 %, with encouraging 2-year OS and RFS. Biomarker analyses demonstrated enrichment of pathological response in patients with PD-L1 CPS ≥ 1/≥ 5 and dMMR/MSI-H, whereas tumor mutational burden and Epstein-Barr virus status showed inconsistent discriminatory value. Meta-regression revealed no significant effect modification. Overall, nICT provides pathological and early survival improvement without compromising perioperative safety, supporting its integration into perioperative strategies for LAGC/EGJC.

Single-cell transcriptomics reconstructs developmental trajectories, but quantitative frameworks for population-level transcriptional reorganization during lineage commitment remain underdeveloped, limiting systems-level insights into cell fate specification. Here we introduce a spectral framework based on singular value decomposition of the cell-by-gene expression matrix, applied to murine pancreatic endocrine development (GSE132188). We derive two collective observables: R eff , the effective number of active modes quantifying the dimensionality of collective transcriptional states, and R 3 , a third-order statistic measuring mode-weight distribution asymmetry. Along pseudotime, endocrine differentiation exhibits a transient R eff minimum at the Ngn3 -high state, marking a low-dimensional population-wide commitment bottleneck. R 3 rises during Fev + and terminal differentiation, reflecting asymmetric stabilization of lineage-specific regulatory programs during fate diversification. A random-order null model reduces these signatures, confirming they reflect coherent developmental progression rather than sampling effects. The leading eigenmodes recover biologically interpretable transcriptional programs underlying progenitor-to-mature endocrine progression and transient endocrine commitment. Together, these results support cell-fate specification as an ordered, collective reorganization in high-dimensional expression-state space, and demonstrate that physics-inspired spectral observables complement standard single-cell trajectory analysis to uncover system-level developmental principles.

The development of second primary cancers (SPCs) has become an important late effect in gastric cancer (GC) survivors, yet its incidence, risk factors, and clinical implications remain poorly defined. This study aimed to evaluate the long-term risk of SPCs, identify clinical factors associated with SPC occurrence, and describe detection patterns and stage distribution of SPCs during long-term follow-up. Patients with GC who underwent curative-intent radical gastrectomy between 2007 and 2021 were identified from the Multidisciplinary Alliance of Gastric Integrative Studies (MAGIS) cohort. Clinical factors associated with SPC occurrence were selected using LASSO-penalized Cox regression, and exploratory risk-based stratification was performed. Stage distribution was descriptively compared between SPCs detected during asymptomatic surveillance and those diagnosed after symptom onset. Among 11,027 GC survivors (8,519 men and 2,508 women), 241 (2.19

Background:Immune checkpoint inhibitors (ICIs) in combination with chemotherapy have become the standard treatment for advanced adenocarcinoma of the esophagogastric junction (AEG). While perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) remains the global standard for locally advanced resectable AEG, its substantial hematologic toxicity and perioperative tolerability concerns may limit broader adoption in some Asian patients in real-world clinical practice. This study aimed to assess the perioperative feasibility and safety of neoadjuvant adebrelimab combined with chemotherapy (nab-paclitaxel, lobaplatin, and S-1) in patients with resectable, locally advanced AEG. Methods:Between November 2023 and April 2025, 24 patients with clinically staged cT3-4aNanyM0 or cT1-2N+M0 resectable AEG were prospectively enrolled at a single center. Patients received two 3-week cycles of neoadjuvant adebrelimab plus nab-paclitaxel, lobaplatin, and S-1, followed by surgery scheduled 4-6 weeks after treatment completion. Survival follow-up was censored on 19 October 2025. The primary endpoint was pathological complete response (pCR) rate. Results:Among the 24 enrolled patients, the median age was 62 years, 83.3% were male, 37.5% had Siewert type III tumors and programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥1. Twenty patients (83.3%) subsequently underwent surgery, all achieving R0 resection. In the intention-to-treat (ITT) population, the pCR and major pathological response (MPR) rates were 16.7% [95% confidence interval (CI): 4.7-37.4%] and 29.2% (95% CI: 12.6-51.1%), respectively. Corresponding rates in the surgery population were 20.0% (95% CI: 5.7-43.7%) and 35.0% (95% CI: 15.4-59.2%). The objective response rate (ORR) was 79.2%, and the disease control rate (DCR) was 100%. At a median follow-up of 9.1 months, the estimated 1-year event-free survival (EFS) and overall survival (OS) rates were 80.8% and 88.9%, respectively. Treatment-related adverse events (TRAEs) were predominantly grade 1-2, with only 1 patient (4.2%) experiencing a grade 3 TRAE. No grade 4-5 TRAEs or treatment-related deaths occurred. There was 1 patient (5.0%) who experienced a grade 3 surgical complication. Conclusions:Neoadjuvant adebrelimab combined with triplet chemotherapy demonstrated acceptable perioperative feasibility, manageable toxicity, and preliminary pathological antitumor activity in patients with locally advanced AEG. Given the exploratory single-arm design and short follow-up, the findings should be considered hypothesis-generating and require validation in larger multicenter randomized trials.

Neoadjuvant chemotherapy improves downstaging and survival in locally advanced gastric or esophagogastric junction adenocarcinoma (LAGC/EGJC), but the incremental benefit of adding programmed death-1 (PD-1) blockade and pragmatic perioperative biomarkers remain uncertain. We conducted a retrospective cohort of patients with clinically staged cT2N + M0 or cT3–4bNanyM0 (IIa–IVa) LAGC/EGJC who received neoadjuvant PD-1 inhibitor plus chemotherapy or chemotherapy alone, followed by D2 gastrectomy. After one-to-one propensity score matching, pathological response, radiologic response, recurrence-free survival (RFS), overall survival (OS), and safety were compared between the two groups. Exploratory analyses assessed PD-L1 combined positive score (CPS), mismatch repair (MMR) status, blood-based indices (NLR, PLR, SII, PNI). From January 2018 to December 2024, 360 patients were analyzed (n = 180 per group) after matching. The rates of ORR (70.56

Background: The obesity paradox has attracted growing attention in oncology, yet the specific CT-derived body composition compartments that drive survival differences in colorectal cancer (CRC) remain ill-defined. This study aimed to identify the key muscle and adipose tissue metrics underlying this prognostic heterogeneity and to construct an optimal, population-specific prediction model based on these parameters. Methods: In this multicenter retrospective cohort study, we included patients who underwent surgical resection with pathologically confirmed CRC from three regional hospitals in China and who had abdominal CT scans available for body composition analysis. The cohort was randomly divided into training and validation cohorts at a 7:3 ratio. Adipose and skeletal muscle areas were measured at six contiguous intervertebral disc levels from T12/L1 to L5/S1, and independent models were constructed for each level. The primary outcomes were overall survival (OS) and cancer-specific survival (CSS). OS was assessed using Cox proportional hazards models, while CSS was analyzed with competing risks regression. Findings: A total of 688 patients were enrolled and randomly allocated to a training cohort (n = 450) and a validation cohort (n = 238). Greater visceral-to-subcutaneous fat ratio (VSR) and lower skeletal muscle index (SMI) were associated with worse outcomes, while patients with an intermediate total fat index (TFI) had more favorable prognosis than those with either high or low TFI. The L2/L3 disc-level model yielded the optimal prediction of OS and CSS for colon cancer, whereas the L4/L5 level performed best for rectal cancer. Independent risk factors identified for colon cancer included age, TNM stage, carcinoembryonic antigen (CEA) level, TFI, and SMI; for rectal cancer, age, TNM stage, CEA level, histological grade, TFI, VSR, and SMI were independent predictors. The resulting prognostic nomogram demonstrated good calibration and discrimination in both the training and validation cohorts. Interpretation: CT-derived body composition metrics from routine scans independently predict OS and CSS in CRC, offering mechanistic insight into the obesity paradox. Site-specific models—L2/L3 for colon cancer and L4/L5 for rectal cancer—were identified as optimal, and the resulting prognostic nomogram enables early identification of high-risk patients to support personalized weight management and clinical decision-making.

e16131 Background: Despite standard neoadjuvant chemotherapy and radical resection, patients with locally advanced gastric cancer (GC) face a high risk of recurrence and poor long-term survival. Although intensified chemotherapy with nab-paclitaxel plus SOX has shown improved tumor regression, pathological responses remain limited. Whether adding immunotherapy can further enhance pathological benefit while preserving surgical feasibility remains unclear. This trial evaluated the efficacy and safety of serplulimab, a PD-1 inhibitor, combined with nab-paclitaxel and SOX as neoadjuvant therapy under close safety monitoring. Methods: This multicenter, randomized, double-blind controlled trial enrolled patients with pathologically confirmed locally advanced GC or gastroesophageal junction (GEJ) adenocarcinoma and an ECOG performance status of 0-1. Patients were assessed by a multidisciplinary team as having potential for R0 resection, but upfront surgery was deemed technically challenging. Patients were randomized to receive 3 cycles of neoadjuvant serplulimab plus nab-paclitaxel and SOX (immunochemotherapy) or placebo plus nab-paclitaxel and SOX (chemotherapy), followed by curative-intent gastrectomy with D2 lymphadenectomy. The primary endpoints were pathological complete response (pCR) and safety. Secondary endpoints included major pathological response (MPR), R0 resection rate. Results: A total of 98 patients were screened, and 51 eligible patients (median age, 62 years) were enrolled and randomized to the immunochemotherapy (n = 23) or chemotherapy (n = 28) group. All patients received surgery after neoadjuvant. The pCR rate was significantly higher in the immunochemotherapy group than in the chemotherapy group (30.4% vs 3.6%; P = 0.025), as was the numerically higher MPR rate (39.1% vs 17.9%; P = 0.090). The R0 resection rate was comparable between the two groups (100.0% vs. 92.9%), while a significantly higher rate of postoperative N downstaging was observed in the immunochemotherapy group (78.3% vs 46.4%; P = 0.021). The incidence of grade 3-4 adverse events (AEs) was 19.6% (n = 10), with a comparable safety profile between the two groups. No grade 5 toxicity was observed. Crucially, AEs were manageable and did not delay neoadjuvant treatment or postponement of surgery in either group. Conclusions: Neoadjuvant serplulimab combined with an intensified regimen of nab-paclitaxel and SOX showed promising efficacy in fit patients with locally advanced GC/GEJ adenocarcinoma. This strategy significantly improved pCR rates and promoted nodal downstaging, with a safety profile that did not compromise surgical feasibility. The study is ongoing; long-term follow-up and exploratory analyses are required to further evaluate the durability and full potential of this strategy. Clinical trial information: NCT06576921 .

Aims: We aimed to develop Ferroptosis-Related Gene (FRG) signatures to predict overall survival (OS) along with disease-free survival (DFS) in individuals with colorectal cancer (CRC). Background: Prediction of CRC prognosis is challenging. Ferroptosis constitutes a newly reported kind of cell death, and its association with CRC prognosis remains unexplored. Objective: This research endeavored to establish a prognostic risk signature for colorectal cancer by leveraging ferroptosis-related genes (FRGs), with the objective of refining prognostic precision in clinical settings. Methods: The clinical data and mRNA expression profiles were obtained from The Cancer Genome Atlas (TCGA) colorectal cancer cohorts. The Lasso algorithm was employed to develop the overall survival (OS) and disease-free survival (DFS) prediction models. These models were subsequently validated using independent data from GSE38832. Results: Our research unveiled a significant difference in the expression levels of 85% of ferroptosis-related genes (FRGs) between CRC tissues and paracancer tissues. Out of these, 11 prognostic genes were pinpointed through univariate Cox analysis. By employing two models, patients were stratified into low- and high-risk groups based on predicted risk scores, which were subsequently validated as independent prognostic factors via multivariate Cox analysis. The robustness of these models was further confirmed through Receiver Operating Characteristic (ROC) curve analysis. Functional enrichment analysis indicated a predominance of cancer-associated pathways in the high-risk group, including WNT signaling, along with variations in immune status between the two risk categories. Leveraging the Connectivity Map (CMap) database, a total of sixteen potential therapeutic drugs were identified. Additionally, in vitro experiments corroborated that Farnesyl-Diphosphate Farnesyltransferase 1 (FDFT1) was underexpressed in CRC and exhibited tumor suppressive properties. More specifically, FDFT1 may augment ferroptosis in CRC by modulating the expression of the Iron-Sulfur Cluster Assembly Enzyme (ISCU). Conclusion: Our study highlighted the significance of ferroptosis-related genes in the pathogenesis of CRC and underscored the potential of ferroptosis-related gene-based risk signatures as valuable tools for improving prognostic accuracy and tailoring therapeutic strategies. However, the validity of these predictive models required further validation through real- world studies to ensure their reliability and applicability.

Background:Neoadjuvant immunochemotherapy is increasingly used for resectable locally advanced gastric cancer (LAGC) and gastroesophageal junction (EGJ) adenocarcinoma, yet the optimal chemotherapy backbone for PD-1 blockade remains unclear. We compared neoadjuvant PD-1 inhibitor plus S-1+oxaliplatin (SOX) versus PD-1 inhibitor plus 5-FU+oxaliplatin+Docetaxel+Leucovorin (FLOT) in a real-world cohort. Methods:This single-center retrospective study included patients with resectable, HER2-negative LAGC/EGJ adenocarcinoma (cT3-4b, any N+, M0; ECOG 0-1) treated between July 2020 and July 2025. Patients received neoadjuvant PD-1 inhibitor plus SOX or PD-1 inhibitor plus FLOT (3-5 cycles) followed by D2 gastrectomy. The primary endpoint was pathological complete response (pCR). Secondary endpoints included major pathological response (MPR), radiologic response (RECIST v1.1), perioperative outcomes, treatment-related adverse events (CTCAE v5.0), recurrence-free survival (RFS), and overall survival (OS). Survival was analyzed using Kaplan-Meier methods and Cox proportional hazards models. Results:Overall, 247 patients were enrolled (PD-1+SOX, n=141; PD-1+FLOT, n=106) with comparable baseline characteristics. Radiologic outcomes were similar between groups (ORR: 70.92% vs 66.98%, p=0.507; DCR: 87.23% vs 85.85%, p=0.752). Pathological responses did not differ significantly (pCR: 20.57% vs 16.98%, p=0.477; MPR: 37.59% vs 31.13%, p=0.292). Any-grade treatment-related adverse events occurred in 67.38% and 75.47% of patients, and grade ≥3 events in 19.15% and 26.42%, respectively; no treatment-related deaths occurred. R0 resection rates were high (100% vs 99.06%). Operative time and estimated blood loss were higher in the PD-1+FLOT group (p=0.010 and p=0.040), while postoperative complication rates were comparable. With median follow-up of 21 months (12-52) and 20 months (10-46), there were no significant differences in OS (HR 1.155, 95% CI 0.624-2.138) or RFS (HR 0.805, 95% CI 0.461-1.405). In multivariable analyses, non-MPR was an independent risk factor for both OS and RFS. Conclusions:Neoadjuvant PD-1 inhibitor plus SOX and plus FLOT yielded comparable response rates, survival outcomes, and safety profiles in patients with resectable LAGC/EGJ adenocarcinoma. PD-1+SOX was associated with less operative burden, and MPR remained independently associated with OS and RFS, supporting its value for risk stratification and treatment optimization.

Proliferation and metastasis are the core malignant characteristics in esophageal squamous cell carcinoma (ESCC) that contribute to poor prognosis. However, the mechanisms underlying cell proliferation and metastasis remain elusive. We explored the function of high-mobility group box (HMGB3) in promoting ESCC progression. HMGB3 expression in ESCC tissues and cell lines was quantified using quantitative PCR, Western blotting, and immunohistochemistry. The proliferative and migratory characteristics of ESCC cells were assessed using in vitro and in vivo assays, respectively. An RNA sequencing analysis was conducted to identify the downstream signaling pathways of HMGB3. Co-immunoprecipitation was performed to identify HMGB3-interacting proteins. HMGB3 transcriptional regulation was investigated using luciferase reporter and chromatin immunoprecipitation assays. Elevated levels of HMGB3 were observed in both patient-derived ESCC tissues and ESCC cell lines and were correlated with poor patient prognosis. HMGB3 up-regulation promoted ESCC proliferation and metastasis, whereas HMGB3 down-regulation inhibited these processes. Mechanistically, homeodomain protein transforming growth factor beta (TGF-u03B2)-induced factor homeobox 2 (TGIF2) transcriptionally up-regulates HMGB3. HMGB3 subsequently activates TGF-u03B2 signaling through its regulation of and interaction with toll-like receptor 3 (TLR3), ultimately promoting ESCC proliferation and metastasis. Clinically, HMGB3 expression was positively correlated with TGIF2 and TGF-u03B2, and patients with ESCC who positively co-expressed TGIF2/HMGB3, HMGB3/TGF-u03B2, or TGIF2/TGF-u03B2 exhibited poor prognosis. The functional role of HMGB3 in ESCC proliferation and metastasis was illustrated in our research. Targeting the TGIF2/HMGB3/TLR3/TGF-u03B2 axis has the potential to serve as a promising therapeutic approach.

Gastric cancer remains a formidable global health challenge, with drug resistance being a primary contributor to its high mortality rates. Therefore, understanding the mechanisms driving drug resistance is crucial for developing more effective therapeutic interventions. Utilizing high content screening technology, we identified let-7e-5p and miR-125a-5p as the key regulators of drug resistance in GC, both being members of the miR-99b cluster. Findings from GC cells, organoids and PDX models demonstrated that overexpression of the miR-99b cluster sensitized GC to cisplatin, likely through its inhibitory effects on mitochondrial respiratory function, particularly OXPHOS. We further demonstrated that multiple components, especially SDHC subunit of respiratory complex II, were regulated by miR-99b cluster and played critical roles in GC chemoresistance. Then, through a comprehensive screen of epigenetic compounds, we identified KMT5A as a key upstream repressor of the miR-99b cluster in GC, which reinforces the H4K20me1 modification within the miR-99b cluster region. Moreover, elevated KMT5A expression and decreased miR-125a-5p expression indicated both poorer prognosis and chemo-resistance in patients with GC. This study highlights the multifaceted roles of the miR-99b cluster in GC and offers novel perspectives for the development of innovative therapeutics aimed at overcoming chemoresistance and enhancing treatment efficacy for GC patients.

411 Background: Recently, several clinical trials have demonstrated synergistic efficacy by combining immune checkpoint inhibitors (ICIs) with chemotherapy. However, only a subset of patients (pts) derived benefits. Combining ICIs with agents blocking immunosuppressive pathway may expand the clinical benefit of ICIs to more pts. Transforming growth factor β (TGF-β) participates in tumor immune escape. SHR-1701, a novel bifunctional fusion protein consisting of a monoclonal antibody targeting PD-L1 fused with the extracellular domain of TGF-β receptor II, was evaluated in a phase II trial (ChiCTR2000039909) to assess its efficacy and safety when combined with chemotherapy for pts with unresectable locally advanced, recurrent or metastatic ESCC in China. Methods: This trial enrolled treatment-naive pts with histologically or cytologically confirmed unresectable locally advanced, recurrent, or metastatic ESCC. Eligible pts received SHR-1701 (30mg/kg, iv, d1, q3w) in combination with up to six cycles of albumin-bound paclitaxel (125mg/m 2 , iv, d1, d8, q3w) and cisplatin (75mg/m 2 , iv, d1, q3w). For those without progressive disease, maintenance treatment was administered with SHR-1701 monotherapy until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety. Results: At the data cut-off, March 1, 2024, 24 pts had received at least one dose of the study treatment and were included in both the intention-to-treat (ITT) analysis and safety analysis sets. 3 and 12 pts achieved confirmed complete and partial responses, respectively. The confirmed ORR was 62.5% and DCR was 87.5%. With a median follow-up of 20.8 months (95% CI, 15.5-NR), the median duration of response was 9.1 months (95% CI, 6.9-NR). The median PFS was 10.8 months (95% CI, 7.8-NR) and the median OS was 26.1 months (95% CI, 8.6-NR). 12-month PFS and OS rates were 41.4% (95% CI, 22.5-76) and 64.8% (95% CI, 47.8-87.9), respectively. Grade 3-4 treatment-related adverse events occurred in 11 (45.8%) pts and no treatment-related death was observed. Conclusions: The results highlighted that SHR-1701 plus chemotherapy as first-line therapy maintained long-term, durable survival benefit in pts with advanced ESCC. Clinical trial information: ChiCTR2000039909.

OBJECTIVE/BACKGROUND:The RNPLS-01 trial aimed to evaluate the efficacy and safety of ramucirumab (a VEGFR2 antagonist) combined with nab-paclitaxel, lobaplatin, and S-1 (RNPLS group) versus nab-paclitaxel, lobaplatin, and S-1 alone (NPLS group) in neoadjuvant therapy for advanced gastric cancer (GC), as part of the RNPLS-01 prospective randomized controlled trial. METHODS AND ANALYSIS:RNPLS-01 trial enrolled 140 patients with advanced GC across two cohorts (neoadjuvant therapy: n = 70; conversion therapy: n = 70). This report focuses on the neoadjuvant cohort where patients were randomized 1:1 to receive either RNPLS (n = 35) or NPLS (n = 35). Primary endpoint was pathological complete response (pCR). Secondary endpoints included R0 resection rate, objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). RESULTS:The RNPLS group demonstrated significant improvements in post-operative T stage ( P = 0.008), N stage ( P = 0.001), and AJCC (American Joint Committee on Cancer) clinical stage ( P = 0.003) compared to controls. The RNPLS group demonstrated significantly higher pCR rates compared to the NPLS group (22.9% vs. 2.9%, P <0.0001). The R0 resection rate was 85.7% in the RNPLS group versus 82.9% in the NPLS group. The RNPLS group achieved a significantly higher ORR compared to the NPLS group (68.6% vs. 25.7%, P = 0.001), while DCRs were comparable between the two groups (94.3% vs. 77.1%, P = 0.055). Treatment-related adverse events (TRAEs) were confined to Grade 1-2 severity, with no Grade 3-4 events reported in either group. The RNPLS group showed a TRAE incidence of 80.0%, versus 88.6% in the NPLS group ( P = 0.324). Neither group exhibited surgical complications during the study period. CONCLUSION:Ramucirumab combined with nab-paclitaxel, lobaplatin, and S-1 significantly enhances the pCR rate and ORR in neoadjuvant therapy of locally advanced GC patients, while maintaining an acceptable safety profile.

Purpose:Cell division cycle protein 45 (CDC45) plays a crucial role in DNA replication. This study investigates its role in breast cancer (BC) and its impact on tumor progression. Methods:We utilized the GEO database to screen differentially expressed genes (DEGs) and conducted enrichment analysis on these genes. We established a Nomogram model based on CDC45 and other clinical indicators. Additionally, we performed protein-protein interaction (PPI) network construction, drug sensitivity analysis, and immune correlation analysis of CDC45. The function of CDC45 was further verified through cell and animal experiments. Results:CDC45 is highly expressed in most tumors, including BC. The expression level of CDC45 was significantly associated with age, sex, race, cancer stage, and molecular subtypes (all p < 0.05). CDC45 was incorporated into a Nomogram model, which showed moderate accuracy in predicting patient prognosis. We also analyzed the co-expression genes of CDC45, including TOPBP1, GINS2, MCM5, GINS1, GINS4, POLE2, MCM2, MCM6, MCM4, and MCM7. Furthermore, CDC45 expression was closely linked to immune infiltration levels, immune checkpoint inhibitors, and the therapeutic response to small molecule drugs. Finally, both in vitro and in vivo experiments confirmed the cancer-promoting effect of CDC45 in BC. Conclusion:The expression level of CDC45 is linked to the prognosis, immune infiltration, and drug sensitivity of BC. In vitro and in vivo experiments have confirmed that CDC45 acts as a cancer-promoting protein in breast cancer.

ABSTRACT:Recent studies have revealed aberrant expression patterns of the autophagy-associated transmembrane protein etoposide-induced 2.4 (EI24) in diverse cancer types, prompting investigations into its potential as a biomarker for cancer. These findings underscore the multifaceted roles of EI24 in regulating critical processes such as tumor metastasis, proliferation, angiogenesis, drug resistance, tumor microenvironment, and autophagy, both indirectly and directly. Such insights also provide a foundation for further elucidating the underlying mechanisms of EI24's involvement in tumorigenesis, thereby facilitating the development of novel therapeutic approaches. In this review, we present the latest advancements in EI24 research within the realm of tumor biology. We delve into the intricate molecular mechanisms governing EI24's functions across various tumor types and its diagnostic and prognostic significance. In addition, we analyze emerging therapeutic strategies targeting EI24 in tumors, offering insights into its potential as a future therapeutic target. A comprehensive understanding of EI24's role in tumor biology is crucial for devising innovative therapeutic approaches tailored to the diverse complexities of various cancer types. By integrating mechanistic insight with translational potential, EI24 represents a key node linking biological understanding to next-generation diagnostic and therapeutic innovations.

As a major complication after esophageal cancer (EC) surgery, postoperative pulmonary infection (PPI) is speculated to be associated with quality of life and survival after surgery. This study is aimed to explore the influence of PPI on the reality and establish a nomogram to predict PPI. Data of patients undergoing esophagectomy was collected between January, 2016 and December, 2020 and divided into PPI and without PPI groups. Hospital costs and overall survival (OS) were compared between two groups. Univariate-multivariate analysis and LASSO-multivariate logistic regression were carried out to identify risk factors, and then two models were established based on them. To choose the better one, the receiver operating characteristic (ROC), the area under curve (AUC) and K-fold cross validation were compared between the models. The incidence of PPI in 633 esophageal cancer patients was 30.2

Hepatocellular carcinoma (HCC) is one of the commonly lethal malignancies worldwide and represents a major global health-care challenge. We have previously demonstrated that plumbagin (PLB) could inhibit the development of tumor in liver, but the mechanism is still not fully clear. Here we identified a transcription repressor-homeobox containing 1 (HMBOX1) as a regulator in the development of HCC.Knockdown of HMBOX1 resulted into expansive of tumor cells, while overexpression led to growth inhibition. Mechanistically, PLB promoted HMBOX1 expression, leading to inactivation of PI3K/Akt-mTOR of liver cancer cells. Moreover, PLB also inhibited tumor formation in a xenograft transplantation model via PI3K/Akt/mTOR signaling. Collectively, our results suggested that HMBOX1 played a key role in PLB-induced inhibition of HCC growth through PI3K/Akt/mTOR signaling pathway.

AIMS:Breast cancer has become the number 1 killer threatening women's health. In recent years, glycosylation modification has played an increasingly important role in tumor progression. The aim of this study was to explore the key genes that may be involved in glycosylation modification, establish prognostic models, and further explore their biological functions. METHODS:Using data from TCGA and GEO databases, differentially expressed genes (DEGs) were identified. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to characterize the functions of the DEGs. LASSO regression analysis was performed to narrow down hub genes. Additionally, single-cell analysis, protein-protein interaction (PPI) network analysis, immune correlation analysis, drug sensitivity analysis, and molecular docking were carried out to investigate the functions of these hub genes. RESULTS:Initially, we identified 110 differentially expressed prognostic genes, among which 89 were potentially associated with glycosylation modification. Enrichment analysis revealed their involvement in oxytocin signaling, chemical carcinogen-DNA adduct formation, and C-type lectin receptor pathways. LASSO regression (Least Absolute Shrinkage and Selection Operator) analysis further refined the selection to 24 hub genes, which exhibited specific genetic interactions. Notably, the expression levels of these genes showed significant associations with various immune cells. Drug sensitivity analysis of the hub genes highlighted methotrexate as a potential therapeutic candidate. Finally, molecular docking demonstrated strong binding affinities between the target receptors and ligands. CONCLUSIONS:In conclusion, we screened glycosylation-related Hub genes, constructed prognostic models, explored their biological functions, and proposed new insights for diagnosing and treating breast cancer.