This study aimed to construct a novel model and validate its predictive power in non-esophageal squamous cell carcinoma (NESCC) patients.

This retrospective study included 151 patients between October 2006 and September 2016. The LASSO Cox and Random Survival Forest (RSF) models were developed with the help of hematological biomarkers and clinical characteristics. The concordance index (C-index) was used to assess the prognostic power of the LASSO Cox model, RSF model, and TNM staging. Based on the risk scores of the LASSO Cox and RSF models, we divided patients into low-risk and high-risk subgroups.

We constructed two models in NESCC patients according to LASSO Cox regression and RSF models. The RSF model reached a C-index of 0.841 (95% CI: 0.792-0.889) in the primary cohort and 0.880 (95% CI: 0.830-0.930) in the validation cohort, which was higher than the C-index of the LASSO Cox model 0.656 (95% CI: 0.580-0.732) and 0.632 (95% CI: 0.542-0.720) in the two cohorts. The integrated C/D area under the ROC curve (AUC) values for the LASSO Cox and RSF models were 0.701 and 0.861, respectively. In both two models, Kaplan-Meier survival analysis and the estimated restricted mean survival time (RMST) values indicated that the low-risk subgroup had a better prognostic outcome than the high-risk subgroup (p < 0.05).

The RSF model has better prediction power than the LASSO Cox and the TNM staging models. It has a guiding value for the choice of individualized treatment in patients with NESCC.

Non-small cell lung cancer (NSCLC) is a fatal disease, and radioresistance is an important factor leading to treatment failure and disease progression. The objective of this research was to detect radioresistance-related genes (RRRGs) with prognostic value in NSCLC.

The weighted gene coexpression network analysis (WGCNA) and differentially expressed genes (DEGs) analysis were performed to identify RRRGs using expression profiles from TCGA and GEO databases. The least absolute shrinkage and selection operator (LASSO) regression and random survival forest (RSF) were used to screen for prognostically relevant RRRGs. Multivariate Cox regression was used to construct a risk score model. Then, Immune landscape and drug sensitivity were evaluated. The biological functions exerted by the key gene LBH were verified by in vitro experiments.

Ninety-nine RRRGs were screened by intersecting the results of DEGs and WGCNA, then 11 hub RRRGs associated with survival were identified using machine learning algorithms (LASSO and RSF). Subsequently, an eight-gene (APOBEC3B, DOCK4, IER5L, LBH, LY6K, RERG, RMDN2 and TSPAN2) risk score model was established and demonstrated to be an independent prognostic factor in NSCLC on the basis of Cox regression analysis. The immune landscape and sensitivity to anti-tumour drugs showed significant disparities between patients categorized into different risk score subgroups. In vitro experiments indicated that overexpression of LBH enhanced the radiosensitivity of A549 cells, and knockdown LBH reversed the cytotoxicity induced by X-rays.

Our study developed an eight-gene risk score model with potential clinical value that can be adopted for choice of drug treatment and prognostic prediction. Its clinical routine use may assist clinicians in selecting more rational practices for individuals, which is important for improving the prognosis of NSCLC patients. These findings also provide references for the development of potential therapeutic targets.

The clinical relevance of T cell-related molecules at single-cell resolution in laryngeal cancer (LC) has not been clarified.

Three LC tissues and matching adjoining normal tissues from the hospital were used to perform 10X single-cell RNA sequencing. Hub T cell-related genes (TCRGs) were detected by applying ten machine learning (ML) techniques based TCGA and GEO databases, which were also utilized to create a prediction model (TCRG classifier) and a multicenter validation model. Lastly, we conducted a comprehensive analysis of the TCRG's correlation with immunological properties.

The analysis of single-cell RNA-seq data revealed that T cells are the primary components of the tumor microenvironment (TME), are significantly involved in cell differentiation pathways, and play a considerable role in intercellular communication. Based on 10 ML approaches, TCRG classifier were identified to develop and validate. The TCRG classifier exhibited excellent prognostic values with a mean C-index of 0.66 in six cohorts, serving as an independent risk factor (p < 0.01). Additionally, the TCRG exhibited a significant relationship with immune score, immune cell infiltration, immune-associated pathways, immune checkpoint inhibitors, human leukocyte antigen, and immunogenicity. Lastly, IPS, TCIC, TIDE, and IMvigor210 cohort analysis illustrated that the immunotherapy response may be accurately predicted using TCRG.

A TCRG classifier is an excellent resource for predicting a patient's prognosis, potentially guiding the preservation of laryngeal function, and identifying patients who may have a positive response to immunotherapy, which might have profound effects on therapeutic practice.

Rectal adenocarcinoma (READ) involves the dysregulated expression of alpha 2,8-Sialyltransferase1 (ST8Sia1) although its role during READ's progression is unclear.

The mRNA level of ST8Sia1 was analyzed based on The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Tumor Immune Estimation Resource (TIMER) 2.0. Furthermore, the prognostic and significance of ST8Sia1 in READ was assessed through Kaplan-Meier curve, univariate, multivariate Cox regression, and receiver operating characteristic (ROC) methods. The role of ST8Sia1 in the READ immune microenvironment was explored using ESTIMATE analysis and TIMER databases. Furthermore, the expression of ST8Sia1 in tissues was analyzed using real-time quantitative polymerase chain reaction (RT-qPCR), western blotting (WB), and immunohistochemistry (IHC). Perforin and Granzyme B secretion by CD8+ T cells, as well as tumor cell apoptosis, were detected after co-culturing CD8+ T cells with READ tumor cells and ST8Sia1-overexpression (ST8Sia1-OE) tumor cells. Furthermore, we examined the interaction between ST8Sia1 and TGF-β1 in READ cells.

ST8Sia1 exhibited excellent diagnostic capability for READ, with positive correlations to immune response and negative correlations to tumor purity. Increased levels of perforin and Granzyme B from CD8+ T cells were observed in vitro, enhancing tumor cell apoptosis. ST8Sia1 interacts with TGF-β1, mediating its inhibitory effects on READ development.

ST8Sia1 is a potential diagnostic biomarker and therapeutic target for READ, enhancing CD8+ T cell function and possibly improving patient outcomes through cellular immunotherapy.

Inflammation plays a critical role in prostate cancer (PCa) pathophysiology, yet the diagnostic value of specific inflammatory markers remains unclear. This study evaluates the association between circulating and tissue inflammatory markers with PCa presence and their potential as biomarkers for risk stratification. This prospective study analyzed serum and prostate biopsy samples from 60 patients with PCa and 22 cancer-free controls. Concentrations of inflammatory markers, including IL-2, IL-4, IL-10, IL-13, IL-33, Oncostatin M, TNFα, PDGF-BB, and TREM-1, were measured using Luminex technology. Statistical analyses included the Mann-Whitney test, logistic regression, and ROC curve analysis to assess differences and diagnostic performance. PCa patients exhibited significantly higher serum levels of IL-2 (p = 0.001), IL-10 (p < 0.001), IL-33 (p < 0.001), Oncostatin M (p = 0.018), and TNFα (p = 0.017) compared to controls. In contrast, biopsy tissue levels of IL-4 (p < 0.001), IL-10 (p < 0.001), IL-13 (p = 0.004), Oncostatin M (p = 0.012), PDGF-BB (p = 0.039), and TREM-1 (p = 0.013) were significantly lower in PCa patients, suggesting an inverse association. IL-10 (inverse) and IL-4 (inverse) in biopsy tissue showed high specificity in ROC analysis (AUC = 0.788 and 0.804, respectively), while IL-2 and IL-33 in serum were positively associated with PCa risk. This study suggests that IL-4, IL-10, and IL-13 in biopsy tissue may serve as biomarkers of a protective effect, while elevated IL-2 and IL-33 in serum are associated with an increased risk of PCa. These findings highlight the potential of inflammatory markers in PCa risk stratification, warranting further investigation in larger cohorts.

This was a pooled analysis of data from weekly vinorelbine (VNR) treatment arms of four individual open-label, phase II studies to assess and refine the efficacy and tolerance of weekly oral VNR in a larger cohort of patients with advanced NSCLC.

All patients included in this pooled analysis received oral VNR at the dose of 60 mg/m2 weekly at cycle 1 (3-week cycle), followed by an increase to 80 mg/m2 weekly for subsequent cycles until disease progression or toxicity. Efficacy was based on objective response rate (ORR), progression-free survival (PFS), and disease control rate (DCR).

A total of 247 patients were included. The ORR and DCR were 8.9% and 57.5% respectively, median PFS and OS were 3.3 and 8.5 months, respectively. Less than half (40.7%) of patients reported ≥1 serious AE (regardless of causality), with 12.3% reporting ≥1 treatment-related serious AE (grade ≥3: 11.1%). The most reported grade ≥3 AEs were neutropenia (17.6%), fatigue (5.8%), and decreased appetite (4.9%).

This pooled analysis showed that weekly oral VRN is a valid option, with an acceptable safety profile, in this population of patients with advanced NSCLC, confirming results from previous individual studies.

Several studies have shown that combining immune checkpoint inhibitors (ICIs) with antiangiogenic tyrosine kinase inhibitors is effective for solid tumors, including esophageal squamous cell carcinoma (ESCC). However, most of these studies were focused on immunotherapy-naive patients. This retrospective real-world study offers insights into the efficacy and safety of combining anlotinib with ICIs in locally advanced/metastatic ESCC patients who progressed on prior ICI.

We retrospectively analyzed the efficacy and safety of anlotinib plus PD-1 inhibitor in locally advanced/metastatic ESCC patients who had progressed on PD-1 inhibitor. Efficacy was assessed according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). The primary endpoints were the objective response rate (ORR) and disease control rate (DCR), while secondary endpoints were safety, overall survival (OS) and progression-free survival (PFS). Baseline characteristics and adverse events (AEs) were documented throughout the study.

Between July 2020 and March 2022, 29 eligible patients were included in the final analysis, with 23 (79.3%) having previously undergone resection for ESCC. Of these 29 patients, 8 (27.6%) received first-line systemic therapy, 20 (69.0%) received second-line therapy, and 1 patient (3%) received third-line therapy. At the data cutoff, the ORR was 31.0%, and the DCR was 86.2%, with 9 patients achieving partial response (PR), 16 patients with stable disease (SD) and 4 patients with disease progression (PD). The median PFS was 5.33 months (95% CI: 4.28-6.38), and the median OS was 10.37 months (95% CI: 6.26-14.46). All patients experienced treatment-related adverse events (TRAEs), with anemia and lymphopenia being the most common. Only 2 patients (6.9%) experiencing grade 3-4 lymphopenia. All AEs were managed with symptomatic treatment and no treatment-related deaths occurred.

The combination of anlotinib and a PD-1 inhibitor demonstrated promising antitumor efficacy and manageable toxicity in patients with locally advanced/metastatic ESCC who progressed on prior ICI. This regimen represents a feasible and well-tolerated treatment option for this patient population.

NCT04984096.

Photodynamic therapy (PDT) using photosensitizer (PS)-integrated covered self-expandable metallic stents (SEMS) is proposed a new therapeutic approach for the treatment of palliative malignancies; however, the currently hydrophobic PS reduces the photoreactive effect, which leads to aggregation with low water solubility. In here, an aluminum (III)-phthalocyanine chloride tetrasulfonic acid (Al-PcS4)-integrated silicone-covered self-expanding catheter was successfully fabricated to perform localized PDT. The ratio of MeOH and Al-PcS4 concentrations was optimized to achieve PS coating uniformity. The photodynamic activity of the Al-PcS4-integrated silicone membrane was evaluated through laser exposure on membrane-layered tumor cell lines, tumor xenograft-bearing mice. PDT with the Al-PcS4-integrated membrane successfully generated sufficient cytotoxic singlet oxygen, inducing cell death in the esophageal cancer cell lines. PDT-treated tumor xenograft-bearing mice undergo apoptotic cell death and showed significant tumor regression. Localized PDT using an Al-PcS4-integrated silicone-covered self-expanding catheter was technically successful in the rabbit esophagus without severe complications. Based on the endoscopy, esophagography, histology, and immunohistochemistry, our study verified that localized PDT using the Al-PcS4-integrated silicone-covered self-expanding catheter was effective and safe to evenly induce tissue damage. Al-PcS4-integrated silicone-covered self-expanding catheter has substantial potential for the minimally invasive local therapy in malignant esophageal cancer.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) may lead to drug resistance, and the underlying mechanism may involve histologic transformations to small cell carcinoma (SCC), squamous cell carcinoma (SqCC), and sarcomatoid carcinoma (SC). Although there are reports regarding these transformations, comprehensive analyses are limited.

A total of 233 patients with primary lung adenocarcinoma treated with EGFR-TKIs were reviewed. Among them, 26 patients (11.1 %) showed histologic transformation.

Eleven patients (42.3 %) showed SCC and SqCC transformations respectively, and four patients (15.4 %) showed SC transformation. The median time from TKI initiation to transformation was 19.8 months (6.8-51.4) for SCC, 45.3 months (2.4-101.5) for SqCC, and 11.8 months (6.8-15.7) for SC. The median overall survival (OS) was 41.8 months (12.5-78.9), 72.6 months (18.8-112.7), and 23.7 months (17.4-34.4), respectively. The survival from transformation was 12.3 months (2.1-28.3), 16.9 months (0.7-43.2), and 11.4 months (1.6-23.5), respectively. The most common mutations were TP53, PTEN, and RB1 in SCC; TP53 and RB1 in SqCC; and TP53 and KMT2D in SC. SC transformation had the worst OS, followed by SCC and SqCC (p < 0.001). This prognosis difference was also reflected in the time to transformation after EGFR-TKI treatment (p = 0.005). However, survival after transformation was not associated with tumor subtypes (p = 0.536).

The analysis of mutation profiles and survival outcomes revealed that the transformation subtype affects prognosis. Additionally, the time taken to undergo transformation is critical for patient outcomes.

An emerging issue is that patients are prone to become resistance to epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) which are the first- line treatment for EGFR-mutated non-small cell lung cancer (NSCLC) after approximately 10 months of drug administration. Interestingly, metabolic dysregulation occurs simultaneously with acquired EGFR-TKI resistance in certain NSCLC cell lines.

We aimed to investigate whether a natural product, halofuginone (HF), could overcome NSCLC resistance to EGFR-TKIs by influencing metabolism.

In our study, the combination of HF and EGFR-TKI exhibited synergistic cytotoxicity compared to EGFR-TKI monotherapy. The underlying mechanism is that HF promotes the degradation of SP1 protein and decreases the expression of phosphatidylserine transcarbamoylase 1 (PSAT1), which leads to defects in the de novo synthesis of Serine/Glycine and cell death.

HF is a promising natural product for overcoming NSCLC resistance to third-generation epidermal growth factor receptors-TKIs.

Small intestinal adenocarcinomas (SIAs) are associated with predisposing conditions, including inflammatory bowel disease (IBD) and celiac disease, but also genetic syndromes such as Lynch syndrome (LS) and familial adenomatous polyposis (FAP). This nationwide cohort study investigated the incidence of genetic and non-genetic predisposing conditions in SIA and their influence on tumor characteristics and clinical features. Data were obtained from the Netherlands Cancer Registry. The incidence, characteristics, and clinical features per predisposing condition were analyzed in 2697 SIA patients diagnosed from 1999 through 2019. Of all SIA patients, 5.6% were known to have a genetic predisposing syndrome, of whom 4.0% had LS and 1.6% had a polyposis syndrome. In addition, 6.8% of SIA patients had a non-genetic predisposing condition: 3.9% IBD and 2.9% celiac disease. SIAs of patients with such predisposing syndromes or conditions were diagnosed at a younger age and earlier stage and affected the duodenum less often as compared to sporadic SIA patients. Both genetic and non-genetic predisposing conditions were associated with significantly better overall survival (OS) compared to sporadic SIA: sporadic SIA (median OS: 13.0 months, 95% CI: 11.8-14.2), LS (213.1 months, 99.3-NA), polyposis syndromes (61.3 months, 19.7-NA), IBD (29.5 months, 20.3-69.8), and celiac disease (50.4 months, 24.6-124.7). This nationwide cohort study shows significant differences between SIA with and without predisposing conditions and highlights the need for research on underlying molecular mechanisms to improve outcomes of SIA patients.

Microtubules, as dynamic regulators in many cellular processes, remain pivotal targets in cancer chemotherapy. Among the structural motifs explored, the benzimidazole scaffold has emerged as a privileged heterocyclic ring system in the development of potent therapeutic agents, owing to its versatility and pharmacological relevance. This review critically examines the synthesis, anticancer activity, structure-activity relationships (SAR), and tubulin polymerization inhibitory properties of diverse benzimidazole derivatives. In addition, various synthetic strategies and innovative approaches for generating benzimidazole based analogs with enhanced cytotoxic profiles are highlighted. Recent findings underscore the potential of benzimidazole derivatives as promising tubulin polymerization inhibitors, contributing significantly to the discovery of next-generation anticancer agents.

Intraoperative radiotherapy (IORT) has been used as a novel therapeutic alternative for breast-conserving surgery (BCS) in patients with breast cancer. However, the long-term outcomes and safety of IORT in patients with breast cancer remain incompletely understood. Therefore, the present study aimed to explore the long-term outcomes of IORT following BCS, focusing on the oncological outcomes and cosmetic consequences compared with postoperative RT (PORT) in patients with breast cancer. Patients with early-stage breast cancer who underwent BCS followed by IORT or PORT between January 2016 and October 2020 at the Research Institute of General Surgery, Jinling Hospital, Nanjing Medical University (Nanjing, China), were retrospectively reviewed. After screening, a total of 59 patients were included in the present study and divided into two groups according RT records as follows: The IORT group (n=21) and the PORT group (n=38). The clinical data of all patients, including surgical and RT complications, cosmetic grading and scoring, and other events, were collected and retrospectively analyzed. No significant difference was observed in terms of the mean follow-up time in the IORT (5.89±1.57 years) and PORT (6.09±1.60 years) groups (P>0.05). Compared with PORT, IORT showed non-inferior therapeutic efficacy, with no significant differences in postoperative complications (surgical site infection and chronic pain; P>0.05). Notably, the IORT group achieved superior cosmetic outcomes, with 95.2% (20/21) of patients achieving a rating of excellent/good vs. 44.7% (17/38 patients) in the PORT group (P<0.001), alongside higher median cosmetic scores at all postoperative intervals (P<0.01). IORT also reduced healthcare utilization, shortening hospitalization by 23.8 days (12.1±5.1 vs. 35.9±3.5 days; P<0.001) and lowering costs significantly (33,117.98±6,281.17 vs. 77,789.55±7,000.90 CNY; P<0.001). These findings suggest that IORT offers comparable safety, improved cosmesis and greater cost-effectiveness than PORT, supporting its integration into clinical practice for eligible patients.

Ovarian cancer, ranking fifth in cancer mortality, presents a significant therapeutic challenge. The immunomodulatory functions of CD38in epithelial ovarian cancer (EOC) and its influence on the tumor microenvironment (TME) remain poorly understood.

Public datasets, RT-qPCR and immunohistochemistry (IHC) were used to analyze CD38 expression and clinicopathological features in EOC. Gene manipulation techniques were employed to elucidate its functions, while integrated IHC and bioinformatics were conducted to assess its involvement in immune/stromal infiltration. Immune-related functions of CD38 were explored using GO, KEGG analysis and TIP database. TIDE algorithm was employed to predict the correlation between CD38 and immune checkpoint blocking responsiveness. CD38 inhibitor efficacy was evaluated in an EOC mouse model, with flow cytometry monitoring cellular changes. The involvement of CD38 in the PI3K-AKT and IL-6 signaling pathways was evaluated using RT-qPCR, western blot, and publicly datasets.

CD38 is significantly upregulated in EOC, influencing the cell proliferation and metastasis. It regulates the PI3K-AKT and IL-6 signaling pathways, thereby increasing tumor malignancy. CD38 is also upregulated in immune and stromal cells, affecting TME remodeling by facilitating immune cell and CAF infiltration, impeding T cell recognition of tumor cells, and enhancing CAF-tumor cell communication. Additionally, CD38 correlates with multiple immune checkpoint molecules. Notably, CD38 inhibitor therapy inhibited effectively EOC progression and modulates immune responses.

Elevated CD38 expression is associated with EOC progression, TME remodeling, and immune response modulation. Thus, CD38 could be a promising target for ovarian cancer immunotherapy.

Protein post‑translational modifications (PTMs) play crucial roles in various life activities and aberrant protein modifications are closely associated with numerous major human diseases. Ubiquitination, the first identified protein modification system, involves the covalent attachment of ubiquitin molecules to lysine residues of target proteins. UFMylation, a recently discovered ubiquitin‑like modification, shares similarities with ubiquitination. The precursor form of ubiquitin fold modifier 1 (UFM1) undergoes synthesis and cleavage by UFM1‑specific protease 1 or UFM1‑specific protease 2 to generate activated UFM1‑G83. Subsequently, UFM1‑G83 is activated by a specific E1‑like activase, UFM1‑activating enzyme 5. UFM1‑conjugating enzyme 1 and an E3‑like ligase, UFM1‑specific ligase 1, recognize the target protein and facilitate UFMylation, leading to the degradation of the target protein. Current knowledge regarding UFMylation remains limited. Previous studies have demonstrated that defects in the UFMylation pathway can result in embryonic lethality in mice and various human diseases, highlighting the critical biological functions of UFMylation. However, the precise mechanisms underlying UFMylation remain elusive. This present review aimed to summarize recent research advances in UFMylation, with the aim of providing novel insights and perspectives for future investigations into this essential protein modification system.

Urologic malignancies, encompassing cancers of the kidney, bladder, and prostate, represent approximately 25 % of all cancer cases. Recent advances have enhanced our understanding of PVT1's crucial functions. Long noncoding RNAs influence both the onset and development of cancer, as well as epigenetic alterations. Recent findings have focused on PVT1's mechanism of action across several malignancies, particularly urologic cancers. Understanding the various functions of PVT1 linked to cancer is necessary for the development of cancer detection and treatment when PVT1 is dysregulated. Furthermore, recent advancements in genomic and epigenetic research have elucidated the complex regulatory networks that control PVT1 expression. Comprehending the intricate role of PVT1 Understanding the complex function of PVT1 in urologic cancers has substantial clinical implications. Here, we summarize some of the most recent findings about the carcinogenic effects of PVT1 signaling pathways and the possible treatment strategies for urological malignancies that target these pathways.

Objective  The aim of this study was to compare the sensitivity and prostate cancer detection rate of magnetic resonance (MR) in-bore biopsy with transrectal ultrasound (TRUS) guided systematic biopsy. We also compared the cancer detection rate of the combined MR in-bore and TRUS-guided systematic biopsy with the TRUS-guided biopsy only approach. Materials and Methods  In this prospective study, 61 consecutive patients with prostate-specific antigen (PSA) ≥ 3 ng/mL and Prostate Imaging Reporting and Data System (PI-RADS) score ≥4 were recruited between July 2017 and January 2020. One patient with prior prostate surgery was excluded. Among the remaining 60 patients, 30 underwent MR in-bore biopsy followed by systematic biopsy (study arm A) and 30 underwent systematic biopsy only (study arm B). Results  The mean PSA range of study population ( n  = 60 patients) was 4.2 to 72.7 ng/mL. Twenty-seven patients had a PI-RADS score of 4, and 33 patients had a PI-RADS score of 5. Among 60 patients, 30 had prostate carcinoma on biopsy, of which 18 were clinically significant prostate cancers (csPCa). In study arm A, TRUS-guided systematic biopsy had a lower sensitivity (0.9) for detection of csPCa compared with MR in-bore biopsy (1.0) with overdetection of insignificant cancers (sensitivity: 0.89 vs. 0.56). TRUS-guided biopsy yielded 112 positive cores out of 360, whereas MR in-bore biopsy yielded 15 positive cores out of 30 (31.1 vs. 50%; p  = 0.03). On comparison of study arms A and B, the diagnostic yield for detection of both prostate cancer and csPCa were high in study arm A (60 vs. 40%, and 33.3 vs. 26.7%, respectively) Conclusion  MRI in-bore targeted biopsy had a greater sensitivity to detect csPCa with fewer number of biopsy cores and lower sensitivity to detect insignificant cancers compared with systematic biopsy. Systematic biopsies were associated with overdetection of clinically insignificant cancers.

Pancreatic cancer remains one for the most aggressive cancer worldwide, with pancreatic ductal adenocarcinoma being the most common malignant pancreatic lesion, associated with poor prognosis. While surgical resection is the only curative treatment, only a minority of patients is eligible for surgery due to its diagnosis at advanced stages. Therefore, strategies for early detection of pancreatic cancer are needed. This article aims to provide a state-of-the-art review of the most common conditions associated to an increased risk of pancreatic cancer. Conditions linked to risk of pancreatic cancer development include certain pancreato-biliary anatomical variants, intraductal papillary mucinous neoplasms, mucinous cystic neoplasm, and familial pancreatic cancer with specific genetic mutations. Early imaging signs of pancreatic cancer can also be incidentally encountered on CT or MRI performed for other indications and they should be promptly recognized by the radiologists in order to avoid delays in the diagnosis. The features include focal pancreatic atrophy, contour deformity, dilation of the main pancreatic duct (MPD), changes in the caliber of the MPD, abrupt interruption of the MPD, and biliary tree dilation. MRI with the adoption of abbreviated protocols has been increasingly evaluated for the follow-up of cystic lesions. Although screening of the general population is not recommended due to the low incidence and high costs, surveillance with MRI can be considered in selected high-risk individuals.

Metastasis remains the leading cause of cancer-related mortality, with a persistently poor prognosis for metastatic cancer patients despite extensive therapeutic efforts. Circulating tumor cells (CTCs), which detach from primary tumors and enter the bloodstream, can establish distant metastatic sites. These CTCs often form heterotypic clusters with white blood cells, especially neutrophils, through various interaction mechanisms, including intercellular adhesion, cytokine secretion, protease release, and the formation of neutrophil extracellular traps (NETs). These interactions enhance CTCs survival, proliferation, invasion, and transendothelial migration while simultaneously remodeling premetastatic niches and the tumor microenvironment. Consequently, pharmacologically disrupting CTC‒neutrophil crosstalk represents a promising strategy to curb metastatic spread and improve clinical outcomes. Recent breakthroughs in nanotechnology-based drug delivery systems have shown considerable potential in antimetastatic therapies, offering significant advantages over conventional treatments, which are often associated with severe side effects and limited efficacy. This review systematically explores nanoengineered strategies targeting CTC‒neutrophil interactions, addresses the current limitations and outlines future directions for developing clinically translatable nanotherapeutics.

This study aimed to investigate the prognostic significance of SH3BP5-AS1 in non-small cell lung cancer (NSCLC) patients, and also to uncover its function in the progression of NSCLC.

100 NSCLC patients were recruited in this study. SH3BP5-AS1 was measured by RT-qPCR. The prognostic significance of SH3BP5-AS1 in NSCLC progression was appraised utilizing the Kaplan-Meier and Cox regression test. CCK-8 was used to detect the proliferative viability of NSCLC cells. The migratory and invasive capabilities of NSCLC cells were evaluated by Transwell assay. The interplay between SH3BP5-AS1 and miR-424-5p was verified by luciferase reporter assay and ENCORI database. The potential target genes of miR-424-5p were inspected by means of bioinformatics analysis.

A reduced SH3BP5-AS1 was manifested in tissues of NSCLC patients and tumor cells. Compared with patients showing SH3BP5-AS1 low-expression, those with SH3BP5-AS1 high-expression possessed a more favorable progression-free survival time. SH3BP5-AS1 might function as an autonomous prognostic biomarker for NSCLC. Upregulation of SH3BP5-AS1 suppressed the proliferation, migration and invasion of NSCLC cells. MiR-424-5p was a downstream target miRNA of SH3BP5-AS1, and luciferase reporter assays verified that SH3BP5-AS1 and miR-424-5p interact. In NSCLC patient tissues, miR-424-5p was upregulated and it exhibited an inverse correlation with SH3BP5-AS1. Elevation of miR-424-5p neutralized the inhibitory effect of SH3BP5-AS1 overexpression on the proliferation, migration, and invasion abilities of NSCLC cells.

SH3BP5-AS1 is involved in NSCLC development by targeting its downstream target miRNA miR-424-5p, and it is a latent prognostic indicator for NSCLC.

Sorafenib is the main treatment for advanced hepatocellular carcinoma (HCC), but drug resistance limits its effectiveness. Evidence increasingly indicates that, in addition to targeting tyrosine kinases, sorafenib also induces ferroptosis. However, current studies have not fully clarified the relationship between ferroptosis and sorafenib treatment sensitivity. Our bioinformatics analysis identified that SIX Homeobox 2 (SIX2), known for maintaining cellular stemness via the Wnt signaling pathway, was significantly upregulated in sorafenib-resistant tissues. Overexpression and knockdown experiments revealed that altering SIX2 expression affected HCC cell sensitivity to sorafenib and involved the ferroptosis pathway, suggesting a regulatory role for SIX2 in ferroptosis. RNA sequencing and CUT&Tag analysis showed that SIX2 directly regulated methyltransferase 9 (METTL9) expression. Co-immunoprecipitation (Co-IP) assays confirmed that METTL9 bound to SLC7A11, enhancing its stability and reducing degradation, thus regulating ferroptosis. Importantly, the role of SIX2 in ferroptosis operated independently of the classical glutathione peroxidase 4 (GPX4) pathway. In vitro studies further supported these findings, demonstrating that SIX2 knockdown increased sorafenib-induced ferroptosis in HCC, while METTL9 overexpression largely counteracted the effects of SIX2 knockdown. In mouse models, overexpression of SIX2 increased tumor resistance to sorafenib. Our findings suggest that modulating the ferroptosis pathway through SIX2 could enhance sorafenib sensitivity. This study provides the first evidence that SIX2 influences ferroptosis via the METTL9-SLC7A11 axis, thereby sensitizing HCC cells to sorafenib. Reducing SIX2 expression could thus represent a promising strategy to improve the efficacy of sorafenib in advanced HCC.

The transcriptional regulation of olfactory receptors (ORs) plays a critical role in various biological processes, and has recently been considered a potential therapeutic target for cancer treatment. Esophageal cancer (EC) is a highly invasive neoplasm with dismal prognosis, but the specific roles of ORs in EC remain largely unexplored. Here, we developed a comprehensive workflow to identify potential functional olfactory receptor family 51 subfamily B member 5 (OR51B5) and demonstrated that OR51B5 locus acted as a key spatial element contributing to the progression of esophageal cancer. Moreover, we showed that the CTCF-EZH2 enhanced the trimethylation of lysine 27 of histone H3 (H3K27me3) and increased repressive and closed chromatin state at the OR51B5 promoter region. Subsequently we demonstrated that closed chromatin impaired the entry of RNA polymerase II and inhibited the transcription of OR51B5, thereby causing N-Ras activation and promoting tumor cell proliferation and metastasis. Our study provides an alternative workflow for discovering critical regulatory sites for control tumorigenesis, and reveals a novel OR51B5 triggering mechanism underlying esophageal cancer progression.

Ovarian cancer (OC) is a highly aggressive malignancy characterized by a complex immune microenvironment. B cells, essential components of immunological regulation, have been implicated in the progression of ovarian cancer. However, the precise mechanisms by which B cells and immune molecules influence ovarian cancer risk remain poorly understood.

This study employed single-cell RNA sequencing (scRNA-seq) to analyze peripheral blood mononuclear cells (PBMCs) from ovarian cancer patients and healthy donors. Differential gene expression analysis identified CD14 as a critical gene in B cells. Mendelian randomization (MR) analysis, using exposure data from eQTL and pQTL databases, was performed to evaluate the association between CD14 and ovarian cancer risk. Mediation analysis was conducted to assess the role of CD80 on myeloid dendritic cells in mediating the relationship between CD14 and ovarian cancer.

The analysis demonstrated that CD14 expression was significantly downregulated in B cells from ovarian cancer patients compared to healthy donors. MR analysis revealed a significant association between elevated CD14 expression and reduced ovarian cancer risk. Mediation analysis indicated that CD80 mediated 26.2% of this effect.

These findings highlight CD14 as a key regulator of ovarian cancer risk, with CD80 serving as a mediator of the immune response in this context. This study provides insights into potential immune modulation strategies for ovarian cancer therapy.

Senescence, defined by the cessation of cell proliferation, plays a critical and multifaceted role in breast cancer progression and treatment. Senescent cells produce senescence-associated secretory phenotypes (SASP) comprising inflammatory cytokines, chemokines, and small molecules, which actively shape the tumor microenvironment, influencing cancer development, progression, and metastasis. This review provides a comprehensive analysis of the types and origins of senescent cells in breast cancer, alongside their markers and detection methods. Special focus is placed on pharmacological strategies targeting senescence, including drugs that induce or inhibit senescence, their molecular mechanisms, and their roles in therapeutic outcomes when combined with chemotherapy and radiotherapy. By exploring these pharmacological interventions and their impact on breast cancer treatment, this review underscores the potential of senescence-targeting therapies to revolutionize breast cancer management.

The most prevalent cause of cancer-related death in China and across the globe is lung adenocarcinoma (LUAD). Telomere shortening (TS) has been found to contribute to the development of LUAD. Therefore, our aim is to investigate the impact of telomere-related genes (TRGs) on immunotherapy and clinical prognosis prediction in LUAD.

TRGs were obtained from TelNet, while RNA-seq and clinical information were retrieved from the GEO and TCGA databases. TelNet preserves a series of genes known to be engaged in telomere maintenance and also provides information on the type of telomere maintenance mechanism in which the gene is involved. Data pertinent to RNA sequencing and clinical parameters were accessed from two widely-accessed electronic repositories- the GEO and TCGA databases, respectively. We conducted univariate Cox regression analysis in order to recognize prognostic TRGs and employed multivariate Cox regression analysis to develop a risk model for these TRGs. The patients were stratified into high-risk and low-risk groups based on the first quartile of the risk score. The predictive ability and stability of the model were subsequently verified through Kaplan-Meier analysis, ROC curve, and C-index. We investigated the immune landscapes of different risk groups and predicted their responses to immunotherapy. Lastly, we evaluated the sensitivity of different groups to commonly used chemotherapeutic and targeted drugs through drug sensitivity analysis.

Univariate Cox analysis identified 12 prognostic TRGs, while a signature consisting of 4 prognostic TRGs was constructed through multivariate Cox analysis. Survival analysis indicated a significantly shorter survival time in the high-risk group. The predictive immunotherapy analysis suggested that patients in the high-risk group may have a more favorable response to immunotherapy. Finally, we identified 28 appropriate chemotherapeutic and 51 targeted drugs for different patient groups.

The study has successfully developed a prognostic model for LUAD prediction that takes into account TRGs and predicts both prognosis and response to immunotherapy.

Lymph node (LN) metastasis of gastric cancer (GC) is one of the important pathways of GC metastasis, indicating the clinical staging and prognosis of patients. To investigate the underlying mechanism during the process of GC-induced LN metastasis, 7 pairs of GC tissues, paracancerous (PC) tissues, GC-positive LN (LN.P) and GC-negative LN (LN.N) tissues from GC patients with homogeneity were selected for RNA sequencing (RNA-seq) analysis. Tensin 4 (TNS4) was screened out and found to be significantly upregulated in LN.P tissues and closely related with the characteristics of GC. In vitro and in vivo experiments demonstrated that knockdown of TNS4 could significantly inhibit LN metastasis of GC cells and activation of fibroblastic reticular cells (FRCs) in LNs, thus inhibiting LN expansion induced by tumor cell invasion. Moreover, TNS4 was found to be interacted with integrin beta 1 (ITGB1) on FRCs, thereby affecting the binding of transforming growth factor β1 (TGF-β1) to ITGB1 and subsequently regulating downstream signaling molecules, and supporting the GC cell-induced LN metastasis.

 The tumor microenvironment and biomarkers play a pivotal role in breast cancer research, yet there remains a pressing need for effective biomarkers. This study focuses on identifying a novel IGKC+ T Cell subpopulation and its related biomarkers to pave the way for innovative targeted therapies and improved clinical outcomes.

We first performed single-cell RNA sequencing (scRNA-seq) analysis to characterize immune cell heterogeneity within the tumor microenvironment, leading to the identification of series cell subpopulation. Then, by performing univariate analysis to correlate cell proportions with patient prognosis, we identified a novel IGKC+ T cell subpopulation. Next, we applied bulk RNA-seq deconvolution algorithms to estimate the abundance of this subpopulation across breast cancer cohorts. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were employed to identify genes associated with the IGKC+ T cell population. To pinpoint key regulatory genes, we applied machine learning algorithms. Based on the hub genes identified, we constructed a prognostic risk model and developed a nomogram to aid clinical decision-making. Immune infiltration patterns were further assessed in high- vs low-risk groups defined by the model. Finally, functional validation was performed through overexpression of BCL2L14 in vitro, and downstream signaling pathways were examined.

We identified the novel IGKC+ T cell subpopulation and core genes. Machine learning pinpointed BCL2L14, IGHD, MAPT-AS1, NT5DC4, and TNIP3 as key regulators of breast cancer progression in this subpopulation. The model stratified patients into high- and low-risk groups, with high-risk patients showing worse prognosis and weaker immune infiltration. Overexpression of BCL2L14 was experimentally demonstrated to accelerate breast cancer progression, linked to enhanced phosphorylation of the NF-κB pathway.

Our results underscore BCL2L14 as a potential driver within the novel T-cell subpopulation and a critical biomarker for breast cancer diagnosis. These findings provide a basis for developing advanced diagnostic tools and targeted therapies, which may ultimately enhance patient prognosis.

Experimental studies have shown that dietary isothiocyanates reduced cellular proliferative marker Ki-67 and increased apoptotic markers caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) in animals, but human data are lacking. The present study was to assess whether sulforaphane would stop/reverse the progression of bronchial histopathology, reduce the Ki-67 index, and/or increase caspase-3 and TUNEL indices in humans. A randomized clinical trial (NCT03232138) was conducted in former smokers. Forty-three subjects were randomly assigned to the placebo or the treatment with a potential daily dose of 95 μmol sulforaphane for 12 months. The endpoints were the changes in histopathology scores and Ki-67, caspase-3, and TUNEL indices in post- versus pretreatment bronchial biopsies. Thirty-seven participants (17 in the sulforaphane and 20 in the placebo group) completed the study. Supplementation of sulforaphane did not show significant impact on bronchial histopathology but significantly reduced the Ki-67 index with a 20% decrease in the sulforaphane group and a 65% increase in the placebo (P = 0.014). The difference was even greater in high-density (3+) positive Ki-67, with a 44% decrease in the sulforaphane group compared with a 71% increase in the placebo (P = 0.004). Higher bioavailability of sulforaphane was correlated with greater reduction of the Ki-67 index (P for trend = 0.019). Sulforaphane treatment had no impact on the caspase-3 or TUNEL index in bronchial biopsies. No severe adverse event was observed in the study participants. The findings of oral sulforaphane that significantly reduced the Ki-67 index in bronchial tissue support further development as a potential chemopreventive agent against lung cancer development. Prevention Relevance: High intake of cruciferous vegetables and their sulforaphane is associated with lower incidence of lung cancer in humans and animal models. This clinical trial has demonstrated that oral supplementation of sulforaphane for 12 months significantly reduced the Ki-67 index, a potential surrogate endpoint of biomarkers for lung cancer risk.

Multiple myeloma (MM), a malignant hematologic tumor characterized by the proliferation of monoclonal plasma cells, remains incurable with high relapse rates despite advances in treatment. Patient-derived xenograft (PDX) models have emerged as a promising tool for understanding MM's complex pathophysiology and testing therapeutic responses. In this study, we successfully developed PDX models from three patients with MM by subcutaneously engrafting their tumor cells into immunodeficient NCG mice. These models accurately mirrored the clinical drug responses of their corresponding patient cases, exhibiting similar drug sensitivities and resistance patterns. Omics profiling facilitated the alignment of PDX models with specific molecular subgroups identified in current MM research, enhancing the models' clinical relevance. The concordance between PDX models and clinical data confirms the utility of these models in simulating patient-specific responses and advancing personalized treatment strategies. This study validates the effectiveness of PDX models established by subcutaneous engraftment of tumor cells in replicating human disease and treatment responses, thus providing a robust platform for future personalized treatments and development of targeted interventions in Chinese MM patients.

Long non-coding RNAs (lncRNAs) have been evidenced to function as pivotal modulators in tumorigenesis. LncRNA SNHG25 is highly expressed in colorectal cancer (CRC), but its specific function in CRC has not been elucidated yet. The expression of SNHG25, miR-329-3p, and PPP2R2D was determined using qRT-PCR analysis and western blot analysis. The influence of the SNHG25/miR-329-3p/PPP2R2D axis on CRC progression was explored through in vitro assays including CCK-8, colony formation, wound healing, Transwell assays and in vivo orthotopic xenografts assay. The interaction between miR-329-3p and SNHG25 or PPP2R2D was examined by RNA pull-down, RIP, and luciferase reporter assays. SNHG25 presented high expression in CRC cell lines. Silencing of SNHG25 suppressed the malignant phenotypes of CRC cells in vitro and tumor growth in vivo. MiR-329-3p, which displayed low expression in CRC cells, was sponged by SNHG25. Downregulation of miR-329-3p reversed the inhibitory effects of SNHG25 silencing on CRC cell malignant behaviors. Additionally, PPP2R2D served as a miR-329-3p downstream target, whose expression was downregulated by overexpressing miR-329-3p. Importantly, overexpression of PPP2R2D rescued SNHG25 silencing-induced repression on CRC cell malignancy. SNHG25 plays a carcinogenic role in CRC via regulation of the miR-329-3p/PPP2R2D axis.

The online version contains supplementary material available at 10.1007/s10616-025-00753-3.

This study aims to demonstrate that the EN2 protein in cervical mucus may serve as a novel biomarker for screening endometrial cancer.

This study included 133 patients who were treated at Beijing Obstetrics and Gynecology Hospital. According to the pathological results of hysteroscopy endometrial biopsy, the patients were divided into endometrial cancer group (n = 55), endometrial atypical hyperplasia group (n = 16), benign lesion group (n = 28), and control group (n = 34). All patients collected cervical mucus before hysteroscopy, and the level of EN2 protein in cervical mucus was detected by ELISA in the four groups of patients. Nine patients who underwent surgical treatment for endometrial cancer were included, and endometrial cancer lesions and adjacent tissues without endometrial cancer infiltration were taken from the endometrial cancer lesions and cervical tissues. Fifteen patients who underwent hysterectomy for benign lesions were included, and endometrial and cervical tissues were taken from the endometrial cancer lesions and adjacent tissues without endometrial cancer infiltration. PT-PCR, immunohistochemistry, and WB were used to verify the expression differences of EN2 protein in cancerous lesions and endometrial tissues without endometrial infiltration, cervical tissues, and endometrial tissues without endometrial lesions. In addition, HEC1B, KLE, and HeLa cell lines were used to characterize EN2 overexpression in endometrial cancer cells. Immunohistochemistry, RT-PCR, and confocal analysis were used to detect the expression of EN2 protein in different cell lines.

In different groups, the average concentration of EN2 protein in cervical mucus in the EC group was significantly higher than that in the benign group and the normal control group (573.9 ± 123.4 ng/mL vs 153.5 ± 106.2 ng/mL and 153.0 ± 107.5 ng/mL, P < 0.001). The concentration of EN2 protein in EIN3 case specimens was significantly higher than that in the normal control group (P < 0.001). ROC analysis showed that the optimal threshold for diagnosing endometrial cancer in cervical mucus was 321.1 ng/ml, with a sensitivity of 92.6% and specificity of 95.4% for distinguishing EINIII, EC, and non-cancerous cases. In clinical specimens, the expression level of EN2 protein in endometrial cancer tissues was significantly higher than that in endometrial tissues and cervical tissues without endometrial cancer infiltration. In addition, PT-PCR, immunohistochemistry, suggest that EN2 protein is overexpressed in endometrial cancer cell lines compared to cervical adenocarcinoma cells (P < 0.01).

The concentration of EN2 protein in cervical mucus can effectively identify endometrial cancer and precancerous lesions. The increased expression of EN2 protein in endometrial cancer lesions leads to an increase in the concentration of EN2 protein in the cervical mucus of endometrial cancer patients.This is a small single-center study, and larger studies are needed to determine the role of EN2 protein in the diagnosis of endometrial cancer.

Betulinic acid, a compound classified as a pentacyclic triterpenoid, is found in abundance in a variety of medicinal plants and natural substances. Its broad spectrum of biological and medicinal properties, particularly its potent antitumor activity, has gained significant attention in recent years. The anticancer properties of betulinic acid are governed by mitochondrial signalling pathways and it exhibit selectivity for cancerous tissue, leaving non-cancerous cells and normal tissue unharmed. This characteristic is particularly valuable in chemo-resistant cases. Nevertheless, the medicinal potential of betulinic acid is hindered by its poor water solubility and short half-life, leading to sub-optimal effectiveness. This issue is being tackled by a variety of nano-sized drug delivery systems, such as polymeric nanoparticles, magnetic nanoparticles, polymeric conjugates, nanoemulsions, liposomes, nanosuspensions, carbon nanotubes, and cyclodextrin complexes. This article focuses on recent advances in nanoformulations that are tailored to the delivery of betulinic acid with enhanced effectiveness.

To establish and validate a 2-dimensional ultrasound (US) radiomics model for the noninvasive preoperative differentiation of various molecular subtypes of infiltrating breast cancer (IBC).

A retrospective analysis of 210 female patients diagnosed with IBC through surgical operation or needle biopsy pathology at our hospital between May 2019 and February 2024 was conducted. Relevant data were collected to establish predictive models for different molecular subtypes of IBC.

Based on 5936 US radiomics features, 39, 25 and 19 optimal features were identified for the differentiation of luminal versus nonluminal types, luminal A versus luminal B types and human epidermal growth factor receptor 2 (HER2) overexpression versus triple-negative (TN) IBC subgroups, respectively. The corresponding areas under the curve for the training and validation sets were 0.901 and 0.752 (luminal vs. nonluminal), 0.931 and 0.773 (luminal A vs. luminal B) and 0.962 and 0.842 (HER2 overexpression vs. TN), respectively, indicating robust discriminatory performance of these models for different pathological molecular subtypes of IBC.

A radiomics model based on US images is capable of effectively differentiating between various molecular subtypes of IBC prior to surgery, holding promise in assisting medical professionals in crafting tailored diagnostic and therapeutic strategies.

Prostate cancer (PCa) remains a significant public health challenge in the United States, disproportionately affecting African American (AA) men, who face higher incidence rates, more aggressive disease, and elevated mortality compared to Caucasian American (CA) men. This review explores the multifactorial underpinnings of these disparities, integrating genomic, socioeconomic, environmental, and systemic contributors. Genomic analyses reveal that AA men harbor distinct molecular alterations, including higher frequencies of FOXA1, BRAF, and CHD1 mutations, as well as DNA damage repair defects, highlighting the critical need for population-specific precision medicine. Immune-oncologic pathways and stromal interactions within the tumor microenvironment further underscore biological differences driving aggressive disease phenotypes. Concurrently, adverse social determinants-including limited access to care, lower PSA screening rates, delayed treatment, medical mistrust, and underrepresentation in clinical trials-contribute to poorer outcomes. Despite these challenges, evidence from equal-access healthcare systems indicates that when provided equitable treatment, AA men can achieve outcomes comparable to or better than their CA counterparts. This review emphasizes actionable strategies to reduce disparities, including increasing AA representation in clinical trials, enhancing culturally competent patient-provider communication, improving access to early detection and high-quality care, and expanding community-based outreach initiatives. A holistic, interdisciplinary approach is essential to dismantle systemic barriers and achieve health equity in prostate cancer outcomes.

Pancreatic ductal adenocarcinoma (PDAC) comprises a group of highly malignant tumors of the pancreas. Metabolic reprogramming in tumors plays a pivotal role in promoting cancer progression. However, little is known about the metabolic alterations in tumors that drive cancer drug resistance in patients with PDAC. Here, we identified acyl-CoA thioesterase 8 (ACOT8) as a key player in driving PDAC gemcitabine (GEM) resistance. The expression of ACOT8 is significantly upregulated in GEM-resistant PDAC tissues and is closely associated with poor survival in patients with PDAC. Gain- and loss-of-function studies have shown that ACOT8 drives PDAC GEM resistance both in vitro and in vivo. Mechanistically, ACOT8 regulates cellular cholesterol ester (CE) levels, decreases the levels of phosphatidylethanolamines (PEs) that bind to polyunsaturated fatty acids and promote peroxisome activation. The knockdown of ACOT8 promotes ferroptosis and increases the chemosensitivity of tumors to GEM by inducing ferroptosis-associated pathway activation in PDAC cell lines. The combination of orlistat, an ACOT8 inhibitor, and GEM significantly inhibited tumor growth in PDAC organoid and mouse models. This study reveals the biological importance of ACOT8 and provides a potential combination therapy for treating patients with advanced GEM-resistant PDAC.