Recent research has identified pyroptosis as a distinct form of programmed cell death that is strongly correlated with tumor outcomes. However, its value as a prognostic biomarker in clear cell renal cell carcinoma (ccRCC) is not yet fully established.

Differential expression of pyroptosis-related genes between ccRCC and normal tissues was identified using the DESeq2 R package. Next, univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses using data from The Cancer Genome Atlas cohort were applied to develop a prognostic model. Univariate and multivariate prognostic analyses were conducted to determine whether the risk score could independently predicted patient prognosis after adjustment for clinicopathological characteristics. A nomogram was then constructed to estimate patient survival probability, supporting clinical decision-making. Expression of pyroptosis-related proteins was assessed using tissue proteomic data from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. Additionally, the Tumor-Immune System Interaction Database (TISIDB) database was used to analyze immune cell infiltration, whereas gasdermin B (GSDMB) expression in ccRCC cell lines was assessed by Western blot (WB) and quantitative PCR (qPCR) experiments, with immunohistochemistry applied to measure the levels of GSDMB and programmed cell death protein 1 (PD-1).

A prognostic risk model was developed using nine genes related to pyroptosis (AIM2, CASP5, GSDMB, GSDMD, NLRP7, NOD2, PYCARD, SCAF11, and NLRP6), employing both univariate Cox and LASSO regression analyses. Based on the median risk score, ccRCC samples were divided into high- and low-risk categories, with Kaplan-Meier analysis revealing poorer survival rates for the high-risk group. Time-dependent receiver operating characteristic curve analysis confirmed the predictive performance of the model for ccRCC prognosis. Furthermore, a nomogram with calibration plots was developed to predict 1-, 3-, and 5-year survival probabilities for patients with ccRCC. Notably, these pyroptosis-related genes were strongly correlated with immune cell infiltration, including cytotoxic cells, CD56bright natural killer cells, and T helper cells. Subsequently, qPCR and WB analyses confirmed elevated GSDMB expression in ccRCC cells, and immunohistochemistry demonstrated a strong correlation between GSDMB and PD-1 expression.

Pyroptosis-associated genes, namely AIM2, CASP5, GSDMB, GSDMD, NLRP7, NOD2, PYCARD, SCAF11, and NLRP6, are promising prognostic biomarkers for ccRCC, and may serve as prognostic biomarkers for predicting patient survival and informing immunotherapy strategies.

Accurate identification of actionable somatic variants is essential for therapeutic stratification in colorectal cancer (CRC). While next-generation sequencing (NGS) enables comprehensive genomic profiling, targeted approaches may provide faster and more practical alternatives for routine diagnostics.

This study evaluated the analytical performance of the Agena Bioscience iPLEX® High Sensitivity (HS) Colon Panel using MassARRAY MALDI-TOF technology for detection of hotspot variants in KRAS, NRAS, BRAF, and PIK3CA from formalin-fixed paraffin-embedded (FFPE) specimens. A total of 60 unique clinical and reference samples were analyzed, targeting 26 single-nucleotide variants and compared with an orthogonal targeted NGS assay. Limit of detection (LOD) was assessed using serial dilutions of reference materials, and intra- and inter-run reproducibility was evaluated across multiple runs. Analytical performance metrics including positive and negative percent agreement, predictive values, and error rates were calculated.

The assay demonstrated complete concordance with NGS across all evaluated variants, requiring only 20 ng of DNA input, compared to 80-120 ng for a successful NGS run. LOD studies showed reliable detection of multiple variants at approximately 5% variant allele frequency, with BRAF p.V600E detectable near 1%. Intra- and inter-run analyses achieved 100% concordance, confirming assay reproducibility. Aggregated performance metrics demonstrated high sensitivity and specificity across a heterogeneous sample set.

These findings establish the iPLEX® HS Colon Panel as a reliable platform for rapid detection of clinically actionable hotspot mutations. This study represents analytical validation using mixed FFPE tumor specimens; evaluation in larger colorectal cancer cohort, is warranted.

Patients with solid tumors receiving systemic anticancer therapy face an increased risk of herpes zoster (HZ), a complication that can delay or disrupt ongoing oncologic treatments. Although the recombinant zoster vaccine (RZV) is recommended for immunocompromised adults, real-world data on its implementation and tolerability during active cancer treatment settings remain limited. We conducted a retrospective, single-center observational study at the Oncology Department of the "G. Martino" University Hospital, Messina, Italy. Between July 2022 and January 2025, the standard two-dose RZV schedule was systematically offered to adult patients with solid tumors who were receiving or scheduled to start systemic therapies. Endpoints included the operational feasibility of vaccination during oncologic care, safety, and HZ occurrence during follow-up. Overall, 42 patients received at least one RZV dose, and 37 (88.1%) completed the two-dose schedule. Patients were receiving different systemic anticancer treatments, mainly chemotherapy (59.5%), followed by chemo-immunotherapy and immunotherapy. RZV showed a favorable safety profile. Injection-site pain was the most frequently reported local adverse event, while systemic reactions, including fever and headache, were mild and transient. No severe vaccine-related adverse events or delays in oncologic treatment were observed. After a median follow-up of 11.5 months, no clinically documented HZ episodes occurred, although this finding should be interpreted descriptively given the limited sample size. Our experience suggests that integrating RZV into routine outpatient oncology workflows is feasible and well tolerated in patients undergoing active systemic treatments.

To assess the protective effects of live combined bifidobacterium, lactobacillus, enterococcus, and glutamine on diarrhea associated with chemotherapy and inflammatory markers in colorectal cancer patients (CCP). A retrospective analysis was conducted on the clinical data of patients with colorectal cancer who received chemotherapy at the People's Hospital of Pailin County, Chongqing from December 2022 to December 2024. There were 59 cases in the control group and 59 cases in the study group. The control group received treatment with triple live bifidobacterium, while the study group received combined treatment with glutamine in addition to the treatment of the control group. We compared levels of inflammatory markers, intestinal barrier functions, immune responses, and diarrhea incidence during chemotherapy. No significant pre-chemotherapy differences were noted in inflammatory or intestinal barrier markers (P > 0.05). Throughout the course of treatment, we observed a reduction in inflammatory markers in both groups (P < 0.05), with the experimental group showing more significant declines. Intestinal barrier functions degraded over time in both groups, with more significant reductions in the study group (P < 0.05). The therapy combining significantly mitigates inflammation, bolsters intestinal and immune functions, and alleviates diarrhea in CCP. Clinical Registration: The authors have nothing to report.

To elucidate the diagnostic value and clinical relevance of protein kinase D3 (PRKD3) in hepatocellular carcinoma (HCC), we analyzed data retrieved from The Cancer Genome Atlas (TCGA) database, which revealed high expression of PRKD3 in HCC tissues. Subsequently, we collected a total of 392 clinical plasma samples from healthy individuals, patients with cirrhosis or decompensated cirrhosis, and patients with HCC. Plasma PRKD3 levels were then determined across HCC patients and individuals at high risk of developing the disease. The results revealed significantly elevated PRKD3 concentrations in patients with cirrhosis, decompensated cirrhosis, and HCC compared to healthy controls (P<0.01). The areas under the receiver operating characteristic (ROC) curve for these three groups were 0.8107, 0.7899, and 0.7177, respectively. To further evaluate the efficacy of PRKD3 as an adjunctive diagnostic biomarker for HCC, we employed a panel of machine learning algorithms as primary classifiers, including extra trees (ET), gradient boosting (GB), random forest (RF), and support vector machine (SVM). A multi-parameter joint diagnostic model was constructed by combining PRKD3 expression data with a set of clinical parameters, including gender, age, total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin (ALB), alpha-fetoprotein (AFP), and prothrombin induced by vitamin K absence-II (PIVKA-II). This integrated approach exhibited substantially improved diagnostic performance, achieving an accuracy of 0.861, sensitivity of 0.863, specificity of 0.925, and precision of 0.862. Collectively, these findings highlight the potential of PRKD3 as an integral component of a comprehensive diagnostic tool for the early identification of HCC.

Programmable RNA-cleaving DNAzymes (RCDs) represent a unique class of catalytic nucleic acids that couple molecular recognition with enzyme-like activity. While DNAzymes have traditionally been explored for targeted gene regulation, recent advances in nanotechnology have repositioned them as programmable biosensing modules with stimuli-responsive therapeutic potential. When integrated into metal-oxide scaffolds, DNA-framework architectures, or metal-organic frameworks, DNAzymes form hybrid platforms that create confined catalytic microenvironments, provide enriched cofactor availability, and facilitate microenvironment-responsive activation. These engineered systems can function as nanoscale biosensing modules that respond to pH, redox gradients, metal ions, or microRNA signatures and convert these biological cues into catalytic outputs. Beyond enhancing analytical performance, such platforms may also reshape tumor immunometabolism. Through the selective cleavage of metabolic or immune-regulatory transcripts, DNAzyme nanocatalysts can directly reprogram glycolysis, redox balance, oxygen tension, and mitochondrial activity, and these metabolic changes in turn alleviate immunosuppression and promote innate and adaptive immune activation. This review outlines the mechanistic foundations of DNAzyme catalysis, summarizes recent nanoengineering strategies that endow DNAzymes with programmable sensing and stimuli-responsive functions, and discusses how these systems bridge biosensing and catalytic immunometabolic functions. We conclude with perspectives on translational challenges and opportunities, endorsing programmable DNAzyme nanocatalysts as emerging preclinical platforms for biosensing-guided immunometabolic intervention.

The chemotherapy resistance genes in breast cancer are closely related to prognosis. This study is aimed at exploring the key genes that may be involved in chemotherapy resistance of breast cancer and establishing a prognostic model.

Using data from the GEO database, differentially expressed genes (DEGs) related to chemotherapy resistance in breast cancer were identified. Univariate and multivariate Cox regression were used to identify the association between DEGs and prognosis. Subsequently, functional analysis was conducted to characterize the functions of DEGs. In addition, immune-related analysis was performed to study the functions of these hub genes. LASSO-Cox regression analysis narrowed the range of hub genes. A DRFS prognostic nomogram model was constructed using the hub genes. A total of 60 breast cancer patients from the Second Affiliated Hospital of Fujian Medical University were selected as the external validation set.

By comparing the gene expression profiles of the Rx_Insensitive group and the Rx_Sensitive group, 162 DEGs were screened out, among which 53 DEGs were upregulated and 109 DEGs were downregulated. Univariate Cox regression analysis of the 162 DEGs with survival showed that GREB1, DACH1, STAP1, TDRD12, and SCGB1D2 were significantly associated with prognosis (all p < 0.05). Further multivariate Cox regression analysis revealed that GREB1 (HR = 0.653), DACH1 (HR = 1.217), STAP1 (HR = 1.140), and SCGB1D2 (HR = 1.074) were independent risk factors for prognosis (all p < 0.05). Moreover, the expression levels of GREB1, DACH1, STAP1, and SCGB1D2 were significantly correlated with the infiltration levels of various immune cells (p < 0.05). Based on these five breast cancer chemotherapy resistance-related genes, a new prognostic model for breast cancer was constructed. The 1-year AUC of this model was 0.748, 3-year AUC was 0.735, and 5-year AUC was 0.679. In the validation set, the 1-year AUC was 0.744, 3-year AUC was 0.696, and 5-year AUC was 0.650. The calibration curve showed that the predicted probabilities of the model were close to the true values. The model's prediction accuracy on the external validation set for 1 year was 0.823.

The prognostic model developed based on the five breast cancer chemotherapy resistance-related genes (GREB1, DACH1, STAP1, TDRD12, and SCGB1D2) has good predictive performance for BRCA patients.

To report the management of an advanced cutaneous squamous cell carcinoma (SCC) with parotid gland invasion, emphasizing surgical treatment with facial nerve preservation and reconstruction using a supraclavicular fasciocutaneous flap. A 64-year-old man presented with a rapidly growing ulcerated lesion in the right malar region measuring approximately 5.0 cm × 4.0 cm. Imaging suggested parotid gland involvement without regional lymph node metastasis (cT3N0M0), which was subsequently confirmed histopathologically. The patient underwent wide local excision and parotidectomy extending to the deep lobe following identification of a positive deep margin on frozen-section analysis, while preserving the facial nerve. Reconstruction was performed using a supraclavicular fasciocutaneous flap. Histopathological examination confirmed a moderately differentiated SCC with parotid gland invasion and clear surgical margins. Adjuvant radiotherapy was subsequently administered. Advanced cutaneous SCC of the face requires multidisciplinary management. Radical surgical resection with intraoperative margin assessment may allow preservation of critical structures such as the facial nerve, while the supraclavicular fasciocutaneous flap remains a reliable reconstructive option for extensive cervicofacial defects.

This study aimed to evaluate the first-line treatment patterns and prognostic factors associated with survival in patients with driver gene-negative non-small cell lung cancer (NSCLC) and liver metastases, in order to identify the optimal treatment strategy.

A Bayesian network meta-analysis was performed using R software (version 4.2.3) and RevMan (version 5.4) to systematically compare the efficacy of various first-line treatment regimens, including chemotherapy, immunotherapy, and combination therapy, in patients with driver gene-negative NSCLC with liver metastases.

A total of 20 randomized controlled trials were included. Among patients with driver gene-negative NSCLC and liver metastases: (1) PD-1 inhibitor plus chemotherapy significantly improved progression-free survival (PFS) (HR = 0.572, 95% CI: 0.435-0.754) and overall survival (OS) (HR = 0.681, 95% CI: 0.559-0.830) compared with chemotherapy alone. (2) In the patients with non-squamous NSCLC, PD-1/PD-L1 inhibitor plus chemotherapy resulted in a greater PFS benefit than chemotherapy alone. (3) A similar PFS advantage was observed in patients with squamous NSCLC receiving PD-1 inhibitor plus chemotherapy versus chemotherapy alone (HR = 0.583, 95% CI: 0.386-0.882). (4) Camrelizumab plus chemotherapy (CAM+CT) ranked highest in the network meta-analysis, with the top SUCRA values for both PFS (84.18%) and OS (96.38%).

In treatment-naive driver gene-negative NSCLC with liver metastases: PD-1 inhibitor plus chemotherapy conferred more significant PFS and OS benefits than chemotherapy alone. CAM+CT appeared to rank favorably among the evaluated regimens, particularly in patients with squamous NSCLC and liver metastases, suggesting it may represent a candidate treatment strategy. However, given that these findings were derived from a network meta-analysis based on indirect comparisons, they should be interpreted with caution.

https://www.crd.york.ac.uk/PROSPERO/view/CRD42025632364, identifier CRD42025632364.

Since the introduction of the hallmarks of cancer framework over 25 years ago, treatment approaches have evolved into personalized medicine, offering benefits to select patient populations. However, three major components of heterotypic interactions in cancer-mutational evolution of cancer stem cells, epithelial-mesenchymal plasticity (EMP), and cancer-remodeled extracellular matrix (ECM)-remain critical barriers to therapy, particularly in patients who have failed treatment. EMP encompasses a spectrum of to-and-fro transitions between mesenchymal and epithelial states, yielding hybrid phenotypes of evolutionary heterogeneity. These are embedded in the vascular, metabolic, mutational, and immune-suppressive reprogramming of the tumor microenvironment (TME), induced and advanced by the hypoxia-reactive oxygen species (ROS)-hypoxia-inducible factor-1α (HIF-1α)-transforming growth factor-β (TGF-β) signaling axis. This review systematically examines the molecular mechanisms underlying EMP, tumor heterogeneity, and the hallmarks of cancer. It explores pharmacological strategies to target tumor burden, epigenetically revert transitional states, and restore immune-editing functions. Based on this analysis, we propose a phased anti-hallmark Combinations, Timing, and Sequencing (CTS) protocol. The methodology integrates vascular normalization, epigenetic modifiers, trimodal radiotherapy or stereotactic body radiotherapy (SBRT), chemotherapy (CT), and immunotherapy optimization, aiming to improve outcomes while minimizing toxicities. Also, mechanistically, by reverting mesenchymal phenotypes and normalizing the vasculature, the CTS protocol is designed to rescue the immune-suppressive tumor microenvironment-curtailing the recruitment of myeloid-derived suppressor cells (MDSCs) and regulatory T (Treg) cells. This restores cytotoxic T-cell homing, thereby converting immunologically "cold" tumors into "hot," immunotherapy-responsive lesions.