Renal squamous cell carcinoma (RSCC) is an uncommon malignancy, representing less than 1% of all renal cancers, and is associated with a notably poor prognosis. Surgical intervention is the primary treatment modality for early and intermediate-stage cases; however, the efficacy of combined chemoradiotherapy and immunotherapy in advanced-stage patients remains unclear. In this report, we present a case of RSCC with pulmonary metastases, wherein the patient attained disease remission following a treatment regimen comprising combined chemo-radiotherapy and immunotherapy. The patient demonstrated a progression-free survival (PFS) of 12 months and an overall survival (OS) of 14 months. This case study aims to provide a comprehensive analysis of the treatment approach, potentially serving as a reference for therapeutic strategies in patients with inoperable RSCC.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a tumor microenvironment (TME) composed of a dense extracellular matrix, cancer-associated fibroblasts (CAFs), vasculature, neural elements, and immune cell populations. This complex network promotes tumor proliferation, invasion, metastasis, and resistance to immunotherapy and chemotherapy. The microenvironmental characteristics of the various PDAC subtypes are discussed in this review. And we examines the role of cancer cells in the TME, highlighting their ability to manipulate stromal components to serve as collaborators in tumor progression. Furthermore, we explored the formation mechanism of the immunosuppressive microenvironment in PDAC, paying attention on Inflammation and intrinsic genetic alterations, the regulatory effect of metabolic reprogramming, the contribution of CAFs and the role of immune cells in cancer cell metastasis. This review shows the role of soluble molecules and exosomes in facilitating PDAC progression and immune evasion within the microenvironment. In conclusion, we outline the novel therapeutic strategies that focus on the interaction between cancer cells and their microenvironment, with the objective of offering new insights for future precision medical interventions.

Tertiary Lymphoid Structures (TLSs) are ectopic lymphoid aggregates that form within the tumor microenvironment (TME) and are increasingly recognized as potential prognostic biomarkers in various cancers. However, the spatial heterogeneity and prognostic value of TLSs in esophageal squamous cell carcinoma (ESCC) remain poorly defined. This study aimed to characterize the spatial distribution patterns of TLSs and tumor-infiltrating lymphocytes (TILs), and to establish a refined prognostic model for ESCC patients in both surgery-only and neoadjuvant therapy cohorts.

Emerging evidence highlights the tumor microenvironment's (TME) crucial role in driving tumorigenesis and malignant progression. Disulfidptosis has recently been discovered as a non-apoptotic cell death mechanism triggered by intracellular disulfide stress. However, the impact of disulfidptosis within the dynamic modulation of the immune and stromal components in the TME of lung adenocarcinoma (LUAD) remains poorly characterized. In the presented study, RNA-seq and clinical data of LUAD patients were downloaded from TCGA; screening for genes associated with disulfidptosis and immune infiltration, revealed that fibrinogen alpha chain (FGA) modulates immune infiltration via disulfidptosis regulation. We also in-vitro experiments identified FGA suppression abrogates disulfidptosis through SLC7A11/xCT downregulation and attenuated disulfidptosis while concurrently enhancing malignant phenotypes, including cellular proliferation, migratory capacity, and invasive potential in LUAD models. This study reveals that FGA functions as a tumor suppressor that can impede the tumorigenesis of LUAD by modulating xCT expression, suggesting a novel therapeutic strategy enabling modulation of disulfidptosis for LUAD management.

Nucleoporin 188 (NUP188) is a vital component of the nuclear pore complex that regulates cancer progression, but its role in diagnosis, prognosis, and immunoregulation in pan-cancer remains unclear.

Mycosis fungoides (MF) and Sezary syndrome (SS) are the most prevalent cutaneous T-cell lymphomas, classified separately in the 2022 WHO Classification due to their distinct features. Despite advances, the mechanisms underlying disease progression-from early patch and plaque lesions to advanced tumor stages-remain incompletely understood. Chemokines and their receptors play crucial roles in the migration and survival of malignant T cells, influencing tissue invasion, immune evasion, and dissemination. This review highlights the altered expression of chemokine receptors like CCR4, CCR7, CCR8, CCR10, CXCR3, and CXCR4 in MF/SS and their contribution to disease evolution. It also explores the transition from a Th1 to a Th2 immune profile, linked to tumor progression. The dual role of chemokines in physiology and pathology is examined, with emphasis on their therapeutic potential in CTCL.

Locally advanced rectal cancer (LARC) constitutes a particularly challenging subtype of rectal cancer. Although traditional neoadjuvant chemoradiotherapy (nCRT) has demonstrated efficacy in enhancing local disease control and promoting sphincter preservation, its impact on long-term survival outcomes remains suboptimal. In recent years, combinatorial approaches integrating immune checkpoint inhibitors (ICIs) with nCRT have garnered increasing research interest. Nevertheless, individuals with proficient mismatch repair (pMMR)/microsatellite stable (MSS) LARC exhibit a notable resistance to immunotherapeutic strategies. This review thoroughly assesses the molecular features and treatment challenges linked to pMMR/MSS LARC, elucidates the functional pathways of ICIs, and explores their prospective synergistic effects when administered alongside nCRT. Moreover, recent progress in clinical investigations is summarized, and the utility of emerging biomarkers in facilitating patient selection and assessing treatment efficacy is critically appraised.

Aberrant pre-mRNA splicing is increasingly recognized as a key contributor to tumorigenesis and immune evasion. However, the regulatory factors orchestrating splicing dynamics within the tumor microenvironment (TME) remain incompletely understood. Here, we identify GPATCH3, a previously uncharacterized G-patch domain-containing protein, as a critical modulator of alternative splicing and immune regulation in cancer.

The objective of this study is to evaluate the incidence, prognostic value, and risk factors of progression of disease within 12 months (POD12) in patients with diffuse large B-cell lymphoma (DLBCL).

Gastric cancer, one of the leading causes of cancer-related mortality globally, faces challenges in treatment due to limitations in surgery, chemotherapy resistance, and high recurrence rates. Ferroptosis, an iron-dependent form of cell death, induces cell membrane rupture through dysregulated iron metabolism, lipid peroxidation, and the accumulation of reactive oxygen species (ROS), offering a promising therapeutic avenue for gastric cancer treatment. This article systematically explores the core mechanisms of ferroptosis, including iron overload catalyzing lipid peroxidation via the Fenton reaction, dysregulation of antioxidant systems (such as GPX4 and FSP1), and their associations with gastric cancer cell proliferation, metastasis, and resistance. Studies indicate that abnormalities in iron metabolism in gastric cancer cells, such as upregulation of TFR1 and dysregulated ferritin storage, significantly promote ferroptosis sensitivity, while ferroptosis inducers (such as Erastin and RSL3) can enhance chemotherapy sensitivity and reverse resistance by inhibiting GPX4 or system Xc-. Preclinical experiments confirm that targeting ferroptosis-related pathways (such as the USP7/SCD axis and ABCC2-mediated glutathione efflux) effectively inhibits tumor growth and metastasis. However, the dual-edged effect of ferroptosis warrants caution regarding its oxidative damage risk to normal tissues and potential pro-metastatic mechanisms. This article further proposes the potential of ferroptosis biomarkers (such as 4-HNE and GPX4) in early diagnosis and prognosis assessment of gastric cancer and emphasizes the need for precision medicine to optimize ferroptosis-targeted strategies, balancing efficacy and safety. Ferroptosis opens a new avenue for gastric cancer treatment, but its clinical translation still requires in-depth mechanistic exploration and personalized treatment plan design.

This case presents an 8-year-old girl diagnosed with B-cell acute lymphoblastic leukemia (B-ALL), who relapsed after 3 years of treatment and 1 year of complete remission, with an unusual extramedullary relapse in the ovary. Ovarian relapse of B-ALL is extremely rare in children, making this case noteworthy in scientific literature. The patient had an initial diagnosis of B-ALL with a deletion of chromosome 12, a genetic alteration previously associated with the ETV6-RUNX1 fusion gene, which is typically linked to a favorable prognosis but also carries a 20% risk of late relapse. The relapse was initially asymptomatic and went undetected until clinical symptoms of pelvic pain appeared. Imaging with pelvic ultrasound confirmed the ovarian involvement. The relapse was treated with standard chemotherapy protocols for B-ALL, resulting in a partial response. This case underscores the importance of considering extramedullary relapse in the differential diagnosis for pediatric ALL patients who present with atypical symptoms after remission. It also suggests that routine pelvic ultrasound could be a useful tool for early detection of ovarian and other extramedullary relapses, which are often associated with bone marrow relapse. The main take-away from this case is the necessity for vigilant follow-up, including targeted imaging, in ALL patient's post-remission to ensure early identification of extramedullary relapses, which can otherwise be easily overlooked. The presence of chromosome 12 deletion and its association with late relapse highlights the need for ongoing surveillance even in patients with initial favorable genetic abnormalities.

Background: Prostate cancer (PCa) poses a significant health burden for men, with docetaxel constituting the primary therapeutic option for patients with metastatic PCa. However, the mechanisms governing docetaxel resistance remain incompletely understood. Several studies have implicated the role of the extracellular matrix (ECM) stiffness in cancer drug resistance, yet the precise role of ECM stiffness in docetaxel resistance in PCa remains elusive. The aim of this study was to explore the influence of ECM stiffness on docetaxel resistance in PCa and elucidate the underlying molecular mechanisms, thereby providing novel insights into PCa treatment. Methods: Polyacrylamide gels of varying stiffness were utilized to mimic different ECM stiffness conditions. The sensitivity of PCa cells to docetaxel was evaluated using CCK-8, TUNEL staining, flow cytometry, and western blotting. RNA-seq was employed to analyze the transcriptomic effects of different ECM stiffness on PC-3 cells. Western blotting, qPCR, and siRNA were utilized to validate the regulatory role of the key gene in the sensitivity of PCa cells to docetaxel under varying stiffness conditions. Results: Our findings indicate that high ECM stiffness enhances docetaxel resistance in PCa cells by inhibiting docetaxel-induced apoptosis. This process is mediated through the integrin-related mechanotransduction pathway. Specifically, high ECM stiffness upregulates the expression of PRRX1, thereby promoting docetaxel resistance in PCa cells. Conclusions: High ECM stiffness promotes docetaxel resistance in PCa, with PRRX1 identified as a pivotal gene in this process. These findings contribute to a deeper understanding of the mechanisms underlying docetaxel resistance in PCa and may inform the development of novel therapeutic strategies.

To investigate the practicability of a radiomics signature combined with clinical factors and molecular biomarkers for predicting overall survival (OS) in glioma patients.

Inflammation, immune system and nutritional status contribute significantly to tumorigenesis, progression and metastasis. The aim of this study was to evaluate the significance of the inflammation-immune-nutritional score (IINS) on postoperative survival and recurrence in breast cancer patients and to analyze and compare the IINS, platelet-to-lymphocyte ratio (PLR), and the prognostic nutritional index (PNI) in terms of progression-free survival (PFS) and overall survival (OS) in patients with breast cancer (BC) who underwent surgical treatment prognostic value.

The prognosis of patients with hepatocellular carcinoma (HCC) remains suboptimal due to limited biomarkers. Although ferroptosis and cuproptosis have emerged as promising therapeutic targets, their prognostic significance in HCC remains unclear.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality worldwide, with poor prognosis and limited treatment options for advanced stages. Dysregulation of cadherin expression has been implicated in various cancers, but their exact roles and diagnostic potential of these genes in NSCLC remain unclear. The aim of this study is to investigate the diagnostic and prognostic significance of cadherin family genes (CDH1, CDH2, and CDH3) in NSCLC. This study follows an experimental design, involving both in vitro analyses of cell lines and survival data analysis from public databases. Nine NSCLC cell lines and five normal lung tissue-derived cell lines were cultured and CDH1, CDH2, and CDH3 expression was analyzed via RT-qPCR. Protein expression was validated using the Human Protein Atlas and survival analysis was conducted with the Kaplan-Meier database. Functional roles and regulatory mechanisms of cadherin genes were explored through mutational analysis, PPI networks, and miRNA interactions. The results revealed that all three cadherin genes were significantly upregulated in NSCLC cell lines and tissue samples compared to normal controls. Mutational and copy number variation analyses revealed frequent alterations in CDH2, CDH3, and CDH1 in NSCLC. Additionally, we identified hsa-miR-217, hsa-miR-203a-3p.2, and hsa-miR-6766-3p as potential regulatory miRNAs. The results of functional assays indicate that the silencing of CDH1 and CDH2 inhibits cell proliferation, colony formation, and migration in A549 cells, highlighting their potential roles in promoting tumorigenic and migratory properties in NSCLC. Collectively, our findings suggest that cadherin family genes (CDH1, CDH2, and CDH3) play critical roles in NSCLC tumorigenesis and progression, highlighting their significance as diagnostic markers.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, necessitating accurate and robust predictive approaches to assist oncologists with prognosis prediction and therapeutic decision-making in clinical practice. Here, we aimed to identify key genes involved in colorectal cancer pathology and develop a model for prognosis prediction and guide therapeutic decisions in CRC patients. We profiled 49 matched tumour and normal formalin-fixed paraffin-embedded (FFPE) samples using Affymetrix HGU133-X3P arrays and identified 845 differentially expressed genes (FDR ≤ 0.001, fold change ≥2), predominantly enriched in the extracellular matrix (ECM)-receptor interaction pathway. The integrative analysis of our data with publicly available mRNA and miRNA datasets, including their differentially expressed gene analyses, identified four overexpressed genes in the ECM-receptor interaction pathway as key regulators of human CRC development and progression. These four genes were independently validated for their differential expression and association with prognosis in a newly collected CRC cohort and publicly available datasets. A prognostic risk score was developed using these genes, with patient stages weighted by multivariate Cox regression coefficients to stratify patients into low-risk and high-risk groups, showing significantly poorer overall survival (OS) in the high-risk group. In conclusion, our risk assessment model exhibits strong potential for predicting poor survival and unfavorable clinicopathological features in CRC patients, offering valuable insights for personalised management strategies.

Background: The high morbidity and mortality of lung adenocarcinoma (LUAD) are partly caused by a lack of sensitive and reliable molecular markers for early diagnosis. Programmed cell death (PCD) is a crucial process involved in tumorigenesis and immune regulation, and identifying PCD-correlated genes may contribute to the precision diagnosis and targeted therapy of LUAD. Methods: LUAD samples were acquired from UCSC Xena and Gene Expression Omnibus (GEO) database. PCD-correlated module genes were identified by WGCNA. "Limma" package was employed for screening differentially expressed genes (DEGs) between LUAD and control samples, followed by conducting functional enrichment analysis with "ClusterProfiler" package. Hub genes were selected through machine learning algorithms. Biomarkers for LUAD were screened and further validated by receiver operating characteristic (ROC) analysis. The robustness of the diagnostic model was verified by the confusion matrix. Immune cell infiltration was assessed employing "ESTIMATE" and "GSVA" packages. HALLMARK pathway score was calculated with the "GSVA" package. Transcription factor (TF)-biomarker-chemical network was established using NetworkAnalyst and Cytoscape software. The expressions of the biomarkers in LUAD cells were detected by in vitro experiments. The viability, migration, and invasion of the LUAD cells were measured by CCK-8, wound healing, and Transwell assays. Results: We identified 160 module genes and 5934 DEGs. Then, eight hub genes were selected applying LASSO and support vector machine-recursive feature elimination (SVM-RFE) analyses. Further, FGR, TLR4, and NLRC4, which showed an area under the ROC curve (AUC) > 0.7, were determined as the diagnostic biomarkers for LUAD. Interestingly, they were all low expressed in LUAD samples. We developed a diagnostic model that demonstrated robust performance in distinguishing LUAD samples from normal controls. The three biomarkers showed positive correlation to the infiltration of most immune cells and enrichment in HALLMARK pathways associated with inflammation, immune regulation, and cytokine signaling. Moreover, nine TFs and nine small-molecule compounds targeting the three biomarkers were predicted to construct a TF-biomarker-chemical network. Functional validation revealed that all the three biomarkers were significantly downregulated in LUAD cells. Notably, FGR overexpression markedly suppressed LUAD cell proliferation, migration, and invasion. Conclusion: This study identified three PCD-related biomarkers for LUAD diagnosis, providing new potential therapeutic targets.

Background: Neuroblastoma (NB) differentiation status critically influences prognosis and treatment response. Although differentiation therapy has shown clinical benefit, its efficacy remains limited. The molecular mechanisms driving NB differentiation are not fully understood. PLK4 has been linked to NB tumorigenesis, but its role in regulating differentiation remains unclear. Methods: We investigated the role of PLK4 in neuroblastoma differentiation by modulating its expression both in vitro and in vivo. Through comprehensive analyses employing Western blotting, co-immunoprecipitation, immunofluorescence and murine neuroblastoma models, we identified downstream signaling pathways involved in PLK4-mediated regulation of neuronal genes. Pharmacological inhibition of PLK4 further confirmed its functional relevance in promoting neuroblastoma differentiation. Results: PLK4 functions as a key regulator of neuroblastoma differentiation. Its depletion enhances neuronal maturation and sensitizes cells to 13-cis RA. Mechanistically, we identify a novel PLK4-CXCR4 signaling axis that governs neuroblastoma differentiation through PI3K/Akt-mediated modulation of cyclin D1 expression. The selective PLK4 inhibitor CFI-400945 exhibits dual anti-tumor activity by promoting terminal differentiation and suppressing proliferation. Conclusions: Our study identifies PLK4 as a potential molecular switch governing NB differentiation and a promising therapeutic target to overcome resistance to 13-cis RA.

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Long noncoding RNAs (lncRNAs) have emerged as crucial regulators in the initiation and progression of various malignancies, including CRC. In this study, we found that lnc-CRAT40 was upregulated in CRC and associated with poor prognosis following CRC resection. Functional assays revealed that elevated lnc-CRAT40 expression promotes tumor cell proliferation and metastasis both in vitro and in vivo. The modification of N6-methyladenosine, driven by METTL3, was essential for the stability of lnc-CRAT40, which may partially contribute to the upregulation of lnc-CRAT40. Mechanistically, lnc-CRAT40 directly interacted with Y-box binding protein 1 (YBX1) and recruits it to the RelA promoter, thereby activating NF-κB signaling, which in turn drives CRC proliferation and metastatic potential. These findings provide novel insights into the molecular mechanisms underlying CRC progression and highlight lnc-CRAT40 as a potential prognostic biomarker and therapeutic target.