Despite the relatively rare incidence of para-aortic lymph node metastasis (PALNM) after surgery for colorectal cancer, it is often fatal, and treatment strategy is still debated. This study aimed to investigate the long-term outcomes of patients with metachronous PALNM and their prognostic factors.

Arginine methyltransferase 1 (PRMT1) is widely recognized as an oncogene in various cancers. However, its specific role and underlying mechanisms in hepatocellular carcinoma (HCC) remain insufficiently understood. This study investigated the function of PRMT1 in HCC development and immune evasion. A comprehensive approach combining database analysis (including TCGA, The Human Protein Atlas, Kaplan-Meier Plotter, and TIMER2.0), molecular techniques (such as RT-qPCR, Western blot analysis, and co-immunoprecipitation), cell-based assays (including MTT, colony formation, transwell, and T cell killing assays), and in vivo models was employed to explore PRMT1's role in HCC. The findings revealed a marked upregulation of PRMT1 in both HCC clinical samples and cell lines. Depletion of PRMT1 inhibited cell proliferation and immune evasion while reducing cell migration and invasion. Mechanistically, PRMT1 was shown to interact with MYC, facilitating its arginine methylation and enhancing its protein stability. Moreover, re-expression of MYC significantly reversed the anti-tumour effects associated with PRMT1 depletion. In vivo experiments further corroborated these results. Collectively, PRMT1 promotes HCC progression and immune escape by mediating ADMA methylation of MYC, thereby regulating its stability and expression.

Bladder cancer (BCa) is a highly invasive tumor with few successful therapies, and its unfavorable prognosis mainly stems from late diagnosis and resistance to treatment. Ferroptosis is a type of non-apoptotic cell death characterized by iron-dependent regulated necrosis due to extensive lipid peroxidation. Glycolysis is fundamental to cancer cell metabolism, with cancer cells developing various strategies to enhance this process. In this study, we combined ferroptosis and glycolysis gene sets, two biological processes closely related to tumorigenesis and development, and obtained ferroptosis and glycolysis-related gene sets (FGRGs). By leveraging both single-cell and bulk transcriptome data from BCa, we have investigated the presence and role of FGRGs in the onset and progression of BCa through various approaches. Using machine learning algorithms, we identified a feature gene set consisting of 13 genes in the TCGA data set to predict the prognosis of BCa and verified it in the GEO data set. After that, we explored FGRGs in depth using a variety of bioinformatics analyses, such as mutational landscape analysis, functional enrichment analysis, immune infiltration analysis, FGRGs-associated risk and clinical characterization, and drug susceptibility analysis. Finally, we validated the function of the core gene chondroitin polymerizing factor 2 (CHPF2) using CCK-8, clone formation, transwell, and wound healing assays. Our research innovatively combines ferroptosis with glycolytic genes and applies it as an independent prognostic factor in the study of BCa. It reveals new characteristic genes and therapeutic targets that can predict the prognosis of BCa patients and lays a foundation for the study of the occurrence and development mechanism of BCa and targeted data strategies.

Emerging evidence suggests that dysregulated RNA-binding proteins (RBPs) are associated with a wide variety of cancers. However, the exact roles and pathways of RBPs in the tumorigenesis of hepatocellular carcinoma (HCC), the most common subtype of liver cancer, remain largely unknown. Here, we systematically searched for altered RBP candidates in HCC through multi-omics data integrative analyses and identified that GPATCH4 gene is amplified in >70% HCC patients and its high expression predicts poor prognosis. We mapped the in vivo RNA binding sites of GPATCH4 by iCLIP-seq and characterized that GPATCH4 primarily bound ribosomal RNA (rRNAs). GPATCH4 promoted HCC cell proliferation and transformation both in vitro and in vivo through increasing rRNA transcription and global protein synthesis. GPATCH4 is mainly localized in the nucleolus and helps to unwind RNA loops formed at the rDNA through interacting with DDX21 via its C-terminal intrinsically disordered region. Removal of accumulated R-loops induced by GPATCH4 depletion rescued decreased rRNA transcription and cell proliferation. Taken together, we characterized the understudied GPATCH4 as an RBP with oncogenic function in HCC and revealed a new mechanism by which GPATCH4 functions as a regulator of nucleolar R-loops to control rRNA transcription through interacting with DDX21.

Recent research highlighted the contribution of extracellular matrix, and particularly of ADAMTS proteases, in immune regulation. Now, our work with melanoma and mammary tumor models revealed that tumor blockade induced by the lack of Adamts1 led to an increased vascular deposition of its substrate, the basement membrane glycoprotein NIDOGEN-1 (NID1). Significantly, the overexpression of NID1 in the melanoma syngeneic model also blocked tumor progression, disclosing an overlapping phenotype with the absence of Adamts1. These tumors showed important alterations in their immune infiltrates, emphasizing an enhanced presence of antitumorigenic macrophages and a global inflammatory landscape. We corroborated in vitro that full length NID1, but not its fragments, promoted an M1-like macrophage polarization, mainly mediated by the αvβ3 integrin. Significantly, the projection of RNA-seq from our tumor models to two large human melanoma datasets allowed us to discover a new gene signature associated with good prognosis and the abundance of M1-like macrophages. These results support NID1 as a novel tumor suppressor with immunomodulatory properties, and unveil the existence of key oncological drivers in the extracellular scenario.

Stem cells play a pivotal role in the malignant behavior of gastric cancer (GC), complicating its treatment and prognosis. However, the regulatory mechanisms of GC stem cells (GCSCs) remain poorly understood. DAZ-associated protein 1 (DAZAP1), a splicing regulator linked to various malignancies, has an unclear role in GC. This study investigated DAZAP1's impact on GC stemness and its mechanisms. DAZAP1 promoted tumor progression in GCSCs, as shown by sphere formation assays and stemness marker analysis. Functional enrichment analysis suggested that DAZAP1 enhanced tumor stemness by promoting oxidative phosphorylation (OXPHOS), which was validated through Seahorse assays and measurements of mitochondrial potential. Transmission electron microscopy and immunofluorescence analyses demonstrated that DAZAP1 promoted mitophagy. RNA immunoprecipitation and PCR analysis revealed that DAZAP1 regulated the splicing and expression of the mitophagy-related gene ULK1 through nonsense-mediated mRNA decay. Rescue experiments showed that overexpression of ULK1 reversed the suppression of GC stemness and OXPHOS levels induced by DAZAP1 silencing. Our findings indicate that DAZAP1 reduces ULK1 decay, thereby activating mitophagy and enhancing OXPHOS to fulfill the metabolic demands of cancer stem cells. These findings highlight the therapeutic potential of DAZAP1 as a target for treating GC.

Although chronic inflammation is implicated in the pathogenesis of diffuse large B-cell lymphoma (DLBCL), the mechanisms responsible are unknown. We demonstrate that the overexpression of the collagen receptor, DDR1, correlates with reduced expression of spindle checkpoint genes, with three transcriptional signatures of aneuploidy and with a higher frequency of copy number alterations, pointing to a potential role for DDR1 in the acquisition of aneuploidy in DLBCL. In support of this, we found that collagen treatment of primary germinal centre B cells transduced with DDR1, not only partially recapitulated the aberrant transcriptional programme of DLBCL but also downregulated the expression of CENPE, a mitotic spindle that has a crucial role in preventing chromosome mis-segregation. CENPE expression was also downregulated following DDR1 activation in two B-cell lymphoma lines and was lost in most DDR1-expressing primary tumours. Crucially, the inhibition of CENPE and the overexpression of a constitutively activated DDR1 were able to induce aneuploidy in vitro. Our findings identify a novel mechanistic link between DDR1 signalling and chromosome instability in B cells and provide novel insights into factors driving aneuploidy in DLBCL.

27-Hydroxycholesterol (27HC), a cholesterol metabolite, functions both as a selective oestrogen receptor (ER) modulator and a ligand for liver X receptors (LXRs). The discovery of 27HC involvement in carcinogenesis has unveiled new research avenues, yet its precise role remains controversial and context-dependent. In this review, we provide an overview of the biosynthesis and metabolism of 27HC and explore its cancer-associated signalling, with a particular focus on ER- and LXR-mediated pathways. Given the tissue-specific dual role of 27HC, we discuss its differential impact across various cancer types. Furthermore, we sort out 27HC-contributed drug resistance mechanisms from the perspectives of drug efflux, cellular proliferation, apoptosis, epithelial-mesenchymal transition (EMT), antioxidant defence, epigenetic modification, and metabolic reprogramming. Finally, we highlight the chemical inhibitors to mitigate 27HC-driven cancer progression and drug resistance. This review offers an updated role of 27HC in cancer biology, setting the stage for future research and the development of targeted therapeutics.

IntroductionThoracic SMARCA4-deficient tumors, which are rare and aggressive malignancies found in the lung or thoracic cavity, present a challenge in treatment standardization. This challenge arises from their resistance to chemotherapy and the absence of targeted therapy options.MethodsThoracic SMARCA4-deficient tumors were identified retrospectively using pathology databases. The clinicopathological characteristics of these tumors are outlined, and the clinical outcomes of advanced patients treated with immune checkpoint inhibitors (ICIs) in combination with chemotherapy and chemotherapy alone are reviewed.ResultsThirty-nine patients had thoracic SMARCA4-deficient tumors, with a median age of 62 years. The cohort consisted of 92.3% males, and 89.7% had a history of smoking. Within this group, 94.9% had stage III/IV disease at diagnosis. SMARCA4-deficient non-small cell lung cancer (SMARCA4-DNSCLC) and SMARCA4-deficient undifferentiated tumors (SMARCA4-DUT) display distinct histological and immunohistochemical features. Thirty-five patients underwent systemic therapy, achieving an ORR of 51.4%, a DCR of 82.9%, and a median OS of 20.9 months. Patients were categorized into chemotherapy (28.6%) and ICIs plus chemotherapy (71.4%) groups. The ICIs plus chemotherapy group exhibited an ORR of 64.0% and a DCR of 96.0%, while the chemotherapy group had an ORR of 20.0% and 50.0%, respectively (P < .0001 for ORR and DCR). The median OS for ICIs plus chemotherapy and chemotherapy groups were 20.9 months and 6.5 months, and median PFS were 9.6 months and 3.5 months, respectively, all statistically significant (P < .05). Multivariate COX regression analysis indicated that treatment was an independent prognostic factor for OS.ConclusionThoracic SMARCA4-deficient tumors exhibit a lack of SMARCA4 expression, displaying high malignancy and aggressiveness while exhibiting poor response to standard chemotherapy. The combination of ICIs with chemotherapy could potentially serve as an effective treatment approach for thoracic SMARCA4-deficient tumors.

Non-melanoma skin cancers (NMSCs), including basal (BCC) and squamous cell carcinoma (SCC), are the most prevalent malignancies affecting the skin, with the head and neck region being the most common site of involvement. Surgical excision remains the primary treatment modality. The role of surgical margins in the treatment of skin SCC and BCC of the head and neck remains a subject of ongoing debate. Clear definitions and guidelines regarding adequate surgical margins, as well as their impact on recurrence rates and overall outcomes, are critical for improving clinical management. This systematic review aims to evaluate the current literature on the definitions of surgical margins for SCC and BCC of the head and neck, as well as their impact on local recurrence, disease free survival, and other patient-centred outcomes.

Major salivary gland malignancies (MSGM) are a rare and heterogeneous group of tumours accounting for 1-5% of all head and neck cancers. When feasible, surgical removal with negative margins is the preferred treatment, reserving adjuvant radiotherapy for adverse clinicopathological features such as high-grade, advanced-stage, extranodal extension, lympho-vascular invasion, perineural invasion, and positive margins. This systematic review aims to evaluate the current literature on the definition of negative and close margins for MSGM, their impact on loco-regional recurrence (LRR), disease-free (DFS), and overall survival (OS), and their implications in the choice of multimodal therapies.

Hypopharyngeal squamous cell carcinoma is an aggressive malignancy with poor prognosis due to frequently late-stage presentation and intrinsic anatomical complexity. Surgery remains a key treatment, and resection margins are crucial for local control and survival. However, achieving adequate margins is challenging due to submucosal tumour spread and common "skip lesions". This systematic review examines the impact of positive and close margins on oncological outcomes and their role in treatment planning.

Over the past two decades there has been a strategic shift in treating laryngeal cancer, with an increasing emphasis on preserving the anatomical structure and function of the larynx, even in cases of intermediate or advanced stages of disease. Open partial horizontal laryngectomies (OPHL) are widely adopted to spare the physiological functions of the larynx while achieving good oncological control. Positive, close or narrow surgical margins remain a critical prognostic factor, with their impact varying by tumour location and laryngeal subsite. This review examines the influence of positive margins on survival and the potential need for adjuvant treatments to optimise functional and oncological outcomes.

To evaluate the prognostic significance of surgical margins in patients undergoing transoral laser microsurgery (TLM) for laryngeal squamous cell carcinoma (LSCC).

Nasopharyngeal malignancies are rare heterogenous histologies (nasopharyngeal carcinoma [NPC], minor salivary glands carcinomas, and low-grade papillary nasopharyngeal adenocarcinoma) and a significant proportion of patients experience loco-regional recurrence after primary treatment. Resection margin status is a key prognostic factor that influences recurrence and survival, although definitions and criteria for negative, close, and positive margins remain inconsistent. This systematic review with meta-analysis aimed to summarise the existing definitions of resection margins in the literature and evaluate their impact on clinical outcomes in patients undergoing nasopharyngectomy with a specific focus on NPC.

Surgery remains a cornerstone in treatment of sinonasal malignancies, but the prognostic role of margin status is controversial. This systematic review and meta-analysis evaluated the prognostic significance of surgical margins in sinonasal cancer and their impact on survival, alongside key challenges in its evaluation.

In oropharyngeal squamous cell carcinoma (OPSCC), proper definition of surgical margins may have substantial impact on oncologic outcomes. Minimally-invasive techniques prioritise reduced morbidity, yet open approaches remain significant due to limited large-scale evidence comparing their outcomes with transoral methods. The purpose of the present systematic review was to assess the incidence of positive margins in OPSCC management based on surgical approach (open vs transoral) and the subsequent risk of additional treatments.

The aim of this study is to analyse the impact of surgical margins on survival outcomes for patients with oral cavity squamous cell carcinoma (OCSCC).

The immunological microenvironment in hepatocellular carcinoma (HCC) is characterized by impaired immune responses. Significantly, LAIR-2 levels correlate with immune cell subtype infiltration, T cell exhaustion, and its prognostic potential in HCC. This study aims to assess the diagnostic and prognostic significance of expression levels of Pax8-AS1 and LAIR-2 in patients with HCV and their association with susceptibility to HCC. Pax8-AS1 and LAIR-2 expression levels in the serum of patients were analyzed using reverse transcription-quantitative PCR (RT-PCR), while the efficacy of biomarkers in prognostic prediction was assessed by using bioinformatics. The current research showed that Pax8-AS1 had low expression levels in the blood and a positive correlation with portal vein diameter in HCC, which is predictive of portal vein thrombosis (PVT) development. The expression levels of LAIR-2 were elevated in HCV and HCC cases. In HCC, there was an inverse correlation among LAIR-2 and hematology laboratory tests, albumin, tumor nodules, ascites, and splenomegaly. However, there was a positive correlation among LAIR-2, spleen diameter, AFP, and bilirubin. Pax8-AS1 and LAIR-2 showed remarkable diagnostic efficacy, with sensitivity and specificity values, respectively (p < 0.001) (80%, 80% and 90%, 100%) in HCV and (96.7%, 80% and 93%, 100%) in HCC. LAIR-2 overexpression positively correlates with several critical genes associated with exhausted T cells immune infiltration, T cells, CD4+, and CD8+ T cells. The present data support a novel diagnostic and prognostic function for LAIR2 and PAX8-AS1 in HCC, and its significant association with T cell exhaustion contributes to its promotion in HCC. LAIR-2 detection could provide a new prognosis prediction method, and regulation within T-cell exhaustion, optimizing anti-HCC treatments.

Recent advancements in exosome research have revealed their crucial role in myeloid leukemia, encompassing chronic myeloid leukemia (CML) and acute myeloid leukemia (AML). Exosomes, small extracellular vesicles released by various cells, play a significant role in intercellular communication and impact key cellular processes such as growth, proliferation, angiogenesis, survival, and apoptosis. In leukemia, exosomes contribute to disease progression and therapeutic resistance by facilitating immune evasion, enhancing tumor cell proliferation, and promoting angiogenesis. For instance, exosomes derived from CML cells can transfer drug resistance to sensitive cells, and some exosomes derived from AML patients contain cytokines like TGF-β1 that inhibit immune cell activity. Exosomes also influence tumor organotropism by interacting with extracellular matrix molecules and modifying the tumor microenvironment. Despite their high potential, clinical applications of exosomes are limited. Their natural nanoparticle properties-such as adaptability, biodegradability, low toxicity, and the ability to cross biological barriers-make them promising candidates for targeted drug delivery and personalized medicine. Further research is necessary to scale up exosome production and harness their full therapeutic potential. By integrating advancements in exosome biology with innovative therapeutic strategies, there is significant potential for improved management and treatment of leukemia.