As lung cancer treatment continues to advance, mainstream approaches such as surgery, radiotherapy, chemotherapy, neoadjuvant therapy, targeted therapy and immunotherapy have become widely adopted in clinical practice. However, the efficacy of these methods is still limited and they are associated with significant side effects. In recent years, the pivotal role of the gut microbiota in tumor immune regulation has become increasingly recognized, with its potential impact on tumor immunotherapy emerging as a novel therapeutic focus in lung cancer management. Against this backdrop, fecal microbiota transplantation (FMT) has been proposed as a potential immunomodulatory strategy. It enhances host immune responses and improves the tumor immune microenvironment by regulating the gut microbiota. This paper provides a systematic review of the latest research advances in FMT for lung cancer treatment. Focusing on the relationship between gut microbiota and lung cancer, the therapeutic mechanisms of FMT and clinical application studies, it provides a comprehensive exploration of the challenges and prospects for the use of FMT in lung cancer therapy.
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Lung cancer is the malignant tumor with the highest morbidity and mortality, and it is usually diagnosed with advanced metastasis. Tumor metastasis is an important factor affecting treatment resistance and poor prognosis of lung cancer, among which bone metastasis is a common metastatic pattern of lung cancer and is associated with a particularly dismal prognosis. Meanwhile, bone metastasis frequently causes skeletal-related events such as bone pain, pathological fractures, nerve compression, and hypercalcemia. Exosomes are extracellular vesicles with a diameter of 40-160 nm that are released from the fusion of intracellular multivesicular bodies and the cell membrane. Carrying proteins, lipids, and nucleic acids, they mediate communication between tumor cells and their surrounding matrix, immune cells, and the bone microenvironment. So, it has attracted increasing attention from researchers. This paper aims to summarize and organize the latest research advances on exosomes promoting lung cancer bone metastasis, focusing on their key mechanisms and signaling pathways. These include promoting tumor cells proliferation, invasion and metastasis at the primary lesion, as well as participating in energy metabolism reprogramming, pre-metastatic niche remodeling, immune microenvironment regulation, and interactions with osteocytes, stromal cells, and other cells during distant bone metastasis colonization. In addition, this review analyzes the potential clinical translational value of exosomes in the early diagnosis, treatment, and prognosis of lung cancer bone metastasis.

Lung adenocarcinoma is prone to brain metastasis, and the prognosis of patients is extremely poor. The inhibitor of apoptosis-stimulating protein of p53 (iASPP) protein, encoded by the protein phosphatase 1 regulatory subunit 13-like (PPP1R13L) gene, is a key inhibitor of the p53 pathway and promotes carcinogenesis in various tumors, but its role in brain metastasis of lung adenocarcinoma is unknown. This study aims to analyze the tumor microenvironment characteristics of patients with brain metastasis of lung adenocarcinoma and explore the expression of PPP1R13L in brain metastasis tissues and its clinical significance by single-cell sequencing and clinical sample analysis.

Brain tissues from 4 patients with lung adenocarcinoma brain metastasis and 2 patients with oligodendroglioma (ODG) were collected from the Affiliated Tumor Hospital of Xinjiang Medical University from January 2014 to December 2024 for single-cell sequencing. The tumor microenvironment was analyzed by combining single-cell sequencing data from 4 lung adenocarcinoma samples and 4 normal lung tissue samples from public databases. Additionally, clinical data and paraffin sections of 50 patients with lung adenocarcinoma brain metastasis in this hospital were collected, and immunohistochemistry was used to assess iASPP expression and its association with clinicopathologic features and patient outcome.

Compared with the ODG and lung adenocarcinoma groups, the specific epithelial cells in the lung adenocarcinoma brain metastasis group were mainly enriched in oxidative phosphorylation, apoptosis, hypoxia, and p53 pathways. PPP1R13L, as an upregulated differential gene, was highly expressed in the specific epithelial cell subpopulation of the brain metastasis group; the interaction between PPP1R13L-positive cells and fibroblasts was significant, activating cell-matrix adhesion related pathways, with the key ligand-receptor pair being collagen type I alpha 1 chain-cluster of differentiation 44 (COL1A1-CD44). Statistical evaluation revealed that smoking (HR=2.543, 95%CI: 1.159-5.583, P=0.020) and high expression of iASPP (HR=3.351, 95%CI: 1.310-8.575, P=0.012) were independent predictors of poor prognosis in lung adenocarcinoma patients with brain metastases.

This study revealed the interaction between epithelial cells and fibroblasts in the microenvironment of lung adenocarcinoma brain metastasis and implicate PPP1R13L as a potential prognostic indicator and actionable target, offering rationale for precision therapy against lung adenocarcinoma brain metastases.

The adenovirus E3 region's immune-modulating genes (gp19K, Adenovirus Death Protein [ADP], E3B) are frequently modified in oncolytic adenoviruses (OAds) through deletion and transgene insertion like granulocyte-macrophage colony-stimulating factor (GM-CSF). However, the synergistic effects of dual-gene deletions on antitumor efficacy and transgene capacity remain unexplored. To address this, we constructed three E3-modified OAds including OAd5-delgp19K (delgp19K), M20 (delgp19K and ADP), M22-0 (delgp19K and E3B), and their GM-CSF-armed derivatives, systematically evaluating the impact of ADP and E3B deletions on viral replication, tumor cell lysis, immune modulation, and in vivo antitumor activity. Key findings revealed that gp19K/ADP deletion OAd prolonged intracellular viral replication, creating a "viral bomb" effect that delayed cell lysis, evading anti-adenovirus antibodies, sustained GM-CSF expression, and culminating in superior tumor suppression. Gp19K/E3B deletion OAd accelerated viral dissemination but triggered rapid antibody-mediated clearance in immunocompetent hosts, resulting in transient GM-CSF expression and diminished therapeutic persistence. In immunocompetent Syrian hamster Hap-T1 subcutaneous tumor models, gp19K/ADP deletion OAd demonstrated potent tumor inhibition, durable immune microenvironment remodeling, robust viral replication, and evading anti-adenovirus antibodies. These results underscore the critical role of coordinated gp19K/ADP deletion in optimizing viral replication, transgene expression, and immune evasion, providing a strategic framework for engineering next-generation OAds.

Lysozyme (LYZ) is a naturally occurring antimicrobial protein first discovered in the 1920s. As a key component of innate immunity, its antimicrobial effects and immunomodulatory functions in bacterial defence have been extensively characterized. However, emerging evidence since the 1950s has revealed its complex involvement in tumour progression, with conflicting reports of both tumour-suppressive and tumour-promoting effects across different cancer types. A critical knowledge gap remains in understanding the mechanistic basis for this duality, exacerbated by reliance on single-omics approaches and small cohorts in previous studies. This review focuses on mammalian C-type LYZ (referred to as LYZ hereafter unless specified) and integrates multi-omics data (transcriptomics and proteomics) with clinical and mechanistic research to systematically dissect its dual roles in cancer. By analysing cross-cancer heterogeneity through multi-omics perspectives, we emphasize its dual promise as both a prognostic biomarker and an actionable therapeutic target, aiming to provide new insights for precision oncology. KEY POINTS: LYZ is a multi-functional secreted factor that encompasses both antibacterial and immunomodulatory functions. Emerging evidence highlights its complex role in tumour progression by directly influencing tumour cells and modulating the immune microenvironment. LYZ is a promising potential biomarker and therapeutic target in some cancers.

A 9-year-old neutered male miniature schnauzer was referred to our facility with polyuria, polydipsia, persistent hypercalcemia, hypophosphatemia, and elevated parathyroid hormone-related protein. Dual-energy computed tomography (DECT) imaging revealed a mass in the left anal gland (LAG) and enlargement of the left medial iliac lymph node (LML) and the left internal iliac lymph node (LIL). The mass was surgically removed, and the histopathological diagnosis was anal sac gland adenocarcinoma, with metastasis to the LML and LIL. The pathological findings were concordant with those obtained from our evaluation of the spectral Hounsfield unit curve and iodine concentration DECT imaging. DECT analysis may be useful for identifying metastatic lymph nodes.

ADAMTS-2 is a key extracellular matrix (ECM) remodeling enzyme increasingly implicated in osteosarcoma biology. Although ADAMTS-2 is known to participate in collagen processing and ECM turnover, the upstream inflammatory cues and transcriptional mechanisms regulating its expression in osteosarcoma remain unclear. Tumor necrosis factor-α (TNF-α), a dominant pro-inflammatory cytokine within the osteosarcoma microenvironment, represents a strong candidate regulator due to its ability to activate several pathways. This study aimed to elucidate the TNF-α-ADAMTS-2 regulatory axis at mechanistic levels.

Gene expression profiling revealed that ADAMTS-2 is significantly upregulated in osteosarcoma tissues compared with normal bone and is associated with ECM disassembly and collagen fibril organization pathways. Functional assays in Saos-2 cells demonstrated that TNF-α stimulation markedly increased ADAMTS-2 mRNA (~ 17-fold) and protein levels (~ twofold). Promoter activity assays showed strong TNF-α-mediated activation, with the highest induction in the - 180/ + 112 region. Pharmacological inhibition experiments revealed that MEK, PI3K, JNK, and NF-κB pathways are all required for TNF-α-induced ADAMTS-2 transcription. In silico motif analysis identified STAT3 and NF-κB binding elements within the promoter, and electrophoretic mobility shift assays supported the interaction of these transcription factors with specific promoter regions.

This study provides the first mechanistic evidence that TNF-α regulates ADAMTS-2 expression through the coordinated activation of multiple signaling pathways and the engagement of STAT3 and NF-κB transcription factors at the promoter. These findings uncover a previously uncharacterized inflammatory regulatory axis linking TNF-α signaling to ECM remodeling and highlight ADAMTS-2 as a potential mediator of osteosarcoma progression.

The regulation of the programmed cell death protein 1 (PD-1) gene, PDCD1, has been widely explored at transcription and posttranslational levels in T cell function and tumor immune evasion. However, the mechanism for PDCD1 dysregulation at the posttranscriptional level remains largely unknown. Here, we identify protein arginine methyltransferase 5 (PRMT5) as a RNA binding protein in a methyltransferase activity-independent manner, which promotes PDCD1 decay with WD repeat domain 77 protein (WDR77) and Argonaute2. Furthermore, the type-I IFN/STAT1 pathway transcriptionally activates PRMT5 and WDR77, thus enhancing PRMT5/WDR77 binding on a conserved AU-rich element of PDCD1 3' UTR. Functionally, conditional knockout of either PRMT5 or WDR77 in T cells disrupts T cell effector function and sensitizes the tumors to anti-PD-1 therapy. Clinically, PRMT5 and WDR77 expression in tumor-infiltrating T cells are negatively correlated with PDCD1 expression and renders tumors resistant to PD-1-targeted immunotherapy. Moreover, fludarabine targeting STAT1 in combination with anti-PD-1 has a synergetic effect on suppressing tumor growth in mice. Overall, this study reveals that the RNA binding-dependent function of PRMT5 regulates PDCD1 and T cell effector function with WDR77 and identifies potential combinatorial therapeutic strategies for enhancing antitumor efficacy.

Turcot syndrome (TS) is an extremely rare genetic disorder characterized by the concurrent occurrence of primary brain tumors and colorectal cancer. The prognosis for patients with TS is typically poor. A 57-year-old man with TS who developed recurrent glioblastoma and had a family history of colon cancer is reported. In 2022, the patient underwent robot-assisted stereotactic surgery for the resection of a central nervous system (CNS) tumor. Molecular genetic analysis identified microsatellite instability in the DNA mismatch repair (MMR) gene, confirming the diagnosis of TS. Additional mutations in the ATM and TP53 genes were also detected, which are rarely associated with TS. Despite treatment with the Stupp regimen, the patient experienced acute neurological deterioration, ultimately resulting in death 15 months after the onset of symptoms. Molecular diagnostics play a crucial role in guiding appropriate care and management for patients with TS. Early diagnosis, genetic testing, and preventive measures are essential for the effective management of this condition.

Neuromuscular diseases (NMDs) are reported to have increased obstructive apnoea/hypopnoea during rapid eye movement (REM) sleep; however, the prevalence of REM-related obstructive sleep apnoea (OSA) and its clinical correlates in NMD remain undefined. We evaluated REM sleep, REM-related OSA frequency, and associated with demographic and clinical factors.

We retrospectively evaluated patients with NMDs who underwent polysomnography (PSG) between 2015 and 2024. Demographic data, morning arterial blood gases, spirometry and PSG data were collected. REM-related OSA required AHI ≥ 5 events/hour, REM-to-non-REM (NREM) AHI ≥ 2, and REM ≥ 30 min; REM-isolated additionally required NREM AHI < 5 events/hour. Patients with OSA who did not meet the criteria for REM-related OSA were classified as having NREM-related OSA.

Among 290 patients, OSA was present in 87.6% (254/290). REM sleep duration was markedly reduced (11.8 ± 8.0%; 46.8 ± 32.2 min), and 30.0% of patients had REM duration < 30 min. Among OSA with REM ≥ 30 min (n = 182), 54.4% had REM-related OSA; 25.3% were REM-isolated. Compared with NREM-related OSA, the REM-related group exhibited more frequent female sex (p = 0.015), hypertension (p = 0.020), and depression (p = 0.025). In multivariable analysis, REM-related OSA was independently associated with morning hypercapnia (aOR 4.889; 95%CI 1.885-12.680), forced vital capacity (FVC) < 50% and/or ≥ 20% upright-to-supine decline (aOR 3.847; 95%CI 1.085-13.642), and mild OSA (aOR 3.461; 95%CI 1.509-7.937).

Despite the marked reduction in REM sleep in NMDs, OSA, and particularly REM-related OSA, is common. In the REM-related OSA group, morning hypercapnia and FVC decline were more frequent. These observations suggest that REM-stage characteristics may be predictive of subsequent chronic respiratory failure.