Basement membrane-related lncRNA signature for the prognosis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the main type of primary liver cancer. This study aimed to develop a basement membrane (BM) related lncRNAs risk signature to evaluate the prognosis of HCC patients. We screened differentially expressed BM-related lncRNAs (DE-BMRlncRNAs) for risk evaluation, and identified six DE-BMRlncRNAs (AC072054.1, NUP50-DT, AC026412.3, AC109322.2, POLH-AS1 and LINC00595) for prognostic risk signature. HCC patients were divided to high or low risk according to median risk score. Our prognostic model predicted that patients with higher risk score had worse prognosis. We also created a nomogram to assist clinical decision-making according to risk score and clinicopathological features. Meanwhile, we confirmed the expression of six lncRNAs in HCC tissue and cells. POLH-AS1 knockdown inhibited the migration and invasion of HCC cells. In conclusion, we established a predictive model based on BMRlncRNAs to predict the prognosis of HCC. Our findings offer a rationale to further explore BM-related biomarkers for HCC.

Potential clinical application of microRNAs in bladder cancer.

Bladder cancer (BC) is the tenth most prevalent malignancy globally, presenting significant clinical and societal challenges because of its high incidence, rapid progression, and frequent recurrence. Presently, cystoscopy and urine cytology serve as the established diagnostic methods for BC. However, their efficacy is limited by invasive nature and low sensitivity. Therefore, the development of highly specific biomarkers and effective non-invasive detection strategies is imperative for achieving a precise and timely diagnosis of BC, as well as for facilitating an optimal tumor treatment and an improved prognosis. microRNAs (miRNAs), short noncoding RNA molecules spanning around 20-25 nucleotides, are implicated in the regulation of diverse carcinogenic pathways. Substantially altered miRNAs form robust functional regulatory networks that exert a notable influence on the tumorigenesis and progression of BC. Investigations into aberrant miRNAs derived from blood, urine, or extracellular vesicles indicate their potential roles as diagnostic biomarkers and prognostic indicators in BC, enabling miRNAs to monitor the progression and predict the recurrence of the disease. Simultaneously, the investigation centered on miRNA as a potential therapeutic agent presents a novel approach for the treatment of BC. This review provides a comprehensive analysis of the biological roles of miRNAs in tumorigenesis and progression, and systematically summarizes the potential as diagnosis and prognosis biomarkers as well as therapeutic targets for BC. Additionally, we evaluate the progress made in laboratory techniques within this field and discuss the prospects.

Assessment of urine sample collection and processing variables for extracellular vesicle-based proteomics.

Extracellular vesicles (EVs) in urine are a promising source for developing non-invasive biomarkers. However, urine concentration and content are highly variable and dynamic, and actual urine collection and handling often is nonideal. Furthermore, patients such as those with prostate diseases have challenges in sample collection due to difficulties in holding urine at designated time points. Here, we simulated the actual situation of clinical sample collection to examine the stability of EVs in urine under different circumstances, including urine collection time and temporary storage temperature, as well as daily urine sampling under different diet conditions. EVs were isolated using functionalized EVtrap magnetic beads and characterized by nanoparticle tracking analysis (NTA), western blotting, electron microscopy, and mass spectrometry (MS). EVs in urine remained relatively stable during temporary storage for 6 hours at room temperature and for 12 hours at 4 °C, while significant fluctuations were observed in EV amounts from urine samples collected at different time points from the same individuals, especially under certain diets. Sample normalization with creatinine reduced the coefficient of variation (CV) values among EV samples from 17% to approximately 6% and facilitated downstream MS analyses. Finally, based on the results, we applied them to evaluate potential biomarker panels in prostate cancer by data-independent acquisition (DIA) MS, presenting the recommendation that can facilitate biomarker discovery with nonideal handling conditions.

Amplification-Free Analysis of Bladder Cancer MicroRNAs on Wrinkled Silica Nanoparticles with DNA-Functionalized Quantum Dots.

Bladder cancer (BC) occurrence and progression are accompanied by alterations in microRNAs (miRNAs) expression levels. Simultaneous detection of multiple miRNAs contributes to the accuracy and reliability of the BC diagnosis. In this work, wrinkled silica nanoparticles (WSNs) were applied as the microreactor for multiplex miRNAs analysis without enzymes or nucleic acid amplification. Conjugated on the surface of WSNs, the S9.6 antibody was adopted as the universal module for binding DNA/miRNA duplexes, regardless of their sequence. Furthermore, single-stranded DNA (ssDNA) was labeled with quantum dots (QDs) for identifying a given miRNA to form QDs-ssDNA/miRNA, which enabled the specific capture of the corresponding QDs on the wrinkled surface of WSNs. Based on the detection of fluorescence signals that were ultimately focused on WSNs, target miRNAs could be sensitively identified to a femtomolar level (5 fM) with a wide dynamic range of up to 6 orders of magnitude. The proposed strategy achieved high specificity to obviously distinguish single-base mutation sequences and possessed multiplex assay capability. Moreover, the assay exhibited excellent practicability in the multiplex detection of miRNAs in clinical serum specimens.

Fusobacterium nucleatum promotes tumor progression in KRAS p.G12D-mutant colorectal cancer by binding to DHX15.

Fusobacterium nucleatum (F. nucleatum) promotes intestinal tumor growth and its relative abundance varies greatly among patients with CRC, suggesting the presence of unknown, individual-specific effectors in F. nucleatum-dependent carcinogenesis. Here, we identify that F. nucleatum is enriched preferentially in KRAS p.G12D mutant CRC tumor tissues and contributes to colorectal tumorigenesis in Villin-Cre/KrasG12D+/- mice. Additionally, Parabacteroides distasonis (P. distasonis) competes with F. nucleatum in the G12D mouse model and human CRC tissues with the KRAS mutation. Orally gavaged P. distasonis in mice alleviates the F. nucleatum-dependent CRC progression. F. nucleatum invades intestinal epithelial cells and binds to DHX15, a protein of RNA helicase family expressed on CRC tumor cells, mechanistically involving ERK/STAT3 signaling. Knock out of Dhx15 in Villin-Cre/KrasG12D+/- mice attenuates the CRC phenotype. These findings reveal that the oncogenic effect of F. nucleatum depends on somatic genetics and gut microbial ecology and indicate that personalized modulation of the gut microbiota may provide a more targeted strategy for CRC treatment.

Suppression of ZNF205-AS1/EGR4 positive feedback loop attenuates cisplatin resistance of non-small cell lung cancer cells via targeting miR-138-5p/OCT4 pathway.

Background: Long non-coding RNAs (lncRNAs) are frequently reported to involve in the onset and development of non-small cell lung cancer (NSCLC). Cisplatin (DDP) resistance continues to pose a daunting challenge for improving the prognosis of NSCLC patients. The current study intends to elucidate the molecular mechanisms underlying the function of lncRNA ZNF205 AS1/early growth response 4 (EGR4) positive feedback loop in DDP resistance of NSCLC. Methods: A series of assays, including real-time polymerase chain reaction (PCR), western blotting, flow cytometry, and dual-luciferase reporter, were performed to evaluate the effect of ZNF205-AS1/EGR4 loop in the established DDP-resistant A549 cell line and its progenitor A549 cell line. Immunohistochemistry (IHC) technique was conducted to investigate the expression pattern of EGR4 and octamer-binding protein 4 (OCT4) in NSCLC tissues. RNA pull-down assay was carried out to evaluate the interaction between miR-138-5p and EGR4 and OCT4. Transwell assay and wound healing assay was used to evaluate the invasive and migratory potential of cells subject to various treatment. The protein levels of Bcl2, Bax, Cl-caspase 3, Cl-PARP and OCT4 were measured in western blotting assay. Results: The levels of ZNF205-AS1, EGR4 and OCT4 were notably upregulated in post-chemotherapy DDP-resistant lung specimens, as opposed to those pre-chemotherapy, and in A549/DDP cells than the progenitor DDP-sensitive A549 cells. In contrast, the level of miR-138-5p was significantly reduced in A549/DDP cells (P<0.05). Luciferase reporter assay confirmed the interaction between ZNF205-AS1 and miRNA-138-5p. Protein-RNA interaction was validated between miR-138-5p, EGR4 and OCT4. The higher chemosensitivity of DDP-resistant cells induced by the loss-of-function of ZNF205-AS1 could be diminished by a miR-138-5p inhibitor. Conclusions: Our data demonstrated that miR-138-5p/OCT4 functions as a downstream effector of the ZNF205-AS1/EGR4 positive feedback loop and mediates resistance of NSCLC cells to DDP. Our work sheds light on the therapeutic strategies for NSCLC with DDP chemoresistance.

A cross-disorder study to identify causal relationships, shared genetic variants, and genes across 21 digestive disorders.

Digestive disorders are a significant contributor to the global burden of disease and seriously affect human quality of life. Research has already confirmed the presence of pleiotropic genetic loci among digestive disorders, and studies have explored shared genetic factors among pan-cancers, including various malignant digestive disorders. However, most cross-phenotype studies within the digestive tract system have been limited to a few traits, with no systematic coverage of common benign and malignant digestive disorders. Here, we analyzed data from the UK Biobank to investigate 21 digestive disorders, exploring the genetic correlations and causal relationships between diseases, as well as the common genetic factors and potential biological pathways driving these relationships. Our findings confirmed the extensive genetic correlation and causal relationship between digestive disorders, providing important insights into the genetic etiology, causality, disease prevention, and clinical treatment of diseases.

Colorectal cancer-associated T cell receptor repertoire abnormalities are linked to gut microbiome shifts and somatic cell mutations.

As with many diseases, tumor formation in colorectal cancer (CRC) is multifactorial and involves immune, environmental factors and various genetics that contribute to disease development. Accumulating evidence suggests that the gut microbiome is linked to the occurrence and development of CRC, and these microorganisms are important for immune maturation. However, a systematic perspective integrating microbial profiling, T cell receptor (TCR) and somatic mutations in humans with CRC is lacking. Here, we report distinct features of the expressed TCRß repertoires in the peripheral blood of and CRC patients (n = 107) and healthy donors (n = 30). CRC patients have elevated numbers of large TCRß clones and they have very low TCR diversity. The metagenomic sequencing data showed that the relative abundance of Fusobacterium nucleatum (F. nucleatum), Escherichia coli and Dasheen mosaic virus were elevated consistently in CRC patients (n = 97) compared to HC individuals (n = 30). The abundance of Faecalibacterium prausnitzii and Roseburia intestinalis was reduced in CRC (n = 97) compared to HC (n = 30). The correlation between somatic mutations of target genes (16 genes, n = 79) and TCR clonality and microbial biomarkers in CRC had been investigated. Importantly, we constructed a random forest classifier (contains 15 features) based on microbiome and TCR repertoires, which can be used as a clinical detection method to screen patients for CRC. We also analysis of F. nucleatum-specific TCR repertoire characteristics. Collectively, our large-cohort multi-omics data aimed to identify novel biomarkers to inform clinical decision-making in the detection and diagnosis of CRC, which is of possible etiological and diagnostic significance.

Destroying pathogen-tumor symbionts synergizing with catalytic therapy of colorectal cancer by biomimetic protein-supported single-atom nanozyme.

The crucial role of intratumoral bacteria in the progression of cancer has been gradually recognized with the development of sequencing technology. Several intratumoral bacteria which have been identified as pathogens of cancer that induce progression, metastasis, and poor outcome of cancer, while tumor vascular networks and immunosuppressive microenvironment provide shelters for pathogens localization. Thus, the mutually-beneficial interplay between pathogens and tumors, named "pathogen-tumor symbionts", is probably a potential therapeutic site for tumor treatment. Herein, we proposed a destroying pathogen-tumor symbionts strategy that kills intratumoral pathogens, F. nucleatum, to break the symbiont and synergize to kill colorectal cancer (CRC) cells. This strategy was achieved by a groundbreaking protein-supported copper single-atom nanozyme (BSA-Cu SAN) which was inspired by the structures of native enzymes that are based on protein, with metal elements as the active center. BSA-Cu SAN can exert catalytic therapy by generating reactive oxygen species (ROS) and depleting GSH. The in vitro and in vivo experiments demonstrate that BSA-Cu SAN passively targets tumor sites and efficiently scavenges F. nucleatum in situ to destroy pathogen-tumor symbionts. As a result, ROS resistance of CRC through elevated autophagy mediated by F. nucleatum was relieved, contributing to apoptosis of cancer cells induced by intracellular redox imbalance generated by BSA-Cu SAN. Particularly, BSA-Cu SAN experiences renal clearance, avoiding long-term systemic toxicity. This work provides a feasible paradigm for destroying pathogen-tumor symbionts to block intratumoral pathogens interplay with CRC for antitumor therapy and an optimized trail for the SAN catalytic therapy by the clearable protein-supported SAN.

Activation of autophagy by in situ Zn2+ chelation reaction for enhanced tumor chemoimmunotherapy.

Chemotherapy can induce a robust T cell antitumor immune response by triggering immunogenic cell death (ICD), a process in which tumor cells convert from nonimmunogenic to immunogenic forms. However, the antitumor immune response of ICD remains limited due to the low immunogenicity of tumor cells and the immunosuppressive tumor microenvironment. Although autophagy is involved in activating tumor immunity, the synergistic role of autophagy in ICD remains elusive and challenging. Herein, we report an autophagy amplification strategy using an ion-chelation reaction to augment chemoimmunotherapy in cancer treatments based on zinc ion (Zn2+)-doped, disulfiram (DSF)-loaded mesoporous silica nanoparticles (DSF@Zn-DMSNs). Upon pH-sensitive biodegradation of DSF@Zn-DMSNs, Zn2+ and DSF are coreleased in the mildly acidic tumor microenvironment, leading to the formation of toxic Zn2+ chelate through an in situ chelation reaction. Consequently, this chelate not only significantly stimulates cellular apoptosis and generates damage-associated molecular patterns (DAMPs) but also activates autophagy, which mediates the amplified release of DAMPs to enhance ICD. In vivo results demonstrated that DSF@Zn-DMSNs exhibit strong therapeutic efficacy via in situ ion chelation and possess the ability to activate autophagy, thus enhancing immunotherapy by promoting the infiltration of T cells. This study provides a smart in situ chelation strategy with tumor microenvironment-responsive autophagy amplification to achieve high tumor chemoimmunotherapy efficacy and biosafety.

Targeting inorganic nanoparticles to tumors using biological membrane-coated technology.

Inorganic nanoparticles have extensively revolutionized the effectiveness of cancer therapeutics due to their distinct physicochemical properties. However, the therapeutic efficiency of inorganic nanoparticles is greatly hampered by the complex tumor microenvironment, patient heterogeneity, and systemic nonspecific toxicity. The biomimetic technology based on biological membranes (cell- or bacteria-derived membranes) is a promising strategy to confer unique characteristics to inorganic nanoparticles, such as superior biocompatibility, prolonged circulation time, immunogenicity, homologous tumor targeting, and flexible engineering approaches on the surface, resulting in the enhanced therapeutic efficacy of inorganic nanoparticles against cancer. Therefore, a greater push toward developing biomimetic-based nanotechnology could increase the specificity and potency of inorganic nanoparticles for effective cancer treatment. In this review, we summarize the recent advances in biological membrane-coated inorganic nanoparticles in cancer precise therapy and highlight the different types of engineered approaches, applications, mechanisms, and future perspectives. The surface engineering of biological membrane can greatly enhance their targeting, intelligence, and functionality, thereby realizing stronger tumor therapy effects. Further advances in materials science, biomedicine, and oncology can facilitate the clinical translation of biological membrane-coated inorganic nanoparticles.

Integrated Analysis of Colorectal Cancer Reveals Cross-Cohort Gut Microbial Signatures and Associated Serum Metabolites.

BACKGROUND & AIMS: Studies have reported abnormal gut microbiota or circulating metabolome associated with colorectal cancer (CRC), but it remains a challenge to capture the CRC-relevant features consistent across geographic regions. This is particularly the problem for metabolic traits of CRC because the analyses generally use different platforms and laboratory methods, which poses a barrier to cross-dataset examination. In light of this, we sought to elucidate the microbial and metabolic signatures of CRC with broad population relevance. METHODS: In this integrated metagenomic (healthy controls [HC], n = 91; colorectal adenoma [CRA], n = 63; CRC, n = 71) and metabolomic (HC, n = 34; CRA, n = 31; CRC, n = 35) analysis, CRC-associated features and microbe-metabolite correlations were first identified from a Shanghai cohort. A gut microbial panel was trained in the in-house cohort and cross-validated in 7 published metagenomic datasets of CRC. The in-house metabolic connections to the cross-cohort microbial signatures were used as evidence to infer serum metabolites with potentially external relevance. In addition, a combined microbe-metabolite panel was produced for diagnosing CRC or adenoma. RESULTS: CRC-associated alterations were identified in the gut microbiome and serum metabolome. A composite microbe-metabolite diagnostic panel was developed and yielded an area under the curve of 0.912 for adenoma and 0.994 for CRC. We showed that many CRC-associated metabolites were linked to cross-cohort gut microbiome signatures of the disease, including CRC-enriched leucylalanine, serotonin, and imidazole propionate; and CRC-depleted perfluorooctane sulfonate, 2-linoleoylglycerol (18:2), and sphingadienine. CONCLUSIONS: We generated cross-cohort metagenomic signatures of CRC, some of which linked to in-house CRC-associated serum metabolites. The microbial and metabolic shifts may have wide population relevance.

Simultaneous Detection of Bladder Cancer Exosomal MicroRNAs Based on Inorganic Nanoflare and DNAzyme Walker.

Bladder cancer (BC) is one of the most common cancers in the world, with high morbidity and mortality. It is essential to develop a non-invasive, highly accurate, and simple method for BC diagnosis. This work proposed a fluorescent biosensor based on inorganic nanoflares combined with a DNAzyme walker for the simultaneous detection of BC exosomal microRNAs (miRNAs). This biosensor was constructed on the Au nanoparticle (AuNP) modified with the carbon dot (CD)-labeled substrates and DNAzyme strands (AuNP@CDs inorganic nanoflares-DNAzyme, APCD). In the presence of target miRNAs, DNAzyme was activated and then cleaved the CD-labeled substrates and automatically walked along the AuNP, allowing fluorescence recovery. Due to the structure and functional composition, the APCD biosensors demonstrated high sensitivity and specificity, with the reached limit of detection for a single miRNA at the femtomolar level and wide linear range from 50 fM to 10 nM. Furthermore, the simultaneous analysis of BC-related exosomal miR-133b and miR-135b in clinical serum specimens was achieved and consistent with qRT-PCR, suggesting it is a potential method for the diagnosis of BC and other cancers.

Detection of serum EphA2-EVs for pancreatic cancer diagnosis by light initiated chemiluminescent assay.

Pancreatic cancer has led to an extremely high mortality rate because of its insidious onset and lack of early clinical symptoms. Effective early diagnosis is essential to improve the treatment of pancreatic cancer. Tumor-secreted extracellular vesicles (EVs) have attracted great interest as potential tumor biomarkers. However, most of the methods for detecting serum EVs have some general problems such as cumbersome, time-consuming extraction steps, and high cost, which limit greatly the research on cancer detection based on EVs. Herein, we report a light-initiated chemiluminescent assay (LICA) method using photosensitive beads for direct detection of EVs in serum enriched with ephrin type-A receptor 2 (EphA2), which show high expression in pancreatic cancer patients. Combining with a serum biomarker CA19-9, pancreatic cancer patients could be distinguished rapidly by sensitive detection of EphA2-EVs from serum without any purification. This developed method could be extended to improve the diagnosis efficiency for other cancers and gain an insight into EV detection.

Development and Validation of a 18F-FDG PET-Based Radiomic Model for Evaluating Hypermetabolic Mediastinal-Hilar Lymph Nodes in Non-Small-Cell Lung Cancer.

BACKGROUND: Accurate evaluation of lymph node (LN) status is critical for determining the treatment options in patients with non-small cell lung cancer (NSCLC). This study aimed to develop and validate a 18F-FDG PET-based radiomic model for the identification of metastatic LNs from the hypermetabolic mediastinal-hilar LNs in NSCLC. METHODS: We retrospectively reviewed 259 patients with hypermetabolic LNs who underwent pretreatment 18F-FDG PET/CT and were pathologically confirmed as NSCLC from two centers. Two hundred twenty-eight LNs were allocated to a training cohort (LN = 159) and an internal validation cohort (LN = 69) from one center (7:3 ratio), and 60 LNs were enrolled to an external validation cohort from the other. Radiomic features were extracted from LNs of PET images. A PET radiomics signature was constructed by multivariable logistic regression after using the least absolute shrinkage and selection operator (LASSO) method with 10-fold cross-validation. The PET radiomics signature (model 1) and independent predictors from CT image features and clinical data (model 2) were incorporated into a combined model (model 3). A nomogram was plotted for the complex model, and the performance of the nomogram was assessed by its discrimination, calibration, and clinical usefulness. RESULTS: The area under the curve (AUC) values of model 1 were 0.820, 0.785, and 0.808 in the training, internal, and external validation cohorts, respectively, showing good diagnostic efficacy for lymph node metastasis (LNM). Furthermore, model 2 was able to discriminate metastatic LNs in the training (AUC 0.780), internal (AUC 0.794), and external validation cohorts (AUC 0.802), respectively. Model 3 showed optimal diagnostic performance among the three cohorts, with an AUC of 0.874, 0.845, and 0.841, respectively. The nomogram based on the model 3 showed good discrimination and calibration. CONCLUSIONS: Our study revealed that PET radiomics signature, especially when integrated with CT imaging features, showed the ability to identify true and false positives of mediastinal-hilar LNM detected by PET/CT in patients with NSCLC, which would help clinicians to make individual treatment decisions.

Alterations, Interactions, and Diagnostic Potential of Gut Bacteria and Viruses in Colorectal Cancer.

Gut microbiome alteration was closely associated with colorectal cancer (CRC). Previous studies had demonstrated the bacteria composition changes but lacked virome profiles, trans-kindom interactions, and reliable diagnostic model explorations in CRC. Hence, we performed metagenomic sequencing to investigate the gut microbiome and microbial interactions in adenoma and CRC patients. We found the decreased microbial diversity in CRC and revealed the taxonomic alterations of bacteria and viruses were highly associated with CRC at the species level. The relative abundance of oral-derived species, such as Fusobacterium nucleatum, Fusobacterium hwasookii, Porphyromonas gingivalis, and Bacteroides fragilis, increased. At the same time, butyrate-producing and anti-inflammatory microbes decreased in adenoma and CRC by non-parametric Kruskal-Wallis test. Despite that, the relative abundance of Escherichia viruses and Salmonella viruses increased, whereas some phages, including Enterobacteria phages and Uncultured crAssphage, decreased along with CRC development. Gut bacteria was negatively associated with viruses in CRC and healthy control by correlation analysis (P=0.017 and 0.002, respectively). Viruses were much more dynamic than the bacteria as the disease progressed, and the altered microbial interactions were distinctively stage-dependent. The degree centrality of microbial interactions decreased while closeness centrality increased along with the adenoma to cancer development. Uncultured crAssphage was the key bacteriophage that enriched in healthy controls and positively associated with butyrate-producing bacteria. Diagnostic tests based on bacteria by random forest confirmed in independent cohorts showed better performance than viruses for CRC. In conclusion, our study revealed the novel CRC-associated bacteria and viruses that exhibited specific differences and intensive microbial correlations, which provided a reliable diagnostic panel for CRC.

Fusobacterium Nucleatum Promotes the Development of Colorectal Cancer by Activating a Cytochrome P450/Epoxyoctadecenoic Acid Axis via TLR4/Keap1/NRF2 Signaling.

Emerging research has revealed regulation of colorectal cancer metabolism by bacteria. Fusobacterium nucleatum (Fn) plays a crucial role in the development of colorectal cancer, however, whether Fn infection modifies metabolism in patients with colorectal cancer remains unknown. Here, LC-MS/MS-based lipidomics identified the upregulation of cytochrome P450 monooxygenases, primarily CYP2J2, and their mediated product 12,13-EpOME in patients with colorectal cancer tumors and mouse models, which increased the invasive and migratory ability of colorectal cancer cells in vivo and in vitro by regulating the epithelial-mesenchymal transition (EMT). Metagenomic sequencing indicated a positive correlation between increased levels of fecal Fn and serum 12,13-EpOME in patients with colorectal cancer. High levels of CYP2J2 in tumor tissues also correlated with high Fn levels and worse overall survival in patients with stage III/IV colorectal cancer. Moreover, Fn was found to activate TLR4/AKT signaling, downregulating Keap1 and increasing NRF2 to promote transcription of CYP2J2. Collectively, these data identify that Fn promotes EMT and metastasis in colorectal cancer by activating a TLR4/Keap1/NRF2 axis to increase CYP2J2 and 12,13-EpOME, which could serve as clinical biomarkers and therapeutic targets for Fn-infected patients with colorectal cancer. SIGNIFICANCE: This study uncovers a mechanism by which Fusobacterium nucleatum regulates colorectal cancer metabolism to drive metastasis, suggesting the potential biomarker and therapeutic utility of the CYP2J2/12,13-EpOME axis in Fn-infected patients.

Long non-coding RNA linc00665 inhibits CDKN1C expression by binding to EZH2 and affects cisplatin sensitivity of NSCLC cells.

Long non-coding RNAs (lncRNAs) can play significant regulatory roles in cells that affect the development and acquired drug resistance of lung cancer. Herein, we report that lncRNA linc00665 is significantly upregulated in non-small cell lung cancer (NSCLC) tissues compared with adjacent normal tissues. linc00665 affects the sensitivity of NSCLC cells to the chemotherapy drug cisplatin (DDP), making it a potential target for the treatment of NSCLC. Functional experiments showed that linc00665 enhanced the proliferation and migration of NSCLC cells in vivo and in vitro, and knocking down linc00665 could enhance the drug sensitivity of NSCLC cells to DDP. Further work revealed that linc00665 could recruit enhancer of zeste homolog 2 (EZH2) to the promoter region of cyclin-dependent kinase inhibitor 1C (CDKN1C) to inhibit its transcription and thus carry out its tumorigenic role. In conclusion, our study elucidated the carcinogenic role of the linc00665-EZH2-CDKN1C axis in NSCLC tumors and its ability to influence the sensitivity of these tumors to DDP. These results suggest that linc00665 may be a potential diagnostic marker and therapeutic target in NSCLC, and they also provide a new direction for the development of clinical reversal methods for acquired drug resistance in patients with NSCLC.

Study on PD-L1 Expression in NSCLC Patients and Related Influencing Factors in the Real World.

PD-L1 is one of the current biomarkers for immune checkpoint inhibitor (ICI) therapy in patients with non-small-cell lung cancer. However, the expression of PD-L1 in the real world and its related influencing factors remain unclear. We want to observe the expression of PD-L1 in the real world and study the related influencing factors through the collection and analysis of clinical data. R software (version 4.0) was used to perform data analysis and the "corplot" package for correlation analysis. A total of 296 individuals (mean [SD] age, 67 [9] years; 23%female) were assessed. According to the expression amount of PD-L1, the cohort was divided into low nonexpression group (PD-L1 < 1%, 26.7%), low-expression group (1% ≤ PD-L1 < 50%, 49.3%), and high-expression group (PD-L1 ≥ 50%, 23.5%). Age, gender, underlying diseases, smoking status, and PD-L1 expression level were not statistically significant. We found that the expression of PD-L1 was correlated with serum albumin (P < 0.05) and pathological type (P < 0.05) and had a negative correlation with EGFR mutation but did not correlate with gender, age, smoking status, combined with underlying diseases, tumor stage, whether it was initially treated or not, sampling site, specimen type, specimen storage time, R-IFN, CD4, CD8, NLR, CRP, and LDH. The present findings indicated that serum albumin, pathological type, and EGFR mutations are associated with PD-L1 expression in patients with NSCLC, which may provide a new basis for individualized immunotherapy and need further study to confirm. The results of this study help to further reveal the actual expression of PD-L1 in non-small-cell lung cancer patients with real events.

Response to Afatinib in a Patient with NSCLC Harboring Novel EGFR Exon 20 Insertion Mutations.

PURPOSE: Most epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations are resistant to tyrosine kinase inhibitors (TKIs). While some non-small cell lung cancer (NSCLC) patients harboring special subtypes of EGFR ex20ins still achieved clinical response after TKIs treatment, identifying special subtypes of EGFR ex20ins is helpful to find out NSCLC patients who can respond to TKIs. CASE PRESENTATION: A 71-year-old non-smoker Chinese female was diagnosed with advanced lung adenocarcinoma harboring EGFR ex20ins (N771delinsKG). The patient received first-line afatinib (40 mg/day) therapy and a significant and substantial reduction in tumor size was observed subsequently. According to RESIST 1.1, a radiological partial response was achieved. The final progression-free survival was 10 months. CONCLUSION: This is the first published case report of EGFR N771delinsKG lung adenocarcinoma, which highlighted the heterogeneity of clinical response to TKIs for EGFR ex20ins-mutant NSCLC. Such results need to be further investigated in prospective studies.