Harnessing pseudogenes for lung cancer: A novel epigenetic target in diagnosis, prognosis and treatment.

Pseudogenes are abundantly present in the human genome and are often thought of as nonfunctional nucleotide sequences, but a growing body of research suggests that pseudogenes can play important biological roles through a variety of pathways, and can be involved in the development of cancer. Lung cancer is one of the most prevalent cancers in the world and it is crucial to find new therapeutic strategies for the treatment of lung cancer. In recent years, studies on the effects of pseudogenes on lung carcinogenesis have increased rapidly.

circUBE2G1 interacts with hnRNPU to promote VEGF-C-mediated lymph node metastasis of lung adenocarcinoma.

Background: Patients with lymph node(LN)metastasis-positive Lung adenocarcinoma(LUAD)suffer from a significantly reduced five-year survival rate. Increasing evidence indicates circular RNAs(circRNAs)play crucial roles in regulating cancer progression. However, the specific regulatory mechanisms of circRNAs in the LN metastasis of LUAD have not been fully explored.

The role of FOXK2-FBXO32 in breast cancer tumorigenesis: Insights into ribosome-associated pathways.

Objective: To search for a new biomarker that can predict the efficacy and prognosis of tumor immunotherapy.

Method: FOXK2 genes were analyzed using single-cell sequencing in pan-cancer bulk RNA-seq from the TCGA database. We used algorithms to predict their immune infiltration.

FAT4 Mutation is Related to Tumor Mutation Burden and Favorable Prognosis in Gastric Cancer.

Objective: This study aimed to investigate the frequently mutated genes in Gastric Cancer (GC), assess their association with Tumor Mutation Burden (TMB) and the patients' survival, and identify the potential biomarkers for tailored therapy.

Methods: Simple somatic mutation data of GC were collected from the TCGA and ICGC databases. The high-frequency mutated genes were identified from both datasets.

The impact of tertiary lymphoid structures on tumor prognosis and the immune microenvironment in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a common malignancy whose prognosis and treatment outcome are influenced by many factors. Some studies have found that tertiary lymphoid structures (TLSs) in cancer may contribute to prognosis and the prediction of immunotherapy efficacy However, the combined role of TLSs in NSCLC remains unclear. We accessed The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to obtain mRNA sequencing data and clinical information as the TCGA cohort, and used our own sample of 53 advanced NSCLC as a study cohort.

The ATP-bound inward-open conformation of ABCC4 reveals asymmetric ATP binding for substrate transport.

The multidrug resistance-associated protein (MRP) ABCC4 facilitates substrate transport across the cytoplasmic membrane, crucial for normal physiology and mediating multidrug resistance in tumor cells. Despite intensive studies on MRPs, ABCC4's transport mechanism remains incompletely understood. In this study, we unveiled an inward-open conformation with an ATP bound to degenerate NBD1.

A functional variant rs10409772 in FUT6 promoter regulates colorectal cancer progression through PKA/CREB signaling.

Fucosyltransferase 6 (FUT6) is overexpressed in colorectal cancer tissue according to TCGA samples and immunohistochemistry results of a tissue microarray. FUT6 effects cell migration, tumor formation and proliferation of colorectal cancer cells in different essays. FUT6 promotes cancer cell proliferation in vitro and colorectal tumorigenesis in vivo by upregulating PKA/CREB pathway activation.

An anoikis-related lncRNA signature may predict the prognosis, immune infiltration, and drug sensitivity in esophageal cancer.

Background: Esophageal cancer (EC) is a prevalent malignancy with heterogeneous outcomes. This study explores the significance of anoikis-related long non-coding RNAs (lncRNAs) in EC, aiming to unravel their molecular roles and clinical implications.

Methods: Transcriptome and clinical data were obtained from TCGA database for EC samples.

Emerging roles of FOXK2 in cancers and metabolic disorders.

FOXK2, a member of the Forkhead box K (FOXK) transcription factor family, is widely expressed in various tissues and organs throughout the body. FOXK2 plays crucial roles in cell proliferation, differentiation, autophagy, nucleotide biosynthesis, DNA damage response, and aerobic glycolysis. Although FOXK2 is recognized as an oncogene in colorectal cancer and hepatocellular carcinoma, it acts as a tumor suppressor in breast cancer, cervical cancer, and non-small cell lung cancer (NSCLC).

The proportion of tumour stroma predicts response to treatment of immune checkpoint inhibitor in combination with chemotherapy in patients with stage IIIB-IV non-small cell lung cancer.

Aims: Immunotherapy has brought a new era to cancer treatment, yet we lack dependable predictors for its effectiveness. This study explores the predictive significance of intratumour stroma proportion (iTSP) for treatment success and prognosis in non-small cell lung cancer (NSCLC) patients undergoing treatment with immune check-point inhibitors (ICIs) together with chemotherapy.

Methods And Results: We retrospectively collected data from patients with unresectable stage IIIB-IV NSCLC who were treated with first-line ICIs and chemotherapy.

Deacylases-structure, function, and relationship to diseases.

Reversible S-acylation plays a pivotal role in various biological processes, modulating protein functions such as subcellular localization, protein stability/activity, and protein-protein interactions. These modifications are mediated by acyltransferases and deacylases, among which the most abundant modification is S-palmitoylation. Growing evidence has shown that this rivalrous pair of modifications, occurring in a reversible cycle, is essential for various biological functions.

Emerging mechanisms of ferroptosis and its implications in lung cancer.

Lung cancer is one of the most common malignancies and has the highest number of deaths among all cancers. Despite continuous advances in medical strategies, the overall survival of lung cancer patients is still low, probably due to disease progression or drug resistance. Ferroptosis is an iron-dependent form of regulated cell death triggered by the lethal accumulation of lipid peroxides, and its dysregulation is implicated in cancer development.

Coffee intake reduced gout risk by decreasing urate and urea while increasing SHBG levels in plasma: a mediation Mendelian randomization study.

Objective: This study aims to investigate the causal relationships between specific dietary habits and the risk of gout, while identifying the mediators involved in these associations.

Methods: We initially assessed the causal effects of five dietary habits on gout by two-sample Mendelian randomization (MR). Subsequently, we identified mediators from five plasma metabolites by two-step MR, including urate, urea, sex hormone-binding globulin (SHBG), interleukin-18 (IL-18), and C-reactive protein (CRP).

Targeting O-GlcNAcylation in cancer therapeutic resistance: The sugar Saga continues.

O-linked-N-acetylglucosaminylation (O-GlcNAcylation), a dynamic post-translational modification (PTM), holds profound implications in controlling various cellular processes such as cell signaling, metabolism, and epigenetic regulation that influence cancer progression and therapeutic resistance. From the therapeutic perspective, O-GlcNAc modulates drug efflux, targeting and metabolism. By integrating signals from glucose, lipid, amino acid, and nucleotide metabolic pathways, O-GlcNAc acts as a nutrient sensor and transmits signals to exerts its function on genome stability, epithelial-mesenchymal transition (EMT), cell stemness, cell apoptosis, autophagy, cell cycle.

A Treg-related riskscore model may improve the prognosis evaluation of colorectal cancer.

Background: Colorectal cancer (CRC) poses a significant health challenge. This study aims to investigate the prognostic value of a regulatory T cell (Treg)-related gene signature in CRC.

Methods: We extracted the gene expression and clinical data on CRC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases.

Palmitoylation alters LDHA activity and pancreatic cancer response to chemotherapy.

Lactate dehydrogenase A (LDHA) serves as a key regulator of the Warburg Effect by catalyzing the conversion of pyruvate to lactate in the final step of glycolysis. Both the expression level and enzyme activity of LDHA are upregulated in cancers, however, the underlying mechanism remains incompletely understood. Here, we show that LDHA is post-translationally palmitoylated by ZDHHC9 at cysteine 163, which promotes its enzyme activity, lactate production, and reduces reactive oxygen species (ROS) generation.

Safety and efficacy of immune checkpoint inhibitor rechallenge in advanced non-small cell lung cancer: a retrospective study.

We conducted a retrospective study to evaluate the efficacy of immune checkpoint inhibitor (ICI) rechallenge in patients with advanced non-small cell lung cancer (NSCLC). The study included 111 patients who had previously received ICI therapy and experienced disease progression. The primary endpoints assessed were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).

The efficacy of immune checkpoint inhibitors is limited in elderly NSCLC: a retrospective efficacy study and meta-analysis.

Immune checkpoint inhibitors (ICIs) have improved the long-term survival of NSCLC patients. However, the efficacy of ICIs in elderly NSCLC patients remains controversial. We conducted a retrospective study and meta-analysis exploring the efficacy of ICIs in those patients using public databases and RCTs.

ZDHHC5-mediated NLRP3 palmitoylation promotes NLRP3-NEK7 interaction and inflammasome activation.

The nucleotide-binding domain (NBD), leucine-rich repeat (LRR), and pyrin domain (PYD)-containing protein 3 (NLRP3) inflammasome is a critical mediator of the innate immune response. How NLRP3 responds to stimuli and initiates the assembly of the NLRP3 inflammasome is not fully understood. Here, we found that a cellular metabolite, palmitate, facilitates NLRP3 activation by enhancing its S-palmitoylation, in synergy with lipopolysaccharide stimulation.

Deep-learning-driven dose prediction and verification for stereotactic radiosurgical treatment of isolated brain metastases.

Purpose: While deep learning has shown promise for automated radiotherapy planning, its application to the specific scenario of stereotactic radiosurgery (SRS) for brain metastases using fixed-field intensity modulated radiation therapy (IMRT) on a linear accelerator remains limited. This work aimed to develop and verify a deep learning-guided automated planning protocol tailored for this scenario.

Methods: We collected 70 SRS plans for solitary brain metastases, of which 36 cases were for training and 34 for testing.

High endothelial venules predict response to PD-1 inhibitors combined with anti-angiogenesis therapy in NSCLC.

Tumor-associated high endothelial venules (TA-HEVs) mediate lymphocyte entry into tumors. Therefore, combined anti-angiogenesis therapy and programmed death-1 (PD-1) inhibitors might stimulate tumor immunity. This study will explore the TA-HEVs and real-world data of the combination therapy in non-small cell lung cancer (NSCLC).

Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of YK-029A in Treatment-Naive Patients With Advanced NSCLC Harboring EGFR Exon 20 Insertion Mutations: A Phase 1 Trial.

Introduction: Treatment options for treatment-naive patients with advanced NSCLC harboring EGFR exon 20 insertion (ex20ins) mutations are limited. This study evaluated the safety, tolerability, and pharmacokinetics of YK-029A, a third-generation EGFR tyrosine kinase inhibitor, and the preliminary efficacy of YK-029A in treatment-naive patients with EGFR ex20ins mutation.

Methods: This multicenter, dose-escalation, and dose-expansion phase 1 clinical trial enrolled patients with NSCLC harboring EGFR mutations.