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Background: Colorectal cancer (CRC) is a leading cause of cancer-related deaths globally. The heterogeneity of the tumor microenvironment significantly influences patient prognosis, while the diversity of tumor cells shapes its unique characteristics. A comprehensive analysis of the molecular profile of tumor cells is crucial for identifying novel molecular targets for drug sensitivity analysis and for uncovering the pathophysiological mechanisms underlying CRC.
Methods: We utilized single-cell RNA sequencing technology to analyze 13 tissue samples from 4 CRC patients, identifying key cell types within the tumor microenvironment. Intercellular communication was assessed using CellChat, and a risk score model was developed based on eight prognostic genes to enhance patient stratification for immunotherapeutic approaches. Additionally, experiments were performed on , a gene strongly associated with poor prognosis, to validate its potential role as a therapeutic target in CRC progression.
Results: Eight major cell types were identified across the tissue samples. Within the tumor cell population, seven distinct subtypes were recognized, with the C0 + tumor cells subtype being significantly linked to cancer progression and poor prognosis. CellChat analysis indicated extensive communication among tumor cells, fibroblasts, and immune cells, underscoring the complexity of the tumor microenvironment. The risk score model demonstrated high accuracy in predicting 1-, 3-, and 5-year survival rates in CRC patients. Enrichment analysis revealed that the C0 + tumor cell subtype exhibited increased energy metabolism, protein synthesis, and oxidative phosphorylation, contributing to its aggressive behavior. experiments confirmed as a critical gene associated with poor prognosis, suggesting its viability as a target for improving drug sensitivity.
Conclusion: In summary, this study advances our understanding of CRC progression by identifying critical tumor subtypes, molecular pathways, and prognostic markers that can inform innovative strategies for predicting and enhancing drug sensitivity. These findings hold promise for optimizing immunotherapeutic approaches and developing new targeted therapies, ultimately aiming to improve patient outcomes in CRC.
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http://dx.doi.org/10.3389/fimmu.2024.1509658 | DOI Listing |
Nucleic Acids Res
December 2024
Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, Jilin 130022, P. R. China.
G-quadruplexes (G4s), as an important type of non-canonical nucleic acid structure, have received much attention because of their regulations of various biological processes in cells. Identifying G4s-protein interactions is essential for understanding G4s-related biology. However, current strategies for exploring G4 binding proteins (G4BPs) include pull-down assays in cell lysates or photoaffinity labeling, which are lack of sufficient spatial specificity at the subcellular level.
View Article and Find Full Text PDFSensitive detection of incident acoustic waves over a broad frequency band offers a faithful representation of photoacoustic pressure transients of biological microstructures. Here, we propose a plasmon waveguide resonance sensor for responding to the photoacoustic impulses. By sequentially depositing Au, MgF, and SiO films on a coverslip, a composite waveguide layer produces a tightly confined optical evanescent field at the SiO-water interface with extremely strong electric field intensity, enabling the retrieval of photoacoustic signals with an estimated noise-equivalent-pressure (NEP) sensitivity of ∼92 Pa and a -6-dB bandwidth of ∼208 MHz.
View Article and Find Full Text PDFJ Clin Invest
December 2024
Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy.
PARP inhibitors (PARPi) have received regulatory approval for the treatment of several tumors, including prostate cancer (PCa), and demonstrate remarkable results in the treatment of castration-resistant prostate cancer (CRPC) patients characterized by defects in homologous recombination repair (HRR) genes. Preclinical studies showed that DNA repair genes (DRG) other than HRR genes may have therapeutic value in the context of PARPi. To this end, we performed multiple CRISPR/Cas9 screens in PCa cell lines using a custom sgRNA library targeting DRG combined with PARPi treatment.
View Article and Find Full Text PDFJ Clin Invest
December 2024
Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America.
KRAS is the most frequently mutated oncogene in lung adenocarcinoma, with G12C and G12V being the most predominant forms. Recent breakthroughs in KRASG12C inhibitors have transformed the clinical management of patients with G12C mutation and advanced our understanding of its function. However, little is known about the targeted disruption of KRASG12V, partly due to a lack of specific inhibitors.
View Article and Find Full Text PDFCell Oncol (Dordr)
December 2024
Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410013, China.
Purpose: Our study aims to develop and validate a novel molecular marker for the prognosis and diagnosis of hepatocellular carcinoma (HCC) MATERIALS & METHODS: We retrospectively analyzed mRNA expression profile and clinicopathological data of HCC patients fetched from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and The International Cancer Genome Consortium (ICGC) datasets. Univariate Cox regression analysis was performed to collect differentially expressed mRNA (DEmRNAs) from HCC and non-tumor tissues, and YEATS2, a prognostic marker, was identified by further analysis. ROC curve, survival analysis and multivariate Cox regression analysis as well as nomograms were used to evaluate the prognosis of this gene.
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