Journal of Cancer最新文献

Although the impact of circulating metabolites on the immune microenvironment of lung cancer has been recognized, the causal relationship between these metabolites and non-small cell lung cancer (NSCLC) remains unclear. We investigated whether 233 metabolic traits have a causal effect on NSCLC using data from population-based genome-wide association studies (GWAS). We employed the inverse variance weighted (IVW) method with random effects as the primary analytical tool. After performing two-sample Mendelian randomization (MR) analysis of 233 metabolic traits on NSCLC risk, we selected the significant ones for further sensitivity analyses. Applying a false discovery rate (FDR) correction (P_FDR < 0.05), we identified a causal relationship between two metabolic traits and NSCLC: the ratio of Omega-3 fatty acids to total fatty acids (Omega_3_pct) (OR: 1.18, 95% CI: 1.08-1.29, P_FDR=0.036) and the ratio of 22:6 docosahexaenoic acid to total fatty acids (DHA_pct) (OR: 1.26, 95% CI: 1.11-1.42, P_FDR=0.036). Sensitivity analyses yielded consistent results. We innovatively utilized GWAS data for multiple metabolic traits to conduct a two-sample Mendelian randomization analysis of the association between 233 metabolic traits and NSCLC. The findings suggest that higher proportions of Omega-3 fatty acids and 22:6 docosahexaenoic acid in total fatty acids may causally increase the risk of NSCLC, providing novel insights into the role of circulating metabolites in lung cancer development.

Background: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer characterized by a low incidence but a poor prognosis. The purpose of the study was to develop a clinical prediction model utilizing non-invasive blood markers to effectively evaluate the prognosis of cHCC-CCA patients following hepatic resection. Methods: The retrospective analysis was conducted on 125 patients with cHCC-CCA who underwent hepatic resection between April 2013 and October 2022. All cHCC-CCA patients were randomly assigned to the training group (n = 63) and the validation group (n =62). A nomogram based on patient clinical factors was established using cox regression analysis. Receiver operating characteristic curves (ROCs) were used to assess the predictive performance of the model. Calibration and decision curves were employed to evaluate the model's prediction accuracy and goodness of fit. Results: Multivariate analysis revealed significant associations between lymphatic metastasis, microvascular invasion (MVI), gamma-glutamyl transpeptidase to albumin ratio (GAR), carcinoembryonic antigen (CEA), prothrombin time (PT), alpha-fetoprotein (AFP), hepatitis B virus (HBV), and overall survival. Based on these prognostic factors, a nomogram model was established and validated using the validation set. Calibration curves demonstrated good consistency in the 1-year, 3-year, and 5-year survival rates of patients. Additionally, the ROC analysis indicated the model's strong predictive ability, and the decision curves confirmed its clinical applicability. Conclusion: This study successfully developed a nomogram model for predicting survival outcomes in patients with cHCC-CCA following hepatectomy.

Medicinal plants play a critical role in drug development, serving as a valuable source of bioactive compounds. Cancer, characterized by uncontrolled cell proliferation, presents significant challenges in treatment due to its multifaceted nature. This study aims to evaluate the anticancer potentials of selected medicinal plants specifically focusing on in vitro and in vivo studies that evaluate therapeutic implications for cancer treatment. A systematic review was conducted to assess both in vitro and in vivo studies involving selected medicinal plants: Saussurea costus, Lepidium sativum, Rhus tripartite, Pyrus communis, Chenopodium murale, Erucaria hispanica, Trigonella hamosa, Argemone ochroleuca, and Galium odoratum. The review involved analyzing cancer cell lines, plant parts used, extraction methods, and mechanisms of action reported in the literature. A total of sixty-nine articles were identified that investigated the anticancer properties of the selected plants. Notably, S. costus, L. sativum, and R. tripartite exhibited significant anticancer potential. In contrast, P. communis, C. murale, E. hispanica, T. hamosa, A. ochroleuca, and G.odoratum had limited studies available. The predominant mechanism of action identified for the anticancer activity was the induction of apoptosis. The findings indicate that these medicinal herbs possess promising therapeutic potential as anti-cancer agents. However, further research is warranted for P. communis, C. murale, E. hispanica, T. hamosa, A. ochroleuca, and G. odoratum to enhance understanding of their anticancer activities and explore their full therapeutic capabilities.

NCAPH is mainly involved in the transformation of nuclear chromatin in the intercellular phase into a highly heliform nuclear chromosome, encoded by a gene on chromosome 2q11.2. Studies have found that NCAPH, as an oncogene, plays important roles in the occurrence and development of several cancers, significantly affecting the survival and prognosis of patients. However, the role of NCAPH in low-grade glioma (LGG) has been largely unexplored. Here, we conduct a comprehensive analysis of NCAPH expression, abundance of cell subsets in single-cell cohorts, prognosis, co-localization, epigenetic alterations, functional enrichment, tumor immune-related features, immunotherapy response, drug sensitivity, and molecular docking in LGG. Our findings suggest that NCAPH is significantly overexpressed in LGG and is strongly relevant to poor prognosis, and that NCAPH plays important roles in reshaping the tumor microenvironment, which may promote immune tolerance of LGG and thus become a potential immunotherapeutic target. The sensitivity of LGG patients with high NCAPH expression to chemotherapy agents such as temozolomide also suggests the potential therapeutic effect of chemotherapy combined with immunotherapy. Furthermore, NCAPH was positively correlated with cell cycle, proliferation, DNA damage and repair, EMT, invasion, and apoptosis, while negatively associated with inflammation, quiescence and angiogenesis. Together, this study provides a comprehensive understanding of the role of NCAPH in LGG and suggests that NCAPH may be a potential prognostic biomarker for LGG patients, with potential for drug development and immunotherapy.

Colorectal cancer (CRC) is one of the most common malignant tumors. Isoliquiritigenin (ISL), a natural chalcone compound extracted from the roots of licorice and other plants, has demonstrated significant anti-tumor activity in various cancers. However, its specific mechanisms of action against CRC remain unclear. In this study, we investigated the molecular mechanisms underlying the effects of ISL targeting Fibroblast Growth Factor Receptor 4 (FGFR4) in CRC. Our findings revealed that FGFR4 is highly expressed in CRC cell lines, and functional assays demonstrated that silencing FGFR4 significantly inhibits cellular proliferation and migration. Further mechanistic studies showed that FGFR4 regulates fatty acid biosynthesis and the PI3K/Akt signaling pathway, as evidenced by the downregulation of Fatty Acid Synthase (FASN) and PI3K/Akt pathway proteins upon FGFR4 knockdown. Moreover, ISL significantly suppresses CRC cell proliferation and migration while disrupting tumor cell fatty acid metabolism. This study suggests that ISL may inhibit CRC progression by downregulating FGFR4 and suppressing PI3K/Akt-mediated fatty acid metabolism reprogramming.

Epigenetic regulation, encompassing DNA methylation, histone modifications, and non-coding RNA activities, is a crucial mechanism through which gene expression is modified without corresponding changes in genomic DNA sequences. Dysregulation of these mechanisms can lead to histone and DNA modifications that either suppress or enhance the expression of disease progression-related genes. Among these regulatory processes, histone modifications are particularly significant, as they contribute to genomic stability, DNA repair, and chromatin dynamics, all of which influence breast cancer initiation and progression. This review offers a detailed analysis of the current state of research centered on epigenetic regulatory factors, with a particular focus on the role that histone modifications play in the treatment of breast cancer. It also examines the interplay between epigenetic modifications and the effectiveness of radiotherapy and chemotherapy when treating breast cancer. Lastly, this article explores the potential of epigenetic regulatory factors as viable targets for the future design of new anticancer therapies.

Background: Bone-predominant metastatic renal cell carcinoma (mRCC) presents significant clinical challenges due to its associated morbidities and poor prognosis. Optimal first-line treatment remains unclear, largely because these patients are often excluded from clinical trials due to difficulties in measuring bone lesions. Emerging evidence suggests that bone metastases exhibit high angiogenesis gene signatures, potentially predicting favorable responses to tyrosine kinase inhibitors (TKIs). Methods: We conducted a multicenter retrospective analysis of patients with bone-predominant mRCC treated at The Ohio State University Comprehensive Cancer Center and Fred Hutchinson Cancer Center from January 2008 to June 2021. Bone predominance was defined as having a greater number of osseous metastases compared to extra-osseous sites using computed tomography or bone scans. Patients receiving first-line TKIs or immune checkpoint inhibitors (ICIs) were included; those treated with combination TKI-ICI therapies were excluded due to limited numbers. Demographic, clinical, and treatment data were collected. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier methods and compared using the log-rank test. Univariate Cox regression analysis was conducted to identify factors associated with OS. Results: A total of 69 patients with bone-predominant mRCC were identified, with 40 receiving TKIs and 29 receiving ICIs as first-line therapy. Baseline characteristics were comparable between groups. The median OS was significantly longer for patients treated with TKIs compared to those receiving ICIs (41.3 months vs. 19.3 months; log-rank P = 0.036). A trend toward improved median PFS was observed in the TKI group (7.9 months vs. 4.9 months; P = 0.075). Univariate analysis showed that treatment with ICIs was associated with an increased risk of death compared to TKIs (hazard ratio = 1.96; P = 0.040). Objective response rates were higher in the TKI group (22.9% vs. 12.0%), although this difference was not statistically significant (P = 0.332). Conclusions: In this multicenter real-world analysis, first-line treatment with TKIs was associated with significantly improved OS compared to ICIs in patients with bone-predominant mRCC. These findings suggest that TKI-containing regimens may be the preferred front-line therapy for this patient subgroup. Prospective studies are warranted to validate these results and to optimize treatment strategies for bone-predominant mRCC.

Background: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality. Given its established associations with gut microbiota and inflammatory bowel disease (IBD), elucidating their relationships and developing predictive models are critical for early detection and therapy. Methods: Using Mendelian randomization (MR), we integrated data from the MiBioGen Consortium and multiple genome-wide association studies (GWAS). Single nucleotide polymorphisms (SNPs) associated with gut microbiota were mapped to genes, followed by gene selection via least absolute shrinkage and selection operator (LASSO) regression. Transcriptome analyses identified differential gene expressions and immune cell infiltration patterns. Six machine learning models were integrated through soft voting to predict CRC risk, validated by single-cell sequencing analysis. Results: Mediation MR identified 12 gut microbial taxa causally associated with CRC, mediated partially by IBD. SNP mapping and expression analysis highlighted eight CRC-associated genes, five of which (FAM120A, GBE1, MCM6, MSRA, ZDHHC4) were further underscored by drug target MR and summary-data-based MR (SMR). Transcriptomics implicated dysregulation in the neuroactive ligand-receptor interactions and the G2/M DNA checkpoint pathway. Immune infiltration analysis demonstrated elevated CD4⁺ T cells and M0 macrophages in the high-LASSO score group. Integrated machine learning models built using the five key genes achieved robust predictive performance. Single-cell sequencing analysis confirmed gene expression patterns. Conclusion: By integrating mediation MR, transcriptomics, and machine learning, this study demonstrated causal relationships between specific gut microbiota and CRC, with IBD as a mediator. We identified potential therapeutic targets and developed robust predictive models, providing crucial insights into the pathogenesis and clinical detection of CRC.

Purpose: With the continuous improvement in the efficacy of neoadjuvant therapy (NAT), a significant proportion of breast cancer patients initially diagnosed with pathologically confirmed axillary lymph node metastasis (pN+) may achieve ypN0 status (no residual nodal metastasis) following NAT. This study aims to develop a predictive model for estimating the probability of achieving ypN0 status after NAT, thereby assisting surgeons in making optimal decisions regarding axillary management strategies. Methods: This retrospective study enrolled 671 patients diagnosed with pN+ at Tianjin Medical University Cancer Institute and Hospital between December 2018 and December 2022, all of whom completed NAT followed by surgical intervention. The cohort comprised 428 HER2-positive and 243 TNBC patients. Clinicopathological and ultrasound imaging data were systematically collected. Patients were stratified into training and validation sets at a 7:3 ratio based on admission dates. Univariate analysis was initially performed on the training set to identify potential factors associated with achieving ypN0 status post-NAT. Variables demonstrating statistical significance were subsequently incorporated into a multivariate logistic regression analysis to determine independent predictors. A predictive nomogram was then constructed using these independent factors via R software for visual interpretation of ypN0 probability. The predictive performance of the model was ultimately evaluated by generating receiver operating characteristic (ROC) curves to assess discriminative ability and calibration curves to quantify prediction accuracy, with further validation performed using the independent validation cohort. Results: In HER2 positive breast cancer patients, those exhibiting histological grade III, HER2 IHC 3+ expression, absence of lymphovascular invasion, clinical N1 stage, prominent and hypervascular tumor CDFI signal pre-NAT, and achievement of breast pathological complete response (bpCR) following NAT were significantly more likely to achieve ypN0 status. Conversely, among TNBC patients, independent predictors of post-NAT ypN0 achievement included histological grade III, taxane-platinum combination regimens, bpCR, dot-linear signals in axillary lymph nodes on post-NAT ultrasound, and minimal transverse diameter of node on final post-NAT ultrasound evaluation. Conclusions: This study established distinct predictive models for HER2-positive and TNBC cohorts with initial pN+ status to estimate the probability of achieving ypN0 following NAT. Both models demonstrated robust predictive performance through rigorous validation, providing clinicians with quantitative tools to optimize axillary management strategies and facilitate precision-based individualized treatment planning.

Breast cancer, including triple-negative breast cancer (TNBC), is the most commonly diagnosed cancer in women, with subtypes differing in treatment options and prognoses. In particular, TNBC, characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression, is the most aggressive subtype, with limited treatment options, high metastatic rates, and poor survival outcomes. In recent years, epigenetic studies have emerged as a promising tool for analyzing gene expression and alterations in TNBC, providing potential insights into the development of novel therapeutic strategies. Epigenetic mechanisms, such as DNA methylation, histone modifications, and non-coding RNA (ncRNA)-mediated gene silencing, play a crucial role in the development and progression of TNBC. Research into these mechanisms holds significant promise for the development of personalized therapeutic approaches, potentially improving outcomes for TNBC patients. This review provides a comprehensive overview of recent advances in research on epigenetic alterations in TNBC, with an emphasis on potential clinical applications aimed at improving survival and quality of life in TNBC patients.