Journal of Cancer最新文献

Objective: Although single-fraction high-dose-rate brachytherapy (SFHDR-BT) for localized prostate cancer has been attempted in clinical trials, there is currently a lack of relevant medical evidence. It is essential to conduct a systematic analysis of the long-term safety and efficacy of SFHDR-BT. Materials and methods: Comprehensive and systematic searches for eligible studies were performed in PubMed, Embase, and the Cochrane Library databases. The primary endpoints included safety and efficacy, represented by toxic effects, biochemical recurrence-free survival (bRFS) and overall survival (OS), respectively. The proportion rates were used as the effect measure for each study and were presented with corresponding 95% confidence intervals (CI). Results: Eight studies met the inclusion criteria for quantitative analysis, including 552 patients. The median follow-up was 71.3 months (60-72.8 months). The estimates of cumulative occurrence for severe gastrointestinal (GI) and genitourinary (GU) toxic effects were 0 and 3% (95% CI 1-5%), respectively. The pooled cumulative incidence of grade ≥ 3 sexual dysfunction occurrence was 4% (95% CI 1-7%). The estimate of long term bRFS was 72% (95% CI 68-76%) and 90% (95% CI 85-95%) for long term OS. Conclusion: In general, SFHDR-BT is well tolerated and associated with suboptimal clinical benefit in patients with localized prostate cancer. High-quality prospective studies of SFHDR-BT are necessary to verify its safety and efficacy.

Background: Intrahepatic cholangiocarcinoma (iCC) is a rare malignant liver tumor with limited therapeutic advancements. Despite its increasing global incidence knowledge of treatment options remains stagnant, leading to poor five-year patient survival rates and high recurrence post-surgery. ALDH1A1, a member of the ALDH superfamily, is associated with cancer stem cells and has conflicting reports regarding its prognostic role in iCC. This retrospective study analyzed 69 iCC patient samples from University Hospital Freiburg. Tissue microarrays (TMAs) were constructed, and ALDH1A1 expression was immunohistochemically assessed using machine learning algorithms. Script-based Survival analysis employed Kaplan-Meier curves, log-rank tests, and Cox Proportional Hazards Models. ALDH1A1 overexpression, both in tumor and stromal cells, correlates with favorable overall survival in iCC. Gender-specific analyses indicate a more pronounced effect in females. These findings suggest ALDH1A1 as a potential prognostic biomarker in iCC, warranting further validation in larger cohorts and exploration as a therapeutic target.

Background: HOXD13, a member of the homeobox gene family, plays a critical role in developmental processes and has been implicated in various malignancies, including pancreatic cancer and glioma. However, its role in oral squamous cell carcinoma (OSCC) remains poorly understood. This study aimed to elucidate the potential of HOXD13 as a diagnostic biomarker and therapeutic target for OSCC. Methods: We conducted a comprehensive analysis of OSCC samples from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA)-head and neck squamous cell carcinoma (HNSCC) databases. Differentially expressed genes (DEGs) with upregulated expression were identified using Venn diagrams. Functional annotation was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A protein-protein interaction (PPI) network was constructed, and 10 key hub genes were identified using the cytoNCA method in Cytoscape. Subsequently, these hub genes were validated using quantitative real-time PCR (qRT-PCR) in tissue samples and cell lines. The impact of HOXD13 knockdown on OSCC cell proliferation and migration was assessed through lentiviral transduction followed by Cell Counting Kit-8 (CCk-8), 5-Ethynyl-2'-deoxyuridine (EdU), wound healing, and Transwell assays. Additionally, proteomic sequencing was performed to explore the effects on lipid metabolism-related pathways. Result: Bioinformatic analysis revealed 121 upregulated DEGs in OSCC. Among these, 10 hub genes (FOXM1, CSF2, FN1, HOXD13, MMP9, SPP1, BIRC5, CXCL11, CXCL9, and FOXA2) were identified using the PPI network and Cytoscape analysis. HOXD13 was notably upregulated in OSCC tissues and cell lines, showing high diagnostic potential with an area under the receiver operating characteristics (ROC) curve (AUC) of 0.9. Immune infiltration analysis indicated significant differences in the tumor microenvironment associated with HOXD13 expression levels. Stable knockdown of HOXD13 in OSCC cell lines resulted in a marked reduction in cell proliferation and migration. Proteomic analysis post-HOXD13 knockdown highlighted alterations in fatty acid degradation pathways and increased expression of related metabolic enzymes. Conclusion: HOXD13 is significantly upregulated in OSCC, and its inhibition reduces OSCC cell proliferation and migration. Additionally, HOXD13 affects fatty acid metabolism in OSCC, suggesting its potential as a therapeutic target and biomarker.

Background: Triggering receptor expressed in myeloid cells-1 (TREM1) is an important regulator of innate and adaptive immunity, which can directly amplify an inflammatory response. Current studies have found the immunomodulatory role of TREM1 in tumor microenvironment. However, the role of TREM1 in ovarian cancer (OV) remains unclear. Methods: Based on TCGA and GEO database, we performed bioinformatics analysis to evaluate the expression profile of TREM1. Then, the prognostic value of TREM1 was determined through Kaplan-Meier survival analyses. GO and KEGG enrichment along with GSEA analyses were performed to identify potential biological functions of TREM1 based on the gene co-expression network. IHC and RT-qPCR on clinical samples were performed to validate our database-derived results. Additionally, ESTIMATE and CIBERSORT analyses were used to assess the correlation between TREM1 and tumor microenvironment. Finally, the expression, prognosis and immune regulation patterns of TREM1 in pan-cancer were further explored to validate the role of TREM1 as a biomarker. Results: The expression of TREM1 is abnormally high in OV than in normal tissues. Patients with high TREM1 expression were linked with poor overall survival (OS) and disease-free survival (DFS). Then, cox regression analysis and a nomogram indicated that TREM1 was an independent prognostic factor and proved the effective predictive performance in OV. Enrichment analysis showed that TREM1 was highly enriched in cancer-and immune-related pathways. Additionally, immune analysis revealed that TREM1 was robustly positively associated with tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) infiltrating. Moreover, pan-cancer analysis showed TREM1 was closely associated with prognosis and immune-related genes expression in various types of cancer. Conclusions: Through a systematic and comprehensive analysis, our study revealed that TREM1 could serve as a prognostic and immunological biomarker in ovarian cancer.

Background: Endometrial cancer (UCEC) has a significant detrimental effect on patient quality of life. Although pyroptosis-related genes have been reported to contribute to tumor pathogenesis, the specific mechanism of pyroptosis in patients with UCEC remains elusive. Methods: We provide an overview of the landscape of pyroptosis-related genes in UCEC tissues through single-cell RNA sequencing (scRNA-Seq) datasets from the tissues of UCEC of 6089 cells. In addition, pyroptosis-related gene expression pattern was verified based on the RNA-Seq datasets, and observation of abnormal pathological characteristics of UCEC tissue. Results: The pyroptosis-related gene IL-6 is specifically upregulated in epithelial cells and dysregulates cell population proliferation and enhances apoptosis. The upregulation of BAX and TNF expression in macrophages induces infiltration of aberrantly activated macrophages, which display dysfunctional differentiation in tumor tissues, altered immune responses, and activation of the tumor necrosis factor (TNF) pathway in UCEC macrophages. In addition, dysregulation of pyroptosis-related genes induces aberrant cell-cell communication in tumor tissues and mediates ligand-receptor interactions between various cell types in UCEC via the TNF signaling pathway to promote cancer progression. Quantitative real-time (PCR) and immunohistochemistry were used for the in vitro experimental validation. Conclusion: Pyroptosis-related genes can serve as biomarkers for UCEC, playing a role in early disease diagnosis, helping to predict patient prognosis, and guiding the selection of personalized treatment options.

Band selection is a common approach to reduce the data dimensionality of hyperspectral imagery. It extracts several bands of importance in some sense by taking advantage of high spectral correlation. In medical imaging, narrow-band imaging (NBI) is an imaging technique for endoscopic diagnostic medical tests, where light of specific blue and green wavelengths is used to enhance the detail of certain aspects of the surface of the mucosa. A special filter is electronically activated by a switch in the endoscope leading to the use of ambient light of wavelengths of 415 nm (blue) and 540 nm (green). Because the peak light absorption of hemoglobin occurs at these wavelengths, blood vessels will appear very dark, allowing for their improved visibility and in the improved identification of other surface structures. NBI when compared with the white-light imaging (WLI) have proven to have better precision when combined with computer-aided diagnosis (CAD, Intespec C, Hitspectra Intelligent Technology Co., Kaohsiung, Taiwan) in detecting cancerous images. NBI endoscopes are specialized equipment that may not be widely available in all healthcare settings. By leveraging existing WLI endoscopic systems and developing algorithms to simulate NBI imaging, healthcare facilities can achieve similar di-agnostic capabilities without the need for additional costly equipment. Therefore, in this study, algorithm known as the SAVE (spectrum-aided visual enhancer) has been developed which can simulate NBI from the WLI images through an intelligent band-selective hyperspectral imaging for Olympus endoscope. The results suggested that the SAVE-NBI images had a better precision and F1-score than the WLI images.

Background: Longikaurin A (LK-A), a naturally occurring ent-kaurane diterpenoid, has been identified as a promising anti-cancer agent. This study aims to elucidate the anti-tumorigenic effects of LK-A on oral squamous cell carcinoma (OSCC) cells and to unravel its underlying mechanisms. Methods: In vitro assays, including CCK-8 and EdU, were performed to assess cell viability and proliferation. Transwell migration and invasion assays evaluated cell mobility and invasive potential. Apoptotic effects were analyzed using Annexin V-FITC/PI staining and TUNEL assays. Western blot analysis was conducted to examine protein expression related to cell cycle, apoptosis, and the PI3K/Akt signaling pathway. In vivo experiments involved treating mouse xenograft models with LK-A and evaluating tumor growth and signaling pathway inhibition through immunohistochemistry and Western blot assays. Results: LK-A significantly suppressed cell viability and proliferation in a dose-dependent manner, with IC50 values of 4.36 μM and 4.93 μM at 24 h, and 1.98 μM and 2.89 μM at 48 h for CAL27 and TCA-8113 cells, respectively. EdU assays revealed a reduction in the EdU positive rate, and cell cycle analysis showed G2/M phase arrest. Western blot analysis confirmed decreased expression of CyclinB1 and Cdc2. LK-A significantly inhibited OSCC cell mobility and invasive potential, with downregulation of MMP-2 and MMP-9 expression. Apoptotic effects were confirmed by increased apoptosis, upregulation of Bax and cleaved caspase-3, and downregulation of Bcl-2. LK-A suppressed the PI3K/AKT signaling pathway, as evidenced by reduced phosphorylation of PI3K, AKT, and mTOR. The AKT activator SC79 reversed the antiproliferative and pro-apoptotic effects of LK-A. In vivo, LK-A significantly inhibited tumor growth in mouse xenograft models, with reduced tumor weights and volumes, and no significant loss in body weight. Immunohistochemistry and Western blot assays confirmed the inhibition of p-Akt and Ki-67 expression. Conclusion: These findings suggest that LK-A exerts potent antiproliferative, anti-migratory, and pro-apoptotic effects on OSCC cells through the suppression of the PI3K/AKT signaling pathway, demonstrating its potential as a therapeutic agent for OSCC.

Background: The lymph node ratio (LNR), involved nodes/ lymph nodes examined, is associated with survival in colon cancer. Previous studies investigated the prognostic role of LNR regardless of TNM N staging or compared LNR and TNM N stages for prognostic strength. However, LNR may be utilized to obtain additional prognostic information rather than replacing TNM staging in daily practice. This study aimed to evaluate the role of LNR in TNM N stages to provide further prognostic information in daily practice. Methods: Patients with stage-III colon cancer who underwent surgery and adjuvant chemotherapy were included. pN1c tumors (tumor deposits without node involvement) and rectal cancers were excluded. Clinicopathological parameters and LNR in pN1a-b and pN2 groups were evaluated for recurrence-free survival (RFS). Results: A total of 97 patients were included [pN1a-b: n=69 (71.1%) and pN2: n=28 (28.9%)]. Median LNR in the entire population was 0.09 (0.01-0.84) with a median lymph node examined of 22 (8-89) and involved of 2 (1-17). Median RFS was not reached in the pN1a-b and pN2 groups during a median follow-up of 20.8 months (1.13-101.03), with significantly better survival of the pN1a-b group (p=0.003). Among the pN1a-b group, the LNR cut-off was set as 0.10. LNR significantly discriminated RFS (Median not-reached, p=0.001). Among the pN2 group, the LNR cut-off was set as 0.25 and LNR significantly discriminated RFS [Not reached vs. 11.40 months (95%CI: 3.57-16.83), p=0.004]. Combined pN-LNR groups revealed significant discrimination in RFS (p<0.001). RFS was not statistically different between pN2-LNR≤0.25 and pN1-LNR>0.10 groups (p=0.282). In multivariable analysis with clinicopathological parameters, only LNR was significant (p=0.023), whereas the pN stage did not remain significant (p=0.637). Conclusion: LNR adds further prognostication in pN1a-b and N2 groups. LNR may be utilized to detect patient subgroups in different TNM N sages (pN1a-b and pN2) but with similar prognoses. This further prognostic information may assist clinical decisions in practice. The results of this study emphasize an adequate and higher number of lymph node samples in surgery.

Objective: Hesperidin, an active constituent of traditional Chinese medicine, Chenpi, exhibits anticancer properties across different cancers. This study aimed to clarify the efficacy of Hesperidin against tumors and its mechanisms of action in colon cancer. Method: We assessed the efficacy of Hesperidin on human colon cancer cells (HCT-116 and DLD-1) and normal colonic epithelial cells (NCM460). We quantified cell viability at various Hesperidin concentrations using the CCK8 assay in a series of experiments. We employed clone formation, EdU incorporation, Transwell, and wound healing assays to clarify Hesperidin efficacy on cancer cell proliferation, invasion, and migration. Western blot analyses revealed modulations in epithelial-mesenchymal transition-related proteins, SLC5A1, EGFR, and phosphorylated EGFR levels following Hesperidin exposure. Co-IP assays further validated the interaction between SLC5A1 and EGFR. Our findings were significantly restored following SLC5A1 overexpression in colon cancer cells, highlighting its pivotal role in Hesperidin-induced responses. Results: Hesperidin selectively impaired the viability of HCT-116 and DLD-1 colon cancer cells at specific concentrations while preserving normal NCM460 cells. This flavonoid dose-dependently reduced cancer cell proliferation, migration, and invasion. It significantly suppressed SLC5A1 and phosphorylated EGFR expression. We identified a direct SLC5A1-EGFR interaction essential for regulating EGFR activity in colon cancer. Overexpressing SLC5A1 significantly reduced the inhibitory effects of Hesperidin, highlighting its crucial role in this context. Conclusion: Hesperidin exerts its anticancer effects on colon cancer by inhibiting SLC5A1 expression and consequently downregulating EGFR phosphorylation.

Background: Glioblastoma multiforme (GBM) is the most lethal type of primary brain tumor, necessitating the discovery of reliable serum prognostic biomarkers. This study aimed to investigate the prognostic value of serum Interleukin-6 (IL-6) in GBM patients. Methods: Bioinformatics analysis via gene set enrichment analysis was conducted on The Cancer Genome Atlas RNA-seq data to explore the pathways enriched in samples with high IL-6 expression. The Tumor IMmune Estimation Resource database was used to analyze the association between IL-6 expression and immune cell infiltration. To validate the role of IL-6 in a clinical setting, a retrospective cohort study was conducted on newly diagnosed GBM patients. Serum IL-6 levels were repeatedly measured at key milestone time points, and their correlation with survival data was analyzed. Results: Bioinformatics analysis revealed that high IL-6 expression is associated with the activation of procancer pathways, that there is a positive correlation between IL-6 expression and immune cell infiltration in GBM. Between March 2021 and September 2023, 36 GBM patients and their serum IL-6 measurements at various time points were included in the clinical data analyses. Elevated serum IL-6 levels at baseline, with a cutoff of 7pg/mL, were identified in 11 patients (30.6%). In the multivariate analyses for overall survival (OS), elevated IL-6 was a significant risk factor (p = 0.048), along with unfavorable surgical resection (p = 0.039) and O6-methylguanine-DNA methyltransferase promotor unmethylation (p = 0.027). The median actuarial OS of the high initial IL-6 group was significantly shorter than that of the low initial IL-6 group (6.4 vs. 19.7 months, p < 0.001). However, IL-6 levels at other time points were not related to patient prognosis. Conclusion: Elevated IL-6 mRNA expression is correlated with the activation of procancer pathways, increased immune cell infiltration, and poor prognosis in GBM patients. In addition, elevated serum IL-6 at baseline is a negative prognostic factor confirmed in a clinical study. Serum IL-6 may be a potential prognostic biomarker enhancing the management of GBM.