Journal of Cancer最新文献

Background: Skin cutaneous melanoma (SKCM) is a malignant tumor characterized by aggressive invasion and a high tendency for metastasis. This study explores the potential of MCM4 as a biomarker for SKCM and its impact on the tumor microenvironment (TME). Method: A comprehensive analysis of MCM4 was conducted using public databases to characterize the expression, genomic alterations, and clinical significance of MCM4 in pan-cancer, including SKCM. Bioinformatics tools were employed to identify upstream regulators of MCM4. The functional mechanisms of MCM4 in SKCM were explored through correlation, differential, and enrichment analyses. Immune infiltration and drug sensitivity were assessed to understand the role of MCM4 in the TME and its potential therapeutic implications. Functional experiments were performed in A375 and SK-MEL-28 cells. Results: MCM4 were significantly upregulated in tumors. Survival curves indicated that patients with high MCM4 expression had poor survival advantage. SRF was identified as a potential transcription factor regulating MCM4. Functional enrichment revealed a positive correlation between MCM4 and cell cycle-related pathways, and a negative correlation with immune effector process-related pathways. High MCM4 expression was associated with "cold" tumor characteristics. Immunotherapy response analysis demonstrated higher response rates in patients with low MCM4 expression. Drug sensitivity analysis suggested potential therapeutic drug options based on MCM4 expression. Functional experiments confirmed the oncogenesis effects of MCM4 in SKCM cells. Conclusion: MCM4 is a potential prognostic biomarker and predictor of immunotherapy response in SKCM patients.

Due to the poor prognosis and lack of effective therapy options, treating metastatic osteosarcoma (OS), particularly lung metastasis, presents significant therapeutic challenges. It has been shown that both non-coding RNAs (ncRNAs) and protein-coding mRNAs serve as essential for controlling the progression of tumors. Uncertainty persists regarding the whole expression profile and the network of regulation involving competing endogenous RNAs (ceRNAs) between mRNAs and ncRNAs in the OS lung metastasis. To fully understand variations in the expression of lncRNAs, circRNAs, miRNAs, and mRNAs, we introduced whole transcriptome sequencing (RNA-seq) in the three matched primary and lung-metastasis OS tissues used in the current study. Analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology (GO) was carried out for mRNAs exhibiting notably distinct expression patterns. After that, the official RNA hybrid and TargetScan databases were utilized to anticipate and establish the ceRNA networks, which are made up of lncRNAs, circRNAs, miRNAs, and mRNAs. Furthermore, two created ceRNA regulatory pathways, lncRNA PCAT1/miR-370-3p/LRAT, and circ_0012586/miR-200b-5p/MFAP5, were chosen at random and verified using a variety of cell and molecular biology experiments. Ultimately, our research may reveal novel avenues for the prevention or treatment of OS lung metastasis as well as fresh evidence for the underlying mechanism.

Oral cancer is the sixth leading cause of cancer-related mortality worldwide. Recent studies suggest that long non-coding RNAs (lncRNAs) HOXA transcript at the distal Tip (HOTTIP) may influence oral cancer cell growth and invasion, but comprehensive genetic association studies evaluating the impact of HOTTIP single-nucleotide polymorphisms (SNPs) on oral cancer susceptibility, and clinicopathological features are lacking. In this study, we investigated the associations between SNPs in the HOTTIP gene and both oral cancer susceptibility and clinicopathological characteristics. A total of 1,192 controls and 1,205 oral cancer patients were genotyped for four HOTTIP SNPs-rs3807598, rs17501292, rs2067087, and rs1859168-using real-time polymerase chain reaction (PCR). Our results showed that among oral cancer patients aged 60 years or older, those carrying the HOTTIP rs3807598 "GC+CC" genotype had a significantly reduced risk of developing advanced clinical stage and lymph node metastasis. Additionally, carriers of the rs2067087 "CG+GG" polymorphic variants were associated with a lower risk of developing advanced clinical stages. In conclusion, our findings suggest that the HOTTIP rs3807598 and rs2067087 polymorphisms may serve as pivotal predictor for assessing oral cancer progression.

Background: Colorectal cancer (CRC) is the third most common cancer worldwide. In Saudi Arabia, the 2020 cancer incidence report found that CRC was the most common cancer among men and had the highest mortality rate. Given the correlation between cancer symptom awareness and early detection and recognizing the significance of patient history in CRC diagnosis, this study aims to identify the presenting symptoms of CRC, assess survival by stage across the population, and better understand disease demographics in Saudi Arabia. Methods: We conducted a retrospective cohort analysis of 655 patients with CRC diagnosed between 2016 and 2020, inclusive. The cancer registry database at King Khalid University Hospital was used to retrospectively collect data from electronic records. Various relevant data were extracted and analyzed. Results: The results showed that the most common presenting symptom was abdominal pain (329, 50.2%), followed by weight loss (262, 40%), hematochezia (rectal bleeding or blood in stool) (242, 36.9%), and anemia (238, 36.3%). The overall three-year survival rate was 77.6%. For stages I, II, III, and IV it was 100%, 91.9%, 86.4%, and 61.8%, respectively. with a significant difference (p = 0.0001). Conclusions: Rectal bleeding and other "alarming symptoms" were observed in fewer than 40% of the studied population. In the cohort, only one patient was diagnosed via a screening colonoscopy. Study also confirmed that survival improved with earlier stages at diagnosis. Encouraging preventative measures, raising awareness of CRC, and improving access to screening, could all contribute to earlier identification, reduced staging, and a better prognosis.

Metformin may help prevent the development of colorectal cancer (CRC); however, the mechanisms involved remain unclear. This study aimed to investigate the effects of metformin on CRC onset and progression in a mouse model by evaluating any changes to the intestinal mucosal barrier. Sixty BALB/C female mice were randomly divided into control, model, and low-, medium-, and high-dose treatment groups. The CRC models were induced by azoxymethane combined with dextran sulfate sodium. At the time of induction, metformin 125 mg/kg · d, 250 mg/kg · d, and 500 mg/kg · d doses were administered to the low-, medium-, and high-dose groups, respectively. After 14 weeks, no tumor was observed in the control group, and multiple tumors were observed in the four test groups. Fewer tumors emerged in the metformin groups than in the model group. The tumors in the metformin groups were smaller than those in the model group. The expression of ZO-1 and occludin in the colon tissue of mice improved after metformin intervention. We performed intervention studies with varying doses of metformin and a composite disease model (parallel induction of intestinal barrier damage and tumorigenesis) in our experimental design, allowing for novel insights into the temporal effects of metformin. Metformin can improve intestinal mucosal barrier function by restoring the expression of intestinal tight junction proteins in mice and thus may help protect against CRC within a certain dose range.

Chemerin is a protein, encoded by the RARRES2 gene, which has important roles in immune regulation, inflammation and metabolic regulation. Chemerin can affect the proliferation, migration and invasion ability of tumor cells and is important in the occurrence, development, metastasis, differentiation and development of tumors. CMKLR1, GPR1, and CCRL2, the primary cellular receptors for chemerin, can be found in both normal and tumor tissues. Chemerin binds to its receptors to influence tumor growth and metastasis by regulating the inflammatory response and tumor microenvironment. In this paper, the mechanism of chemerin and its receptors in the tumor microenvironment was summarized, providing theoretical basis for further study of the mechanism of chemerin in tumors and for molecular targeted therapy based on chemerin.

Prostate cancer is a prevalent malignancy among men, characterized by complex mechanisms underlying metastasis and treatment resistance. Epigenetic modifications play a crucial role in regulating prostate cancer progression, particularly involving histone methyltransferases such as SET-domain containing 2 (SETD2) and Enhancer of Zeste homolog 2 (EZH2). SETD2 contributes to chromatin stability by catalyzing the trimethylation of histone H3 lysine 36 (H3K36me3), and its downregulation is strongly correlated with increased invasiveness and epithelial-mesenchymal transition in prostate cancer. Conversely, EZH2, the catalytic subunit of Polycomb Repressive Complex 2, mediates gene silencing through H3K27me3 modification and is frequently overexpressed in advanced disease, promoting tumor metastasis and resistance to therapy. Notably, SETD2 regulates EZH2 stability through direct protein interactions, highlighting a coordinated epigenetic regulatory axis. Multi-omics studies have revealed that SETD2 loss induces aberrant DNA methylation and activates oncogenic signaling pathways, whereas EZH2 overexpression cooperates with PI3K-AKT pathway dysregulation to drive castration-resistant prostate cancer. Although inhibitors targeting SETD2 (e.g., EZM0414) and EZH2 (e.g., tazemetostat) demonstrate antitumor activity in preclinical models, their clinical efficacy remains constrained by drug resistance and tumor microenvironment heterogeneity. Emerging evidence suggests that combining epigenetic therapies with immunotherapy may enhance therapeutic outcomes. This review comprehensively systematically examines the molecular mechanisms underlying the SETD2/EZH2 axis in prostate cancer, providing a theoretical foundation for developing precision therapies based on SETD2- or EZH2-mediated epigenetic modifications.

Background: Tonsillar squamous cell carcinoma (TSCC) is characterized by a high tendency to metastasize to lymph nodes, significantly impacting the treatment modality and recurrence rates in head and neck cancer patients. Therefore, the development of accurate predictive models, such as nomograms, is imperative for the early identification of risk factors associated with lymph node involvement. Various lymph node classification systems, including the number of positive lymph nodes (NPLNs), the ratio of positive lymph nodes (pLNRs), and the logarithm of the odds of positive lymph nodes (LODDS), have been proposed to provide prognostic information. However, the optimal system for classifying lymph nodes remains uncertain, necessitating further investigation to determine which system offers the most accurate prediction of patient outcomes. Thus, our objective was to identify the most effective prognostic nomogram for predicting outcomes in TSCC patients. Material and Methods: In this study, we retrospectively analyzed data from 1,775 TSCC patients extracted from the Surveillance, Epidemiology, and End Results (SEER) database, following predefined criteria for inclusion. We evaluated the performance of prognostic models using Harrell's concordance index (C-index) and Akaike information criterion (AIC). Subsequently, variables were utilized to construct nomograms for predicting cancer-specific survival and overall survival. Nomograms' predictive capabilities were assessed using Integrated Discrimination Improvement (IDI) and Net Reclassification Improvement (NRI). Results: The nomogram comprising pLNR, LODDS, and NPLN showed superior efficacy in predicting the survival outcome of patients with laryngectomy for TSCC. Conclusion: The nomograms developed in this study have the potential to serve as valuable tools for forecasting patient survival following surgical interventions for TSCC.

Background: The expression pattern and functions of CBX4 in prostate cancers remain ambiguous. This study aims to investigate the performance of CBX4 in prostate cancer progression and preliminary inquiry potential mechanisms. Methods: The GEPIA data website was utilized to evaluate the expression patterns of CBX families and their correlations with prognosis. The "clusterprofiler" package was used for GSEA analysis. Seurat and CellChat package were used to analyze the single-cell expression profiles. The RT-qPCR, western blot and IHC staining were performed to detect the expression of CBX4 in prostate cancer tissues or cell lines. The cell functional experiments were performed, including MTT, colony formation assay, Transwell assay and scratch assay. Western blot was conducted to explore the regulation of CBX4 on EMT markers and PI3K/AKT pathway markers. Results: CBX4 was significantly up-regulated at tissue and cell levels in prostate cancer. High expression level of CBX4 was closely associated with advanced stage and poor prognosis. Of note, CBX4 was observed to promote immunosuppressive tumor environment via PDGF, VEGF, WNT signaling by cell-cell communications. In vitro experiments confirmed the expression level. Cell function and western blot proved the down-regulation of CBX4 dramatically inhibited the proliferation, invasion and migration of prostate cancer cells by targeting PI3K/AKT signaling. Conclusion: CBX4 might serve as a potential oncogene in prostate cancer progression. This study provides a new target for the treatment of prostate cancer.

Breast cancer remains a major global health burden, necessitating improved prognostic markers and therapeutic strategies. This study investigates the role of class II major histocompatibility complex transactivator (CIITA), a master regulator of major histocompatibility complex class II(MHC-II) gene expression, in breast cancer. Although CIITA is well recognized for its role in antigen presentation in immune cells, its function in tumor immunity and prognosis remains underexplored. Through integrative bioinformatics analyses using The Cancer Genome Atlas (TCGA) and other datasets, we demonstrate that high CIITA expression is associated with favorable clinical outcomes and enhanced immune activation in breast cancer. CIITA levels correlate with increased infiltration of antitumor immune cells, elevated expression of immune checkpoint genes, and enrichment of immune-related pathways. Immunohistochemical staining of breast cancer tissues further confirms CIITA protein expression patterns. Moreover, functional enrichment analyses suggest that CIITA may influence tumor-immune interactions by modulating immune response pathways. A prognostic nomogram incorporating CIITA expression shows robust predictive value for overall survival, offering potential clinical utility. These findings highlight CIITA as a promising prognostic biomarker and immunomodulatory target in breast cancer, shedding light on its role in shaping the tumor immune microenvironment.