Journal of Cancer最新文献

Securin is a key regulator of chromosome segregation during mitosis. Dysregulation of securin triggers chromosomal instability (CIN) and aneuploidy, which are hallmarks of many solid tumors, including breast cancer (BC). Recent studies have revealed securin's multifaceted roles in the progression of BC. Overexpression of securin not only enhances the malignant behaviors of BC cells but also correlates with poor clinical outcomes in patients, suggesting its potential as both a therapeutic target and prognostic biomarker. Although interest in securin is growing, comprehensive reviews on its role in BC are sparse. In this review, we summarize the biological function of securin. We then focus on the expression patterns of securin in BC and related experimental models, and their association with CIN. Subsequently, we discuss the significance of securin as a prognostic marker for BC. Lastly, we explore how securin influences the malignant behaviors of BC cells. This review emphasizes the critical connection between CIN and BC pathobiology mediated by securin and offers insights for future research into securin-related mechanisms and therapeutic strategies.

Colorectal cancer (CRC) is a globally common malignancy, whose complex disease etiology involves a genetic element. Nuclear enriched abundant transcript 1 (NEAT1), a long noncoding RNA (lncRNA) gene, has been demonstrated to play a key role in cancer development. To clarify the potential effect of NEAT1 gene polymorphisms on CRC susceptibility, three NEAT1 single-nucleotide polymorphisms (SNPs), including rs3825071, rs3741384, and rs512715, were assessed in 485 CRC patients and 485 sex- and age-matched non-cancer controls. We did not detect any significant association of these SNPs with the occurrence and clinicopathological features of CRC. Nevertheless, one SNP of NEAT1 gene, rs3825071, was found in association with the distant metastasis (CT+TT: CC, OR, 2.644; 95% CI, 1.328-5.263; p=0.005) among relatively younger patients (< 65 years old), indicating an age-specific effect of NEAT1 gene polymorphisms on the spread of CRC. Our stratification analysis revealed that the association of rs3825071 with CRC metastasis is anatomical site-specific, as cases of colon tumors but not of rectal tumors who bear at least one polymorphic allele of rs3825071 more commonly developed metastasis. Further exploration using the datasets from the Genotype-Tissue Expression (GTEx) Portal and The Cancer Genome Atlas (TCGA) showed that rs3825071 genotypes affected NEAT1 expression in the colon tissues, and elevated NEAT1 levels were associated with a worse survival rate in relatively younger patients (< 65 years old) with colon adenocarcinoma. These data suggest that altered expression levels of NEAT1 due to genetic polymorphisms may influence the progression of colon cancer.

Since the discovery of ferroptosis, which plays an important role in gastric cancer (GC), its activation has been crucial for developing tumor therapeutic strategies. Recently, ferroptosis activation has become a research hotspot for GC treatment approaches. Energy and metabolism dysfunctions involving lipids, amino acids, iron, sugars, and nucleotides caused by GC cells in a typical hypoxic microenvironment are important disease characteristics. However, the immune escape mechanism of GC cells limits the occurrence of programed cell death, a controllable form of which is ferroptosis. First, excessive reactive oxygen species production induces changes in intracellular iron ion levels, resulting in an imbalance in the antioxidant defense system. Finally, excessive accumulation of intracellular lipid peroxidation byproducts destroys cell membrane consistency and causes cell death. The promotion of ferroptosis in GC cells has been widely employed as a method for inhibiting tumor growth and chemotherapy resistance, which is helpful for developing anti-GC targeted treatments. Because GC cells are sensitive to ferroptosis-inducing agents, some traditional antitumor drugs (e.g., cisplatin) and Chinese herbal or natural medicines (e.g., artemisinin) exert anticancer effects by inducing this process. In this article, we summarize the basic molecular mechanisms underlying ferroptosis and the involved tumor markers, along with associated chemotherapy drugs and natural medicines. To activate ferroptosis in GC, new targeted drug therapies can be used within the clinical treatment field to kill GC cells and enhance tumor sensitivity to chemotherapy.

Background: Preventing the emergence and persistence of cancer stemness represents a promising strategy to reduce tumor aggressiveness and therapeutic failure. Cancer stem cells (CSCs), which contribute significantly to therapy resistance, recurrence, and metastasis, are sustained in part by metabolic reprogramming that enhances survival and self-renewal under stress conditions. Methods: To model the hypoxic core of solid tumors, three-dimensional (3D) glioblastoma (GBM) spheroid cultures were generated using human U87, U118, U138, and U251 cell lines and compared to their respective two-dimensional (2D) monolayer cultures. Total RNA was extracted, and gene expression was analyzed via RT-qPCR and targeted gene arrays. Transient gene silencing was performed using specific siRNAs, while pharmacological intervention involved treatment with (-)-Epigallocatechin-3-gallate (EGCG), a bioactive phytochemical derived from green tea. Adipogenesis was evaluated using Oil Red O staining. Results: Compared to conventional 2D cultures, 3D spheroids exhibited elevated expression of hypoxia-inducible factor-1 alpha (HIF-1α) and upregulation of peroxisome proliferator-activated receptor gamma (PPARγ), identified through adipogenesis array screening. Adipogenic activity persisted in the 3D spheroid model, and EGCG treatment effectively suppressed the upregulation of HIF-1α and PPARG transcripts. This led to a significant downregulation of adipogenic genes (CEBPD, FOXO1, BMP2, BMP7) and CSC-associated markers (CD44, PROM1, ABCB5, ABCG2), accompanied by reduced spheroid growth. Conclusions: These findings underscore EGCG's chemopreventive potential in disrupting early HIF-1α-mediated molecular pathways that reinforce GBM stemness. By targeting hypoxia-driven metabolic reprogramming, EGCG offers a dietary-based approach to modulate the CSC niche and potentially delay or prevent GBM progression. Moreover, the use of 3D spheroid models highlights their relevance in preclinical chemoprevention research, bridging the gap between simplistic 2D cultures and the complex biology of solid tumors.

Distinct from apoptosis, ferroptosis is intricately associated with intracellular iron ions and oxidative stress, representing a unique form of cell demise. In the treatment of ovarian cancer (OC), it assumes a crucial role, as research suggests its association with patient prognosis. This investigation delves into the correlation between genes associated with ferroptosis and the prognosis of OC, providing insights into its pathogenesis. Through the examination of mRNA expression using TCGA, ICGC, and GTEx databases, we identified a set of five pivotal genes (CD44, FTH1, ALOX12, SLC7A11, CRYAB) forming a prognostic model. Their regulation affects various aspects of OC, including the cell cycle, proliferation, invasiveness, immune response, and drug tolerance. To summarize, ferroptosis significantly impacts the prognosis of OC, and the targeting of relevant pathways holds potential for enhancing treatment outcomes, thereby guiding future research and personalized therapeutic strategies.

Capsaicin is the pungent and bioactive compounds of Capsicum annum. Previous studies have demonstrated the potent anti-tumor effect of capsaicin on various human malignancies by experiments in vitro or in vivo. However, the mechanism underlying its antitumor efficiency is not fully elucidated. Cell cycle arrest is one of anti-proliferation mechanisms for anti-neoplastic drugs. The p21 protein, an important inhibitor of cell cycle progression, could block cyclin dependent kinases (CDKs) mediated activation of cyclins. As the downstream transcriptional factor of the Hh pathway, GLI1 plays a crucial role in cancer progression and prognosis evaluation. The aim of the present study is to explore the potential role of GLI1 in p21 mediated cell cycle arrest induced by capsaicin treatment in renal cell carcinoma (RCC) 786-O and Caki-1 cell lines. The results revealed that capsaicin could inhibit proliferation of RCC cells and cause G₀/G₁ cell cycle arrest in vitro. Besides, we discovered that the capsaicin treatment increased the expression of p21 protein and downregulated the expression of GLI1, suggesting that GLI1 was involved in the p21 mediated G₀/G₁ arrest induced by capsaicin administration in RCC 786-O and Caki-1 cell lines. In conclusion, our study demonstrated that capsaicin could induce p21 mediated cell cycle arrest via suppressing GLI1 to inhibit RCC cell proliferation, which might be a promising therapeutic strategy in RCC.

Breast cancer is a lethal carcinoma impacting a considerable number of women across the globe. While preventive measures are limited, early detection remains the most effective strategy. Accurate classification of breast tumors into benign and malignant categories is important which may help physicians in diagnosing the disease faster. This survey investigates the emerging inclination and approaches in the area of machine learning (ML) for the diagnosis of breast cancer, pointing out the classification techniques based on both segmentation and feature selection. Certain datasets such as the Wisconsin Diagnostic Breast Cancer Dataset (WDBC), Wisconsin Breast Cancer Dataset Original (WBCD), Wisconsin Prognostic Breast Cancer Dataset (WPBC), BreakHis, and others are being evaluated in this study for the demonstration of their influence on the performance of the diagnostic tools and the accuracy of the models such as Support vector machine, Convolutional Neural Networks (CNNs) and ensemble approaches. The main shortcomings or research gaps such as prejudice of datasets, scarcity of generalizability, and interpretation challenges are highlighted. This research emphasizes the importance of the hybrid methodologies, cross-dataset validation, and the engineering of explainable AI to narrow these gaps and enhance the overall clinical acceptance of ML-based detection tools.

Background: The use of immune checkpoint inhibitors (ICI) and other targeted molecular agents for non-small cell lung cancer (NSCLC) has led to unprecedented rates of major pathologic response and improvements in overall survival. The aim of this study was to evaluate the prognostic significance of lymph node downstaging following neoadjuvant chemoimmunotherapy for resectable NSCLC. Methods: This study used retrospective data from the National Cancer Database (NCDB), which was queried for all patients diagnosed with NSCLC between 2017-2021 who underwent lung cancer surgery after receiving neoadjuvant chemoimmunotherapy. Only those staged as cN1 or cN2 were included. Patients were stratified according to post-therapy pathologic lymph node status, whether positive (ypN+) or negative (ypN-). Five-year overall survival (OS) was examined using Kaplan-Meier analyses with log-rank tests. Univariate and multivariate Cox regression analyses were conducted to identify significant predictors of survival. Results: Of the total 621 patients, 229 (37%) were diagnosed with cN1 disease and 392 (63%) with cN2. With neoadjuvant chemoimmunotherapy, 59% of cN1 and 40% of cN2 patients were down-staged to ypN0. While 5-year OS was not significantly different according to clinical N stage (76% for cN1 vs. 63% for cN2, p=0.08), higher post-therapy nodal staging correlated with poorer long-term survival (5-year OS of 84% for ypN0, 64% for ypN1, and 51% for ypN2, p <0.001). On multivariate analysis, cN1 to ypN+ (HR 2.56, p=0.009) and cN2 to ypN+ (HR 3.09, p=0.001) were predictors of worse OS compared to cN1 to ypN-, while the difference was not statistically significant for cN2 to ypN- (HR 1.01, p=0.051). Among ypN- patients, similar 5-year OS was seen among those who received adjuvant chemoimmunotherapy and those who did not (82.2% vs. 86.2%, p = 0.26). Conclusion: Patients receiving neoadjuvant chemoimmunotherapy for resectable NSCLC experience high rates of nodal down-staging. Achieving ypN0 status post-therapy strongly predicts favorable long-term survival in this population, while pretreatment cN stage becomes less prognostically relevant.

Background: Renal cell carcinoma (RCC) is a leading malignancy of the urinary system, with clear cell RCC (ccRCC) being the most prevalent subtype. Despite advances in treatment, the prognosis of advanced RCC remains poor, and the molecular mechanisms underlying its pathogenesis are not fully understood. Methods: This study utilized multiple renal cancer cohorts from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). By integrating Mendelian randomization (MR) analyses of expression quantitative trait loci (eQTL) and protein quantitative trait loci (pQTL), we investigated causal associations between candidate genes and RCC. Immune infiltration, drug sensitivity, and survival analyses were performed to further explore functional significance. In vitro experiments validated the biological role ofISOC1 in RCC progression. Results: We focused on ISOC1, a gene previously implicated in other malignancies but not well studied in RCC. Through integrative MR analysis, we identified ISOC1 as a novel RCC-associated gene, with potential tumor-suppressive functions in this specific context. ISOC1 expression was significantly linked to tumor immune infiltration, drug sensitivity, and patient prognosis. Functional assays demonstrated that ISOC1 knockdown promoted RCC cell proliferation, migration, and invasion. Conclusions: ISOC1 plays a critical role in RCC progression and may act as a tumor suppressor. These findings highlight ISOC1 as a potential biomarker for prognosis and a promising target for therapeutic intervention in RCC. Moreover, this study underscores the utility of MR-based integrative analyses in uncovering novel molecular mechanisms and therapeutic targets for cancer.

Background: While a link between coronavirus disease 2019 (COVID-19) and prostate cancer (PrCa) has been observed in clinical settings, the shared underlying genetic influences remain unclear. Methods: Leveraging summary statistics from the hitherto largest genome-wide association studies (GWASs) of European-ancestry populations, we performed the first comprehensive genome-wide cross-trait analysis to investigate the shared genetic architecture, pleiotropy, and potential causal relationships between three COVID-19 phenotypes and PrCa. Results: We found no evidence of significant genome-wide genetic correlations between COVID-19 phenotypes and PrCa (P > 0.05). However, after partitioning the whole genome into 2353 independent regions, we observed significant local genetic correlations at chromosome 1 (chr1), chr7, and chr14 for PrCa with at least one COVID-19 phenotype (P < 0.05/2353). Cross-trait meta-analysis identified 22 independent single nucleotide polymorphisms (SNPs) shared between PrCa and at least one COVID-19 phenotype, totalling 25 associations, including 2 with infection, 14 with hospitalization, and 9 with critical illness. Transcriptome-wide association study (TWAS) revealed eight distinct shared genes (CCHCR1, TCF19, ADAM15, HLA-C, CYP21A1P, HCP5, ATF6B, and HLA-DQB2), predominantly enriched in tissues of the respiratory, neurological, and reproductive systems. Bidirectional Mendelian randomization (MR) demonstrated no causal association between COVID-19 phenotypes and PrCa. Conclusions: Using a multi-layered analytical framework, our study provides novel insights into the shared genetic bases between COVID-19 phenotypes and PrCa, supported by significant local genetic correlations, pleiotropic SNPs, and shared genes. These findings highlight common biological mechanisms rather than direct causal relationships, suggesting the limited benefits of additional PrCa screening in COVID-19 survivors. Furthermore, the identified genes represent promising targets for future mechanistic research and clinical interventions, warranting further validation.