Journal of Cancer最新文献

Background: Gastric cancer remains one of the most common causes of cancer death, with a notably high incidence in East Asian countries. Regulatory T cells (Tregs) suppress antitumor immunity in the tumor microenvironment, and recent studies have identified C-C motif chemokine receptor 8 (CCR8) as a selective marker for tumor-infiltrating activated Tregs. However, the role of CCR8⁺ Tregs in gastric cancer remains unclear. Methods: This study retrospectively analyzed 80 gastric cancer patients who underwent curative resection. Immunohistochemistry dual staining for CCR8/Foxp3 and granzyme B/CD8 was performed, followed by automated image analysis and spatial profiling. The correlation between CCR8⁺ Tregs and CD8⁺ T cells, as well as their prognostic significance, was evaluated. Results: CCR8⁺ Treg density positively correlated with CD8⁺ T cell infiltration. However, a low CD8⁺ T cell/CCR8⁺ Treg ratio was significantly associated with worse recurrence-free survival (P = 0.023). Reduced granzyme B expression was observed in CCR8⁺ Treg-dense hotspots, suggesting the presence of a localized immunosuppressive environment. Spatial analysis revealed that CCR8⁺ Tregs were preferentially localized at the tumor invasion front. Furthermore, distance analysis showed that fewer CD8⁺ T cells were present around CCR8⁺ Tregs than around CCR8⁻ Tregs, suggesting a localized immunosuppressive effect that may restrict CD8⁺ T cell proliferation. Conclusions: Our findings suggest that CCR8⁺ Tregs suppress antitumor immunity in gastric cancer by affecting surrounding CD8⁺ T cells through spatial segregation. Targeting CCR8⁺ Tregs may offer a promising strategy to improve the efficacy of immunotherapy in gastric cancer.

Background: Pancreatic neuroendocrine tumors (PanNETs) are rare neoplasms with an increasing incidence. This study aims to validate the clinical relevance of the WHO 2017 classification system in the Taiwanese population and identify independent prognostic factors for patients with PanNETs. Materials and methods: We conducted a retrospective analysis of 176 patients with PanNETs from the Chang Gung Medical Hospital at Linkou in Taiwan, spanning the years 2009 to 2022. Pathology reports were reassessed according to the WHO 2017 classification. Clinical characteristics, treatment patterns, and survival outcomes were documented, with subgroup analyses to compare grade 3 (G3) neuroendocrine tumors and neuroendocrine carcinomas (NEC). Results: The overall 5-year survival rate was 58.7%, with median survival of 107.6 months. Survival rates showed clear stratification across WHO 2017 classifications: G1 (83.1%, median 141.0 months), G2 (55.0%, median 105.2 months), G3 (14.6%, median 21.5 months), and NEC (9.4%, median 19.6 months). Multivariate analysis identified five independent prognostic factors: age over 60 years (HR 1.70), tumor size >2cm (HR 1.893), lymph node involvement (HR 1.801), distant metastasis (HR 3.042), and NEC classification (HR 2.382). NEC demonstrated significantly higher lymph node involvement (81% vs 48%, p=0.026), higher Ki-67 index (69 vs 43.8, p<0.001), and higher rates of metastases compared with G3 NET. Conclusions: Our findings validate the prognostic utility of the WHO 2017 classification, particularly in differentiating NET G3 from NEC. This refined classification system, combined with identified prognostic factors, provides valuable guidance for clinical decision-making and treatment selection in patients with PanNETs.

Objective: Glutamic pyruvic transaminase 2 (GPT2) promotes the initiation and progression of various cancers. However, its regulatory role in bladder cancer (BCa) remains unclear. In this study, we aimed to validate the role of GPT2 in BCa using bioinformatics analysis combined with in vitro and in vivo experiments. Methods: We utilized bioinformatic approaches to download GPT2-related genomic datasets and preliminarily analyzed their expression profile and clinical significance in BCa. Multidimensional predictions regarding the mechanisms by which GPT2 influences BCa progression were generated by integrating diverse bioinformatic analyses. These predictions were further validated through in vitro and in vivo experiments to confirm GPT2 expression patterns and pro-tumorigenic mechanisms. Conclusion: GPT2 is highly expressed in BCa and is associated with a poor prognosis in patients with BCa. GPT2 has been implicated in tumorigenesis, immune cell infiltration, cell proliferation, epithelial-mesenchymal transition (EMT), and maintenance of stemness. GPT2 knockdown reduced EMT and stemness in BCa cells, suppressed their proliferation, invasion, and migration, and inhibited subcutaneous tumor formation and growth in nude mice. Investigating and elucidating the mechanism of GPT2 in bladder cancer (BCa) provides novel evidence for further understanding the pathogenesis of bladder cancer and developing subsequent therapeutic strategies.

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.