Journal of Cancer Research and Clinical Oncology最新文献

Gastric cancer remains a significant global health challenge due to its aggressive behavior, high mortality rates, and limited treatment success. Growing research underscores the critical role of SUMOylation, a reversible post-translational modification, in regulating key cellular processes such as DNA repair, gene expression, genomic stability, and signaling pathways. Aberrant SUMOylation is closely linked to gastric cancer development, metastasis, and resistance to therapies, positioning it as a potential therapeutic target. This review consolidates current knowledge of the SUMOylation system, which involves activating (E1), conjugating (E2), and ligating (E3) enzymes, alongside SUMO-specific proteases (SENPs) that reverse the modification. We explore how SUMOylation influences cancer-promoting and tumor-suppressing pathways by stabilizing or degrading critical proteins, modulating immune responses, driving epithelial-mesenchymal transition, and contributing to chemoresistance. Furthermore, we discuss promising therapeutic approaches targeting SUMOylation, including small-molecule inhibitors, natural bioactive compounds, and synthetic lethal strategies that exploit SUMO pathway weaknesses. Preclinical studies suggest these approaches could enhance chemotherapy and immunotherapy effectiveness, offering new precision treatment options. Deepening our understanding of SUMOylation in gastric cancer is vital for developing innovative, mechanism-driven therapies to improve patient outcomes.

Aim: The clinical management of gastric cancer (GC) is frequently challenged by the development of drug resistance, leading to poor patient outcomes. This review aims to explore the role of ferroptosis, an iron-dependent form of programmed cell death driven by lipid peroxidation, in overcoming this therapeutic hurdle. Our objective is to provide a theoretical foundation for developing novel strategies to reverse drug resistance in GC by targeting the ferroptosis pathway.

Methods: This review systematically elucidates the core regulatory mechanisms of ferroptosis and analyzes its key role in mediating drug resistance in GC. We synthesize current literature to explore potential therapeutic strategies that leverage ferroptosis induction to sensitize cancer cells. Furthermore, we critically examine the complex interplay between ferroptosis and the tumor microenvironment (TME) and discuss the challenges associated with translating these findings into personalized treatment approaches, integrating insights from emerging technologies.

Results: Our analysis confirms that ferroptosis is governed by a precise regulatory network involving glutathione metabolism, lipid peroxidation, and iron homeostasis, which is frequently dysregulated in GC. We identify that key mechanisms of conventional drug resistance are linked to the evasion of ferroptosis. Consequently, several potential therapeutic strategies, including the use of ferroptosis inducers (FINs) and combination therapies, show promise in resensitizing resistant GC cells. The review also highlights the dual role of the TME, which can either suppress or promote ferroptosis, adding a layer of complexity. Finally, we identify significant challenges in patient stratification and the need for reliable biomarkers to achieve personalized ferroptosis-based therapies.

Conclusion: Targeting ferroptosis presents a promising and innovative research avenue for reversing drug resistance in gastric cancer. Strategies designed to induce ferroptosis effectively overcome common resistance mechanisms and hold significant therapeutic potential. Future research must focus on integrating multi-omics technologies and advanced drug delivery systems to decipher the complex regulatory networks of ferroptosis within the TME and to develop biomarkers for personalized treatment, thereby paving the way for improved clinical outcomes.

Objective: The management of pulmonary metastases (PM) from head and neck adenoid cystic carcinoma (ACC) remains controversial, with limited evidence guiding the choice between surgical and non-surgical strategies. This study aimed to compare long-term survival outcomes between patients undergoing surgical resection and those receiving non-surgical management for ACC-derived PM.

Methods: We conducted a retrospective analysis of 204 patients with pulmonary metastases from head and neck ACC treated at our institution between January 2010 and December 2024. Patients were categorized into Surgery (n = 108) and Non-Surgery (n = 96) groups. To address selection bias and improve causal inference in this observational study, propensity score matching (PSM) was performed based on key clinical variables, generating 68 well-matched pairs. Overall survival (OS) and progression-free survival (PFS) were compared using Kaplan-Meier analysis and Cox proportional hazards models.

Results: Before matching, the Surgery group demonstrated significantly higher 5-year OS (97.73% vs. 84.2%, P = 0.0004) and PFS (89.39% vs. 74.66%, P = 0.021). After PSM, the survival advantage persisted, with the Surgery group showing improved 5-year OS (95.75% vs. 82.91%, P = 0.0063) and PFS (86.93% vs. 73.86%, P = 0.0039). Multivariate analysis confirmed surgical resection as an independent prognostic factor for improved OS (HR = 0.08, 95% CI: 0.01-0.42, P = 0.0032), alongside tumor grade, presence of pleural effusion, and International Registry of Lung Metastases (IRLM) stage.

Conclusions: In this propensity-matched analysis, surgical metastasectomy was associated with significantly improved survival in selected patients with ACC lung metastases, supporting its consideration as a valuable therapeutic option for oligometastatic disease within a multidisciplinary framework.

Purpose: Complications such as graft-versus-host disease (GVHD), hepatic sinusoidal obstruction syndrome, and infections compromise the success of allogeneic hematopoietic stem cell transplantation (HSCT) as a treatment modality for malignant or genetic diseases. Identification of beneficial non-human leukocyte antigens (HLA), such as cytokines, is one approach to reduce the rate of unintended events. This study investigated the association between single-nucleotide polymorphisms (SNPs) of the gene of the proinflammatory cytokine interleukin-1 (IL-1) and treatment outcomes after allogeneic HSCT in a pediatric population.

Methods: In our single-center study, we retrospectively analyzed a cohort of 270 children and their respective donors. They underwent allogeneic HSCT for the first time, and their conditioning regimen was myeloablative in all cases. We used polymerase chain reaction to genotype the SNPs of IL-1α rs1800587 (C > T), IL-1β rs16944 (C > T), and IL-1β rs1143627 (C > T). The outcome measures included overall survival (OS), event-free survival (EFS), relapse rate (RR), transplant-related mortality (TRM), and the occurrence of acute or chronic GVHD.

Results: The distribution of IL-1α rs1800587 genotype was as follows: we observed the CC genotype in 124 of 256 recipients (48.4%) and 132 of 270 donors (48.9%). We detected the CT genotype in 115 patients (44.9%) and 114 donors (42.2%) and found the homozygous TT genotype in 17 children (6.6%) and 24 of their donors (8.9%). The distribution of the SNP IL-1α rs1800587 is in Hardy-Weinberg equilibrium. The incidence of moderate or severe acute GVHD was significantly decreased in recipients receiving a donor transplant with the TT genotype (4% (TT) versus 25% (CC/CT); p = 0.028). We found no significant SNP IL-1α rs1800587 (C > T) associations for chronic GVHD, RR, TRM, EFS, and OS. For the other genotypes analyzed, IL-1β rs11644 (C > T) and IL-1β rs1143627 (C > T), we also found no significant associations for acute and chronic GVHD, RR, TRM, EFS, and OS, neither in donors nor in recipients. The results of the multivariate analysis revealed a hazard ratio of 0.17 (confidence interval 0.0229-1.27), and a trend that IL-1α rs1800587 could be an independent risk factor for acute GVHD (p = 0.084).

Conclusion: Our study identified the donor IL-1α rs1800587 CC/CT genotype as a possible genetic risk factor for developing moderate to severe acute GVHD (grade II - IV) in pediatric patients who underwent allogeneic HSCT. Once confirmed in further studies, these results may influence the donor selection and prophylaxis to decrease the risk of acute GVHD in children.

Background: The lncRNA FOXD3-AS1 shows abnormal expression in various tumors, but its role in prostate cancer (PCa) remains unclear.

Objective: This study sought to examine FOXD3-AS1 expression patterns in PCa and its molecular role in regulating PEG10 through miR-491-5p.

Methods: The methodological approach involved the application of RT-qPCR to determine the expression profiles of FOXD3-AS1, miR-491-5p, and PEG10 across PCa tissues and in vitro cell systems; subcellular localization analysis determined the cytoplasmic distribution of FOXD3-AS1; Cell proliferation, migratory and invasive capacities, as well as apoptosis, were assessed using CCK-8, transwell, and flow cytometric assays, respectively; dual-luciferase reporter assays verified the targeting relationships between molecules; statistical software was used for data analysis.

Results: FOXD3-AS1 demonstrated substantial upregulation within prostate carcinoma tissues and cultured cells and was found to be predominantly localized within the cytoplasmic compartment. Functional experiments demonstrated that depleting FOXD3-AS1 strongly impeded cell multiplication, spread, and penetration, and enhanced apoptotic activity. Rescue assays demonstrated that co-intervention of miR-491-5p or its downstream target PEG10 could counteract the tumor-suppressive effects induced by FOXD3-AS1 silencing. Mechanistically, FOXD3-AS1 functions as a ceRNA, sequestering miR-491-5p to attenuate its repression of PEG10.

Conclusion: FOXD3-AS1 influences PCa cell behavior via the miR-491-5p/PEG10 axis.

Chronic obstructive pulmonary disease (COPD) and lung cancer are highly correlated and frequently co-occur. Any degree of COPD significantly increases the risk of developing lung cancer, suggesting they may share common pathogenic mechanisms. The hypoxia-inducible factor 1 (HIF-1) signaling pathway, a complex regulatory network for cellular sensing and response to hypoxia, is abnormally activated in both COPD and lung cancer. Chronic inflammation, immune microenvironment imbalance, extracellular matrix remodeling, epithelial-mesenchymal transition, angiogenesis, and epithelial differentiation, all closely related to the HIF-1 pathway, lie at the intersection of both diseases. Consequently, the HIF-1 pathway is proposed as a potential molecular mechanism underpinning the occurrence, progression, and poor prognosis of lung cancer with COPD (LC-COPD). In this review, we focus on the role and mechanisms of HIF-1 in advancing LC-COPD, highlighting its promising potential as a therapeutic target.

Aim: To explore the clinical application value of modified overlap anastomosis for Siewert type II and III adenocarcinoma of esophagogastric junction, and to further evaluate its feasibility and safety.

Methods: We retrospectively analyzed clinical data from 222 patients with Siewert type II and III adenocarcinoma of the esophagogastric junction admitted to our hospital between January 2017 to October 2023. All patients underwent laparoscopic total gastrectomy with D2 lymph node dissection. 64 patients underwent esophagojejunostomy with modified overlap anastomosis, and 158 patients were operated using the circular stapled anastomosis. Variables that are statistically different were compared between groups using propensity score matching (PSM). The differences in surgical-related indicators and clinical outcomes for the two groups were compared. Finally, we analyzed the risk factors associated with esophagojejunostomy (EJ)-related complications.

Results: There was no statistically significant difference between the two groups of patients in terms of BMI, gender, age, and tumor-related information (P value > 0.05). However, there was then a difference in preoperative hemoglobin between the two groups. To eliminate heterogeneity, we combined patients with PSM. In terms of intraoperative conditions and postoperative recovery after PSM, compared with the circular stapled anastomosis group, the modified overlap group showed the shorter total operation time, shorter the length of the auxiliary incision, shorter time to the soft diet intake, milder postoperative pain. In terms of postoperative complications and overall survival after PSM, the modified overlap group can reduce the probability of abdominal infection and there was no difference in overall survival (OS) and postoperative late complications between the two groups. Multivariate analysis showed that the Siewert type [odds ratio (OR), 0.355; 95% confidence interval (CI) 0.189-0.639, P value = 0.005] was independent risk factors of EJ-related complications.

Conclusion: Although the modified overlap group had slightly lower total protein after surgery, it had advantages in operation time, the length of the auxiliary incision, the soft diet intake time, postoperative pain, abdominal infection. General surgeons should exercise heightened vigilance in preventing EJ-related complications for patients classified as Siewert type II. In summary, modified Overlap anastomosis is safe and reliable. It has clinical application value.

Background: Metabolic reprogramming, especially lipid metabolism, is crucial in cancer progression and treatment resistance. Apolipoproteins are crucial targets for research as they regulate autophagy, oxidative stress, and chemoresistance. A systematic bibliometric and bioinformatics approach is necessary to identify trends and elucidate the molecular mechanisms linking apolipoproteins to cancer.

Methods: A systematic bibliometric analysis was conducted using the Web of Science Core Collection and PubMed. VOSviewer, CiteSpace, and the Bibliometrix R package were employed to analyze and visualize co-authorship networks, keyword trends, and other key metrics. Bioinformatics analysis integrated protein-protein interaction network construction, hub gene identification, and enrichment analysis using R-based pipelines.

Results: China has led the international research on apolipoproteins and cancer since 2015. Research has shifted from molecular studies to clinical applications, highlighting the roles of apolipoproteins in cancer risk, progression, and prognosis. Bioinformatic analysis identified key genes represented by APOA1 (apolipoprotein A1), APOE (apolipoprotein E), APOA2 (apolipoprotein A2), and ALB (Albumin) as central regulators in lipid localization, cholesterol metabolism, insulin resistance, and the peroxisome proliferator-activated receptors (PPARs) signaling pathways.

Conclusions: This study combines bibliometric and bioinformatic approaches to explore apolipoprotein research in cancer. The research trend revealed apolipoproteins with the most research potential in a specific cancer type, as confirmed in the clinical trials. Bioinformatic research found the key genes regulating several essential lipid-related pathways. This article clearly outlined the research landscape and frontiers of this field by combining various databases and methods, highlighting the significant potential of apolipoproteins in the development of novel cancer medications.

Aldehyde dehydrogenases (ALDHs) are responsible for the NAD(P)⁺-dependent oxidation of aldehydes into carboxylic acids, fulfilling key roles in detoxification, antioxidant defense, biosynthesis, and regulatory processes. Elevated expression and activity of ALDH isoenzymes have been documented in various human cancers, where they are linked to cancer recurrence. While the human genome encodes 19 functional ALDH genes, aldehyde dehydrogenase 1B1 (ALDH1B1) has emerged as a critical enzyme in diverse human pathologies. ALDH1B1 is a major mitochondrial enzyme involved in detoxifying lipid peroxidation by-products and metabolizing various aldehyde substrates. Notably, both low and high ALDH1B1 expression levels contribute to tumor progression and with marked variability observed across different tumor types. This review summarizes the essential functions and potential ALDH1B1 mechanisms in the tumor initiation, progression, metastasis, and therapeutic responses across cancer types. Our analysis indicates that ALDH1B1 is a potential therapeutic target for cancer therapy.

Background: Skin cutaneous melanoma (SKCM) is an aggressive malignancy with limited prognostic markers. Mitochondrial permeability transition (MPT)-driven necrosis has been implicated in tumor progression and immune regulation, yet its role in SKCM remains unclear.

Methods: 39 MPT-driven necrosis-related genes (MPTDNRG) were retrieved from Molecular Signatures Database (MSigDB). Using TCGA-SKCM and GTEx datasets, differentially expressed genes (DEGs) were identified and incorporated into Cox and LASSO analyses. An MPT-driven necrosis-related gene signature (MPTDNRGS) was constructed. The signature was validated in GEO cohorts (GSE19234, GSE65904). A nomogram integrating clinical factors was established to assess predictive performance. Functional enrichment, immune infiltration, and checkpoint responsiveness were evaluated. Single-cell RNA-seq (scRNA-seq) datasets were further analyzed to map cell-type-specific expression and T-cell trajectories.

Results: A five gene signature (BIRC3, CASP7, ENDOG, PRF1, PRKCB) stratified patients into high and low risk groups with distinct survival outcomes. The nomogram achieved strong predictive accuracy (3-year AUC = 0.772). High risk patients exhibited suppressed immune activation, lower T-cell infiltration, and reduced predicted response to immune checkpoint inhibitors. Single cell analysis revealed higher MPTDNRGS scores in tumor-infiltrating T cells than in normal controls. Pseudotime trajectories showed cytotoxic T cells transitioning to immunosuppressive phenotypes, marked by progressive BIRC3 upregulation. Elevated BIRC3 correlated with immune inhibitory markers and enrichment of TGF-β and IL6/JAK/STAT3 pathways.

Conclusion: We established and validated a novel MPT-driven necrosis-based prognostic model for SKCM. This model reliably predicted patient outcomes and immune status. BIRC3 emerged as a potential regulator of T-cell dysfunction and a promising therapeutic target in SKCM.