Journal of Cancer Research and Clinical Oncology最新文献

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.

Background: Early detection of hepatocellular carcinoma (HCC) represents a significant clinical challenge due to the lack of effective biomarkers. Previous studies have revealed abnormal hypermethylation of RASSF1A and TSPYL5 in HCC tissues, prompting further investigation into their utility as potential biomarkers for HCC diagnosis. In this study, we explored the clinical value of RASSF1A/TSPYL5 methylation alone and in combination with AFP protein as diagnostic biomarkers for early HCC detection.

Methods: Bioinformatics analysis using MethSurv, LinkedOmics, and Wanderer was conducted to assess the methylation levels of RASSF1A and TSPYL5 in HCC tissue samples from the public database. The methylation status of these two genes was validated in cell lines and plasma samples from HCC patients. Furthermore, the ARTHCC model, comprising the measurement of RASSF1A and TSPYL5 methylation and AFP protein, was developed and validated using plasma samples from HCC patients.

Results: Our comprehensive bioinformatic analysis revealed that TSPYL5 CpG sites were hypermethylated in HCC tissue samples, particularly among CpG island and shore regions. Approximately 40% of CpG sites of RASSF1A also exhibited hypermethylation. The hypermethylation status of TSPYL5 may be associated with portal vein tumor thrombus (PVTT) in HCC patients. Combining analysis of RASSF1A and TSPYL5 methylation levels with AFP protein, the ARTHCC model demonstrates superior sensitivity and specificity for detecting HCC in both the discovery and validation cohorts. Notably, the ARTHCC model consistently exhibited robust performance across different subgroups.

Conclusions: This study provides compelling evidence that the combination of RASSF1A/TSPYL5 methylation and AFP protein is a promising biomarker panel for the early detection of HCC. The ARTHCC model demonstrates remarkable sensitivity and specificity, outperforming AFP.

Purpose: Hemangioblastoma is an uncommon tumor of uncertain histogenesis, primarily found in the central nervous system. However, extraneural cases have been reported in visceral organs such as the kidneys, pancreas, peritoneum, and liver. Hemangioblastoma occurring in the gastrointestinal tract is extremely rare, with only 4 cases can be retrieved. Here, we presented a case of rectal hemangioblastoma.

Methods: A 59-year-old woman sought medical attention for altered stool consistency and the colonoscopy revealed a submucosal lesion in the rectum. Subsequently, she underwent endoscopic submucosal dissection. Grossly, the excised lesion was a broad-based polypoid mass measuring 1.2 × 0.8 × 0.8 cm, with a grayish-white appearance and no signs of hemorrhage or necrosis. Histologically, the tumor consisted of a rich network of thin-walled blood vessels interspersed with vesicular neoplastic cells, with minimal mitotic activity. Immunohistochemistry found that neoplastic cells were positive for D2-40, and β-catenin showed normal membranous staining pattern. No pathogenic mutations in the VHL gene were detected by NGS in this sample. However, we found genetic alterations in other genes potentially associated with the pathogenesis of hemangioblastoma, such as TSC, SDH and PTEN.

Results: Based on the above findings, the diagnosis of hemangioblastoma was made. The differential diagnosis included hemangioma, lymphangioma, neuroendocrine tumor, metastatic renal cell carcinoma, perivascular epithelioid cell tumor, gastrointestinal stromal tumor, and well-differentiated liposarcoma.

Conclusion: This case underscored the importance of considering hemangioblastoma in the differential diagnosis of rectal submucosal lesions. It highlighted the need for a thorough diagnostic approach that integrates colonoscopic evaluation with histopathological examination, particularly in patients presenting with altered stool consistency or melena. Furthermore, the NGS results implicated that TSC, SDH and PTEN may contribute to hemangioblastoma development. These alterations could constitute a novel diagnostic signature, a premise that warrants definitive investigation through larger, multi-institutional studies.

Background: To evaluate patient satisfaction with different incision types in breast reconstruction surgery in China and to explore the factors related to these outcomes.

Methods: This single-center, retrospective cohort study included patients who underwent breast reconstruction at Hubei Cancer Hospital from September 2022 to September 2024. The patients were divided into four groups based on the incision type: (1) lateral axillary incision, (2) radial incision, (3) inferolateral inframammary fold incision, and (4) endoscopic-assisted surgery. Patient-reported outcomes (PROs) were collected ≥ 3 months after surgery using the Breast Cancer Core Scale (BREAST-Q) V2.0, the EuroQol five-dimension five-level health questionnaire (EQ-5D-5L), and the Decision Regret Scale (DRS). It should be noted that the type of incision was non-randomly allocated, although multivariate regression was performed to adjust for potential confounding factors.

Results: A total of 209 patients were included in this study. 34 (16.3%), 67 (32.1%), 64 (30.6%), and 44 (21.1%) patients underwent lateral axillary incision, radial incision, inferolateral inframammary fold incision, and endoscopic-assisted surgery, respectively. The endoscopic-assisted surgery group had the highest satisfaction (59.00 [IQR 57.75, 65.00]), and the radial incision group had the lowest satisfaction (53.00 [IQR 47.00-60.50]) (P = 0.007). Multivariable linear regression showed that a reduction in bra size was negatively independently associated with breast satisfaction (β = - 18.662, 95%CI: -26.789, -10.535, P < 0.001), while an inferolateral inframammary fold incision was positively independently associated with breast satisfaction (β = 6.430, 95%CI: 0.199, 12.662, P = 0.043). Skin-sparing mastectomy (SSM) (β = 7.468, 95%CI: 0.557-14.308, P = 0.034) and prepectoral implant plane (β = 6.756, 95%CI: 0.278-13.234, P = 0.041) were both positively independently associated with the DRS scores.

Conclusion: Despite the study's limitations, our findings indicate that traditional techniques such as radial incision and inferolateral inframammary fold incision are still prevalent in China. Endoscopic-assisted surgery is associated with superior patient-reported satisfaction, highlighting its potential value for wider dissemination in clinical practice. Factors influencing patient satisfaction include reduced bra cup size, surgical approach, and implant plane.