BMC Cancer最新文献

The intricate regulatory roles of small non-coding RNAs (sncRNAs), including PIWI-interacting RNAs (piRNAs) and microRNAs (miRNAs), have been increasingly recognized in the modulation of cellular functions and are associated with the pathogenesis of various diseases, notably cancer. However, the specific dysregulation patterns of sncRNAs in non-muscle-invasive bladder cancer (NMIBC) have yet to be fully delineated, highlighting a significant gap in our current understanding. To elucidate the expressional dynamics of sncRNAs for patients with NMIBC, we characterized the profile of piRNAs and miRNAs by next-generation sequencing. We identified the differentially expressed sncRNAs between tumor and paracancerous tissues and characterized their distribution along the genome. We further revealed a set of immune-related piRNAs and dysregulated miRNAs that might be associated with NMIBC pathogenesis. Differentially expressed piRNAs were predominantly localized at the long arms of chromosomes 13, 1, and 6. Notably, the targets of specific piRNAs, including piR-hsa-2215234, piR-hsa-105306, piR-hsa-102066, and piR-hsa-236465, show significant associated with antigen processing and presentation pathway. Additionally, differentially expressed miRNAs are mainly located on chromosome 14 and their target genes tend to be involved in cancer-related pathways, suggesting their potential regulatory roles in NMIBC. Collectively, this study revealed the global sncRNA dysregulation in NMIBC, and the identified sncRNAs are implicated in the modulation of both immune and cancer pathways, suggesting their contribution to the pathogenesis and potential targets for immunotherapy.

Background: The prognostic significance of long non-coding RNA LINC00657 remains ambiguous, and its role in prostate cancer (PCa) is not well characterized. This study aims to conduct a meta-analysis to clarify the clinical implications of LINC00657 in various malignancies and to assess its impact on PCa.

Methods: A systematic search was conducted across PubMed, Embase, and Web of Science to identify relevant studies. Hazard ratios (HR) with 95% confidence intervals (95% CI) and associated clinicopathological factors were extracted. Subgroup analyses were performed based on sample size and cancer type. The expression levels of LINC00657 in PCa tissues were analyzed using the GTEx and TCGA databases. Additionally, transwell, wound healing, and EdU assays were utilized to evaluate cell migration and proliferation. An in vivo xenograft model was also employed to investigate the role of LINC00657 in PCa.

Results: The meta-analysis included 11 eligible studies comprising 1,226 patients. Our findings indicate that overexpression of LINC00657 is significantly correlated with poor overall survival (HR = 2.09, 95% CI: 1.26-2.91), distant metastasis (OR = 2.15, 95% CI: 1.34-3.46), and advanced TNM staging (OR = 3.07, 95% CI: 1.22-7.74) across malignancies. Analysis of the TCGA and GTEx databases, corroborated by experiments in cell lines, revealed that LINC00657 is overexpressed in PCa. Furthermore, knockdown of LINC00657 resulted in reduced migration and invasion of PCa cells in vitro, as well as inhibited cell growth both in vitro and in vivo.

Conclusion: The findings suggest that LINC00657 plays an oncogenic role in PCa and could be a valuable indicator of poor prognosis in cancer.

Objectives: This study aimed to assess the effectiveness and safety of conventional transarterial chemoembolization (c-TACE) followed by irreversible electroporation (IRE) for the treatment of hepatocellular carcinoma (HCC).

Methods: From January 2019 to September 2019, 12 patients with HCC who received c-TACE followed by IRE comprised the study group. The control group comprised 15 patients who received c-TACE followed by radiofrequency ablation (RFA). The 1-month, 3-month, 6-month, and 12-month local control rates and median progression-free survival (PFS) were compared between the two groups. Additionally, postoperative complications were assessed.

Results: The study group comprised 12 patients (median age: 57.5 years; range: 46-68 years), while the control group consisted of 15 patients (median age: 56 years; range: 31-69 years). Local control rates at 1, 3, 6, and 12 months were 91.7%, 91.7%, 83.3%, and 33.3%, respectively, for the study group, and 73.3%, 66.7%, 66.7%, and 20.0% for the control group. Statistical analysis revealed no significant differences between the two groups. In terms of survival, 9 patients (75%) in the study group and 11 patients (73.3%) in the control group were still alive at the last follow-up. The median PFS was 8 months in the study group and 7 months in the control group, with no significant difference between the two groups (p = 0.96). Notably, no severe surgery-related side effects were observed in either group, and also no significant differences were found in postoperative complications between the two groups (p = 0.64).

Conclusions: The long-term therapeutic outcomes of c-TACE followed by IRE were found to be similar to those of c-TACE followed by RFA in the study. The research suggests that c-TACE followed by IRE offered an effective and safe treatment option for HCC.

Background: Triglyceride-Glucose (TyG) index, a novel surrogate marker for insulin resistance, has been linked to the risk of various cancers, such as breast and colorectal cancers. However, the relationship between the TyG index and its related indices with the risk of pancreatic cancer(PC) remains unclear.

Methods: This large-scale, prospective cohort study utilized data from the UK Biobank, involving 428,152 participants who were free of PC at baseline. The primary outcome was incident PC. To evaluate the relationships between TyG-related indices and PC onset, covariate-adjusted Cox proportional hazards regression models and restricted cubic spline (RCS) analyses were employed. Additionally, we explored the relationships between TyG-related indices and incident PC within subgroups defined by age, gender, diabetes, hypertension, pancreatitis history, smoking status, and drinking status. Sensitivity analyses were conducted to confirm the robustness of our findings.

Results: Over an average follow-up period of 13.8 years, a total of 1,759 PC cases occurred. The risk of developing PC increased with higher levels of TyG-related indices. RCS curves illustrated a linear positive relationship between TyG-related indices and incident PC. Subgroup analyses indicated that the relationships between the TyG index, TyG-waist circumference, and TyG-waist-to-hip ratio and PC risk were more pronounced in participants without hypertension, without pancreatitis history, and those with drinking history (P for interaction < 0.05). Sensitivity analyses further validated the robustness of these findings.

Conclusions: TyG-related indices were independently related with a higher risk of incident PC, highlighting the importance of incorporating these indices into PC risk assessment tools and provides strong support for constructing a more comprehensive PC risk assessment framework.

Background: Colorectal cancer with liver metastasis affects both men and women. However, therapeutic strategies and long-term outcomes could be influenced by patients' sex, due to variations in tumour biology, lifestyle, and dietary habits. By conducting a comprehensive comparative analysis, this study aims to detail differences in tumour characteristics, postoperative complications, recurrence rates, and survival outcomes between sexes.

Methods: Single-centre retrospective analysis between 2010 and 2022 of all patients undergoing liver surgery for colorectal liver metastases (CRLM) at the Department of Surgery, Charité- Universitätsmedizin Berlin. Patients were stratified by sex. Statistical analysis was performed using RV4.2.

Results: We analysed 642 patients who underwent hepatic resections for CRLM. Baseline patient characteristics were comparable between sexes: However, significant differences (p < 0.001) were noted in body mass index (BMI), with females exhibiting lower BMIs (median BMI in females: 23.7 kg/m² vs. males: 26.5 kg/m²). Primary tumour locations varied significantly (p = 0.008), with females presenting more sigmoid colon tumours (37%), while males predominantly had rectal tumours (35%). RAS mutation rates were higher in females (54%) than males (34%, p = 0.005). A higher prevalence of bilobar metastases were evident in men (62%, p = 0.011), yet surgical techniques and complications showed comparable distributions. The time for resection was longer in males (median 304 min vs. 290 min in females); however, conversion to open surgery took place more often in females (5.2% vs. 2.3% in males). Postoperative complications and survival rates showed no significant differences by patients' sex.

Conclusion: Distinct sex-related patterns in tumour characteristics and postoperative outcomes in patients with CRLM were observed, emphasizing the need for further investigations to understand and address gender-based disparities for more personalized clinical management in the future.

Trial registration: This research was conducted with ethical approval from the relevant institutional review board Ethikkommission der Charité- Universitätsmedizin Berlin' (reference numbers EA2/006/16 and EA4/084/17). No other registration applied.

Background: Previous studies have indicated that clinical and imaging features may assist in distinguishing between benign and malignant solid lung nodules. Yet, the specific characteristics in question continue to be debated. This meta-analysis aims to identify risk factors for malignant solid lung nodules, thereby supporting informed clinical decision-making.

Methods: A comprehensive search of databases including PubMed, Embase, Web of Science, Cochrane Library, Scopus, Wanfang, CNKI, VIP, and CBM was conducted up to October 6, 2024. Only publications in Chinese or English were considered. Data analysis was performed using Stata 16.0 software.

Results: This analysis included 32 studies, comprising 7758 solid pulmonary nodules, of which 3359 were benign and 4399 were malignant. It was found that the incidence of spiculate signs in malignant solid pulmonary nodules (MSPN) was higher than in benign solid pulmonary nodules (BSPN) [OR = 3.06, 95% CI (2.35, 3.98), P < 0.05. Additionally, increases were observed in the incidences of vascular convergence[OR = 16.57, 95% CI (8.79, 31.24), P < 0.05], lobulated signs [OR = 5.17, 95% CI (3.83, 6.98)], air bronchogram sign[OR = 2.96, 95% CI (1.62, 5.41), P < 0.05], pleura traction sign [OR = 2.33, 95% CI (1.65, 3.29), P < 0.05], border blur [OR = 2.94, 95% CI (1.47, 5.85), P < 0.05], vacuole signs [OR = 5.25, 95% CI (2.66, 10.37), P < 0.05], and family history of cancer [OR = 3.85, 95% CI (2.43, 6.12), P < 0.05] compared to BSPN. Older age[OR = 1.06, 95% CI (1.04, 1.07), P < 0.05], higher prevalence in females [OR = 2.98, 95% CI (2.27, 3.92), P < 0.05], larger nodule diameters [OR = 1.25, 95% CI (1.13, 1.38), P < 0.05], and lower incidence of calcification [OR = 0.21, 95% CI (0.10, 0.48), P < 0.05] were also associated with MSPN. No significant differences were found between MSPN and BSPN regarding CEA and emphysema (all P > 0.05).

Conclusions: This meta-analysis highlights that spiculate sign, vascular convergence sign, lobulated sign, diameter, border blur, vacuole sign, age, gender, family history of cancer, pleura traction, air bronchogram sign, and calcification are significant markers for predicting malignancy in SPNs, potentially influencing clinical management. However, further well-designed, large-scale studies are needed to confirm these findings.

Background: The incidence of early-onset breast cancer (< 50 years) has been increasing over the past decades with the role of modifiable, lifestyle-related risk factors remaining mostly unidentified.

Methods: To investigate the role of key lifestyle factors in the incidence trends of early-onset breast cancer (EOBC), we pooled data from six health studies in Finland in 1972-2015 and combined them with breast cancer data from the Finnish Cancer Registry. The cohort consisted of 56,253 women with 397 EOBCs. The effects of risk factors (hazard ratios) on EOBC and average annual percent change (AAPC) of incidence were estimated using Poisson regression models.

Results: The highest annual increase in age-standardized incidence was observed among women aged 40-49 who were overweight (AAPC 4.0%, 95% CI 0.5-7.7%), currently smoking (AAPC 3.3%, 95% CI 0.1-6.6%) or moderately physically active (AAPC 2.9%, 95% CI 0.3-5.6%).

Conclusions: The increase in early-onset breast cancer incidence was highest among women aged 40-49 who were overweight, currently smoking, or moderately physically active, while no change by risk factors was found in women under 40 years of age. Our findings suggest a different type of cancer process in young adults and highlight the importance of lifestyle risk factors in the incidence of EOBC.

Objective: The interaction between T cells, particularly naïve CD4 T cells (CD4Tn), and colorectal cancer (CRC) is highly complex. CD4Tn play a crucial role in modulating immune responses within the tumor microenvironment, yet the precise mechanisms by which they influence tumor progression remain elusive. This study aims to explore the relationship between CRC and CD4Tn, identify biomarkers and therapeutic targets, and focus on the role of CD4Tn in shaping the immune environment of CRC.

Methods: Single-cell transcriptomics, alongside the scPagwas algorithm, were employed to identify pivotal T cell subsets involved in CRC progression. Bulk transcriptomic data were further analyzed using deconvolution algorithms to elucidate the roles of these key T cell subsets. The abundance of naïve CD4 T cells (CD4Tn) was specifically assessed to gauge patient responses to immunotherapy, alterations in the immune microenvironment, and correlations with genetic mutations. Key genes linked to CD4Tn were identified using weighted gene co-expression network analysis and Pearson correlation scores. The SMR algorithm was subsequently used for validation, with experimental verification following.

Results: Through single-cell transcriptomics and the scPagwas algorithm, CD4Tn was confirmed as a critical cell type in CRC progression. High infiltration of CD4Tn cells in CRC patients was correlated with poorer prognosis and suboptimal responses to immunotherapy. SMR analysis suggested a potential causal link between DRAM2 gene expression and CRC progression. Experimental knockdown of DRAM2 in colorectal cancer cells significantly inhibited tumor growth.

Conclusion: The DRAM2 gene, associated with CD4Tn cells, appears to play a pivotal role in the advancement of CRC and may represent a promising therapeutic target for treatment.

Background: Lysine acetylation is a critical post-translational modification regulating tumor initiation and progression. Lysine acetyltransferase 7 (KAT7)-mediated lysine acetylation is frequently dysregulated in cancer. However, the role of KAT7-mediated lysine acetylation in hepatocellular carcinoma (HCC) progression remains unclear.

Methods: Bioinformatic analysis was used to investigate the expression, clinicopathological characteristics and diagnostic prognostic value of KAT7 in HCC. CCK-8 assays, colony-forming assays, apoptosis assays and nude mouse xenograft models were utilized to detect the oncogenic functions of KAT7 in HCC. Immunoprecipitation (IP) assay and mass spectrometry (MS) analysis were performed to identify the KAT7-binding protein Y-box binding protein 1 (YBX1). Transcriptome sequencing and functional enrichment analysis were employed to elucidate the downstream pathway regulated by KAT7 and YBX1. Chromatin immunoprecipitation (ChIP) assay was used to evaluate YBX1 binding to the promoter regions of ribonucleotide reductase regulatory subunit M2 (RRM2) and thymidine kinase 1 (TK1). Weighted gene co-expression network analysis and selection operator regression analysis were used to build risk prediction models.

Results: This study demonstrated that elevated KAT7 expression is associated with poor prognosis in HCC patients. Knockdown of endogenous KAT7 in HCC cells attenuated tumorigenic phenotypes associated with cell proliferation, colony formation and orthotopic xenograft tumor growth, indicating a pro-tumorigenic role of KAT7 in HCC. YBX1 was identified as a novel non-histone substrate for KAT7, and the E508 residue of KAT7 is essential for binding. Following the functional enrichment analysis, KAT7 and YBX1 were correlated with nucleotide metabolism. Furthermore, KAT7 binds to YBX1 and modulates its post-translational expression, which enhances the transcriptional activity of the central nucleotide metabolism enzymes RRM2 and TK1. Additionally, we constructed a novel prognostic prediction model based on KAT7, YBX1, RRM2 and TK1, which validated the predictive accuracy and prognostic value of KAT7-mediated acetylation is consistent with clinical outcomes in HCC.

Conclusions: Our findings highlight that KAT7 acetylates YBX1 and promotes HCC progression by reprogramming nucleotide metabolism, offering therapeutic implications.