BMC Cancer最新文献

Background: Aberrant expression of N3-methylcytidine methyltransferase 2B (METTL2B) has been observed in various human malignancies, including those of the prostate, liver, breasts, and bladder. However, its role in ovarian cancer (OC) remains largely unexplored. This research preliminarily investigated METTL2B expression in OC and elucidated the associated molecular mechanisms.

Methods: We utilized three publicly available cancer-related databases (Genotype-Tissue Expression, Gene Expression Omnibus, and The Cancer Genome Atlas) to identify gene signatures in patients with OC and normal individuals with a specific focus on METTL2B. The role of METTL2B in OC was evaluated using patient survival data, and its impact on oncogenic behaviors in both cell and animal models, including growth potential, migration, invasion, and the tumor microenvironment, was examined. This assessment was conducted using bioinformatics tools such as Gene Set Cancer Analysis, GeneMANIA, and Tumor Immune Single-cell Hub 2. Additionally, the association between drug sensitivity and METTL2B expression was analyzed using CellMiner.

Results: METTL2B expression was significantly elevated in OC, highlighting its potential clinical value in the diagnosis and prognosis of OC. Patients with lower METTL2B expression exhibited favorable survival. Furthermore, METTL2B knockdown significantly disrupted oncogenic behaviors in OC cell lines by suppressing the mTOR/AKT signaling pathway. Additionally, bioinformatics-based Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses suggested a close correlation between METTL2B and immune responses.

Conclusions: Our research confirmed the upregulation of METTL2B in OC, suggesting its oncogenic function. However, METTL2B expression was negatively correlated with the infiltration scores of multiple immune cells, including cytotoxic cells and T cells, indicating its complex role in the tumor immune microenvironment. These findings highlight the significant clinical value of METTL2B in the diagnosis and prognosis of OC.

Background: Cancer survivors face many challenges in long-term health management, including malnutrition, systemic inflammation, and sleep issues, which significantly affect their survival and quality of life.

Methods: A prospective cohort study was derived from the National Health and Nutrition Examination Survey from 2005-2018 harboring 1,908 cancer survivors (weighted population, 11,453,293), of whom 688 deaths (220 from cancer mortality, 468 from non-cancer mortality). The Advanced Lung Cancer Inflammation Index (ALI) was used as a measure of nutritional status and systemic inflammation in cancer patients. Weighted multivariable Cox proportional hazards regression models were utilized to explore the independent and combined effects of ALI and sleep quality on mortality outcomes.

Results: The participants with a high ALI were more likely to be female, aged 40 to 64 years, non-Hispanic white, and have a higher BMI. We observed that elevated ALI levels were associated with decreased risks of all-cause mortality (Hazard ratio [HR] = 0.601, 95% Confidence interval [CI] = 0.521-0.695, P < 0.001), cancer-specific mortality (HR = 0.659, 95% CI = 0.497-0.870, P = 3.34 × 10^-3) and non-cancer-specific mortality (HR = 0.579, 95% CI = 0.478-0.701, P < 0.001). Similarly, better sleep quality (e.g., without sleep troubles) was associated with lower risks of all-cause mortality (HR = 0.761, 95% CI = 0.620-0.933, P = 8.79 × 10^-3) and non-cancer-specific mortality (HR = 0.713, 95% CI = 0.572-0.890, P = 2.80 × 10^-3). Notably, the joint analysis showed that cancer survivors with higher ALI levels and better sleep quality (e.g., standard sleep duration) had the lowest risks of all-cause (HR = 0.468, 95% CI = 0.352-0.622, P < 0.001), cancer-specific mortality (HR = 0.631, 95% CI = 0.333-0.672, P = 7.59 × 10^-3) and non-cancer-specific mortality (HR = 0.440, 95% CI = 0.315-0.615, P < 0.001).

Conclusions: This study suggests that better nutritional and inflammatory status, combined with good sleep quality, may contribute to improved survival among cancer survivors. These results underscore the potential clinical importance of integrating nutritional and sleep quality assessments into the long-term care of cancer survivors to enhance their overall prognosis.

Background: Research on the antinuclear antibodies (ANA) profile across different pathological subtypes of lymphoma was limited. Our study aimed to assess ANA profile and investigate its potential prognostic value in lymphoma.

Method: We collected plasma samples from 139 lymphoma patients and analyzed the expression of plasma ANA, SSA, and SSB using the enzyme-linked immunosorbent assay (ELISA). Additionally, we focused on B-cell non-Hodgldn's lymphoma (B-NHL) for survival analysis.

Results: Influencing factors for ANA profile levels included age (ANA: P = 0.0035, SSA: P = 0.0553, SSB: P = 0.0025), gender (SSA: P = 0.0436), serum IgG (ANA, P = 0.0385; SSA, P = 0.0175; SSB, P = 0.0291), and erythrocyte sedimentation rate (ESR) (SSA: P = 0.0380). In subtype comparisons, ANA and SSB levels were significantly lower in low-grade B-NHL compared to Hodgkin lymphoma (HL) (low-grade B-NHL vs. NHL: ANA, P = 0.0107; SSB, P = 0.0126). Aggressive NHL exhibited a higher ANA profile compared to indolent NHL (aggressive NHL vs. indolent NHL: ANA, P = 0.0262; SSA, P = 0.0136; SSB, P = 0.0280). Kaplan-Meier analyses identified SSA and SSB as potential prognostic biomarkers in patients with B-NHL undergoing chemotherapy.

Conclusion: Our study evaluated ANA profile in various subtypes of lymphoma and demonstrated the prognostic value of autoantibodies in predicting clinical outcomes. The results highlight the potential of incorporating ANA profile into the prognostic assessment of lymphoma.

Background: With the rising prevalence of abdominal radical hysterectomy, the need for perioperative blood transfusion has emerged as a significant clinical challenge. Independent risk factors for blood transfusion during abdominal radical hysterectomy remains limited, and identifying these factors is needed.

Methods: A retrospective analysis of data was performed using the Nationwide Inpatient Sample (NIS), focusing on patients who underwent abdominal radical hysterectomy between 2010 and 2019. Patients were categorized into two groups based on whether they received a blood transfusion. The analysis encompassed various demographic factors, including race, sex, and age, as well as length of stay (LOS), total hospitalization charges, hospital characteristics (admission type, insurance type, bed size, teaching status, geographic location, and hospital region), hospital mortality rates, comorbidities, and perioperative complications. Subsequently, both univariate and multivariate logistic regression analyses were employed to ascertain factors associated with abdominal radical hysterectomy patients requiring blood transfusions.

Results: Blood transfusions occurred in 14.84% of patients between 2010 and 2019, with a downward trend over time. Receiving a transfusion was associated with several negative outcomes, including a longer length of stay, higher total charges, and complications like thrombocytopenia, acute myocardial infarction, pneumonia, and so on. Additionally, patients who received transfusions were more likely to experience postoperative delirium, deep vein thrombosis, and wound infection. Independent risk factors for blood transfusion include Black race, Asian or Pacific Islander race, non-elective surgery, hospitalization in a rural setting, pre-existing medical conditions like coagulopathy, chronic blood loss anemia, deficiency anemia and others. Conversely, patients with private insurance, residing in the West, or Midwest/North Central regions were less likely to require a blood transfusion.

Conclusion: Our study highlights the concern of perioperative blood transfusion in radical hysterectomy, linked to significant complications. Reducing intraoperative blood loss and optimizing care based on patient factors are crucial for improving outcomes.

Background: This study investigated the optimal timing of concurrent chemoradiotherapy (CCRT) following surgery for patients with newly diagnosed glioblastoma (GBM). The focus was on understanding whether the interval between surgery and CCRT impacts survival outcomes.

Methods: Data from the Korean National Health Insurance Research Database ( https://opendata.hira.or.kr/ ) were collected to retrospectively review 3,586 patients diagnosed with GBM in South Korea between 2008 and 2021. Patients were divided into early CCRT (≤ 21 days between surgery and CCRT) and late CCRT (> 21 days between surgery and CCRT) groups and further categorised based on the type of surgery (biopsy alone or surgical resection). The study estimated overall survival (OS) and conducted univariable and multivariable Cox regression analyses.

Results: The median overall survival (OS) for the entire cohort was 19.98 months (95% Confidence Interval [CI]: 19.12-20.86 months). In univariable analysis, the late CCRT group demonstrated a longer median OS compared to the early CCRT group (20.47 vs. 17.94 months, P = 0.0002, log-rank test). However, this difference was not significant in multivariable analysis (Hazard Ratio [HR] = 0.98, 95% CI: 0.782-1.091, P = 0.6663). Subgroup analysis revealed that late CCRT was associated with prolonged OS in patients who underwent surgical resection (adjusted HR = 0.85, 95% CI: 0.752-0.955, P = 0.0065), whereas in the biopsy-alone group, late CCRT was associated with shorter OS (adjusted HR = 1.80, 95% CI: 1.378-2.346, P < 0.0001).

Conclusions: Patients who initiated CCRT more than 21 days post-resection demonstrated improved overall survival (OS) compared to those who began CCRT earlier. In contrast, among patients who underwent biopsy alone, initiating CCRT within 21 days was associated with better outcomes. These findings suggest that the optimal timing for CCRT initiation in GBM may depend on the extent of residual tumour.

Purpose: Dietary factors might contribute to the risk of lung cancer by increasing the concentration of inflammatory markers. The literature-derived Dietary Inflammatory Index (DII) has been established to evaluate the inflammatory potential of diet correlated with inflammatory markers. The association between DII scores and the risk of lung cancer has been conflicting. So, in the current study, we aimed to assess the effect of pro-inflammatory dietary patterns measured with DII and the risk of lung cancer.

Methods: A multi-center case-control study was carried out on 616 patients with lung cancer and 3412 healthy controls. Dietary intakes were collected using a 131-item food frequency questionnaire during a face-to-face interview. The DII scores including thirty-six nutrients were calculated after energy adjustments. Finally, the association between DII level and the risk of lung cancer was evaluated by performing a multi-variable regression method after adjusting for potential confounders.

Results: The risk of overall lung cancer, small cell, and squamous cell carcinoma was elevated in the third tertile compared to the first tertile of the DII score, (odds ratio [OR] _{T3 vs. T1} of overall lung cancer = 1.38 (95% confidence interval [CI] 1.08-1.77), P trend = 0.01, OR _{T3 vs. T1} of squamous cell lung cancer = 1.82 (95% CI 1.02-3.24), P trend = 0.04, OR _{T3 vs. T1} of small cell lung cancer = 1.66 (95% CI 1.08-2.54), P trend = 0.019). However, no increase was observed in the risk of adenocarcinoma by adherence to a pro-inflammatory dietary pattern.

Conclusion: A positive link was found between DII and the risk of overall lung cancer, small-cell, and squamous-cell lung cancer. However, there was no association between DII and the risk of lung adenocarcinoma.

Background: Today the prerequisites exist to initiate risk-stratified screening according to a woman's individual risk of breast cancer as opposed to existing one-size-fits-all age-based programmes. This presupposes that the women accept having their personal risk score estimated and their screening intervals changed accordingly. Risk-stratified screening has not yet been implemented in any country, but in the future many European countries will very likely move towards more personalized screening.

Methods: This qualitative study among 46 women aged 50-69 years used an anthropological approach and interpretive description. Data was collected using semi-structured focus group interviews and telephone interviews. The interviews were analysed using systematic text condensation.

Objective: The aim of this study was to explore Danish women's understanding of breast cancer risk and their attitudes towards the concept of risk-stratified breast cancer screening.

Results: The women highly valued the current screening program, seeing regular mammograms as crucial for early detection. The women had good knowledge of the causes of breast cancer, but they had not given much thought to their own risk. They found a personalized screening approach more reliable than age-based screening, understanding that low risk is not the same as no risk just as high risk is not equal to ever developing breast cancer. Despite concerns about increased anxiety arising from knowing one's risk, they appreciated the possibility of more frequent screenings for high-risk individuals.

Conclusion: In general, the women showed acceptance of a new breast cancer screening concept estimating their personal risk score. Due to concerns about interval cancers and the prolonged screening intervals for women at low risk, offering more intensified screening for high-risk women may be less challenging than deescalating screening for low-risk women. Whether the expressed positive attitude and curious interest will translate into actual participation if implemented, remains to be investigated further in an ongoing Danish trial.

Background: Patients with light-chain (AL) amyloidosis and concomitant multiple myeloma (MM) are known to have a worse prognosis, while the prognostic implication of cytogenetic abnormalities (CA) and optimal treatment schemes are not well-established. By comparing patients with MM or AL amyloidosis (AL) alone, this study aimed to evaluate the clinical characteristics, CA, and outcomes of patients with AL amyloidosis and concomitant symptomatic MM (MM-AL) and sought to provide evidence for their management.

Methods: In total, 915 consecutive patients with newly diagnosed AL amyloidosis or MM were retrospectively analyzed. Patients were classified as MM-alone, MM-AL or AL-alone. The presence of symptomatic MM was based on the International Myeloma Working Group criteria, and the diagnosis of AL amyloidosis was confirmed by Congo-red-positive biopsy and immunoelectron microscopy.

Results: Of 915 patients, 658, 106, and 151 were in the MM-alone group, MM-AL group, and AL-alone group, respectively. The three groups shared a similar incidence rate of CA, while the prevalence of t(11;14) was significantly higher in the AL-alone group than in the MM-AL and MM-alone group (40.7% vs. 25.7% vs. 16.6%, p < 0.001), and the prevalence of del13q, gain1q21 and high-risk CA (HRCA) decrease in turn in MM-alone, MM-AL and AL-alone group (del13q, 46.5% vs. 39.4% vs. 28.5%, p < 0.001; gain1q21, 52.6% vs. 45.2% vs. 27.3%, p < 0.001; HRCA, 27.5% vs. 16.0 vs. 7.3%, p < 0.001). The progression-free survival (PFS) and overall survival (OS) of MM-AL patients (median, 12.8, and 25.2 months) were significantly inferior to patients with MM-alone and AL-alone. No significant difference in PFS and OS was found between MM-AL patients with and without HRCA. When stratified by the type of plasma cell disease and status of t(11;14), patients with MM-AL and t(11;14) presented the worst OS (median, 8.2 months, p < 0.001). Regarding the management of MM-AL, extended cycles of induction therapy and the use of maintenance therapy contributed to a better prognosis.

Conclusions: There was an apparent discrepancy in the distribution and prognostic implication of CA among different plasma cell diseases. Patients with MM-AL had the worst clinical outcomes, requiring extended duration of induction therapy and maintenance therapy.

Background: Extrachromosomal circular DNA (eccDNA), a novel class of DNA with a circular topological structure, is present in a variety of cancer cells and tissues and may play broad roles in processes ranging from aging to cancer cell heterogeneity through multiple mechanisms. EccDNA has been characterized by profile, structure and function in several prominent studies but its effect on hydroquinone (HQ)-induced malignantly transformed cells (TK6-HQ) is still elusive.

Methods: Circle-seq was applied to determine the eccDNA counts and characteristics of TK6-HQ cells. DNA-fluorescence in situ hybridization was used to measure the abundance of eccDNA_DTX1. Differential gene expression analysis was carried out by RNA-seq. Gene expression was quantified by wertern blot and qPCR. Decircularization of eccDNA_DTX1 was achieved by CRISPR/Cas9. Tumorigenicity was evaluated by xenograft assay in BALB/c nude mice.

Results: In this study, we characterized the structure of eccDNAs and the function of DTX1-containing eccDNA (eccDNA_DTX1) in TK6-HQ cells. A total of 669,179 eccDNAs were identified, including 901 eccDNAs with different counts. Most of the eccDNAs were < 1000 bp in length and were enriched in four periodic peaks starting at 186 bp with an interval of ~ 180 bp. The genomic distribution of eccDNAs confirmed that eccDNAs could be observed across all chromosomes and had greater enrichment on chromosomes 17, 19, 20, and 22, with abundant Alu repeat elements, introns and CpG islands. By combining the results of the integrated circle-seq analysis of eccDNAs with those from the RNA-seq analysis (differentially expressed genes, 1064 upregulated and 427 downregulated), the authors showed that the transcription of 20 potential coding genes might be driven by eccDNAs. Finally, the knockdown of eccDNA_DTX1 by CRISPR/Cas9 inhibited the growth of TK6-HQ cells in vitro and in vivo by inhibiting the transcription of DTX1 and promoting ferroptosis, and ferroptosis inhibior, Ferrostatin-1, abrogated the proliferation inhibition of eccDNA_DTX1 knockdown.

Conclusions: EccDNA_DTX1 promotes cell growth in hydroquinone-induced malignantly transformed cells by regulating the transcription of DTX1 and ferroptosis. This study profiles eccDNA characteristics and defines the role and mechanism of eccDNA_DTX1 for the first time, shedding new light on the relationship between eccDNAs and carcinogenesis.

Background: Appropriate immobilization setup for postmastectomy radiotherapy may help to improve tumor control and to reduce radiation-related toxicities. This study aims at retrospectively evaluate the outcome and toxicities of postmastectomy radiotherapy (PMRT) with a novel integral cervicothoracic thermoplastic mask strategy.

Methods: Breast cancer patients were treated with modified radical mastectomy and PMRT. Patient immobilization setup was performed with the placement of a 1-cm thickened wax film on the ipsilateral chest wall and an integral cervicothoracic thermoplastic mask. PMRT was delivered according to the institutional protocol. Dose distribution, disease control, patient survival and radiation-induced toxicities were evaluated.

Results: Four-hundred nineteen eligible patients with complete follow-up information were included in the final analysis. The median follow-up was 40.2 (95%CI: 38.9-41.6) months. Two (0.5%) patients had local recurrence and 48 (11.4%) patients had distant metastasis. There were 22 (5.3%) deaths from all causes, of which 19 were caused by breast cancer. The 3-year overall survival (OS) rate was 94.8%. ER status, PR status, triple negative status, and T stages were significantly related to patient survival (p < 0.05). HER2 expression, N stage were not significantly related to patient survival. Most common radiation-induced toxicities included grade I (87.6%) and grade II (10.2%) dermatitis, and grade I pneumonitis (28.9%) found by chest X-ray or CT scans. No clinical detectable cardiovascular event related to radiotherapy was identified.

Conclusion: Postmastectomy radiotherapy with integral cervicothoracic thermoplastic mask leads to favorable outcome and moderate toxicities compared with results reported in literature and might be of clinical significance in breast cancer patient. However, this approach has not been compared directly with postmastectomy radiotherapy without immobilization, and its applicability in other regions with different treatment protocols requires further investigation.