BMC Cancer最新文献

Background: To investigate the role of the translocase of the outer mitochondrial membrane 40 (TOM40) in oral squamous cell carcinoma (OSCC) with the aim of identifying new biomarkers or potential therapeutic targets.

Methods: TOM40 expression level in OSCC was evaluated using datasets downloaded from The Cancer Genome Atlas (TCGA), as well as clinical data. The correlation between TOM40 expression level and the clinicopathological parameters and survival were analyzed in TCGA. The signaling pathways associated with TOM40 were identified through gene set enrichment analysis. A network of genes co-expressed with TOM40 was constructed and functionally annotated by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The immune infiltration pattern in OSCC was analyzed in the TCGA-OSCC cohort using the CIBERSORT algorithm. Clinically significant factors of OSCC were screened through the expression levels of TOM40 and a clinically relevant nomogram was constructed. The TCGA-OSCC cohort was divided into the TOM40^high and TOM40^low groups and the correlation between TOM40 expression level and the sensitivity to frequently used chemotherapeutic drugs was evaluated. CCK-8 and colony formation assays were applied to determine the cell growth.

Results: TOM40 was highly expressed in OSCC tissues and correlated negatively with the overall survival (P < 0.05). Patients with high TOM40 expression level showed worse prognosis. Furthermore, GO and KEGG enrichment analyses of the differentially expressed genes related to TOM40 showed that these genes are mainly associated with immunity and tumorigenesis. Immunological infiltration analysis has found that the expression levels of TOM40 are correlated with the proportions of several immune cells. Moreover, we found that TOM40 knockdown inhibited cell growth in OSCC cell lines.

Conclusions: Our results uncovered that TOM40 is a reliable prognostic marker and therapeutic target in OSCC.

Background: To assess the utility of the TCGA molecular classification of endometrial cancer in a well-annotated, moderately sized, consecutive cohort of Chinese patients with ovarian clear cell carcinoma (OCCC).

Methods: We performed DNA sequencing on 80 OCCC patients via a panel that contains 520 cancer-related genes. The TCGA molecular subtyping method was utilized for classification. The clinicopathological features were analysed, and the survival correlation was assessed for each subtype.

Results: The most common mutated genes were ARID1A (49%) and PIK3CA (48%). No pathogenic POLE mutations were detected. MSI-high (MSI-H) tumours were observed in 5 (6.3%) patients. A total of 16.3% (13/80) of the patients were classified as the p53 abnormal (p53abn) subtype, and 77.5% (62/80) were classified as the nonspecific molecular profile (NSMP) subtype. All the MSI-H patients had ARID1A mutations, whereas patients with the p53abn subtype had the lowest percentage of ARID1A mutations (27.3%). No significant differences were observed between the molecular subtypes and clinicopathological features. The progression-free survival and overall survival of the entire cohort were closely associated with FIGO stage (p < 0.01), the presence of residual tumour (p < 0.01), and the platinum response (p < 0.01). Molecular classification did not significantly impact prognosis. Univariate analysis revealed that TP53 mutations in advanced-stage (FIGO III-IV) patients were associated with shorter survival.

Conclusions: We did not find prognostic significance of TCGA molecular subtyping in OCCC. POLEmuts are extremely rare, and the incidence of MSI-H and p53abn tumours is also quite low. Further subtyping of the NSMP subgroup is warranted.

Background: Non-small cell lung cancer (NSCLC) is a disease related to inflammation. Proinflammatory cytokines such as interleukin 17 (IL-17) can induce cancer cell proliferation, metastasis and immune escape. Although NSCLC immune escape is partly due to the interaction between PD-1 and PD-L1 and PD-L1 expression can be upregulated in cancer cells upon stimulation with IL-17, the underlying mechanism of IL-17-triggered PD-L1 gene transcription in NSCLC cells remains elusive.

Methods: RT‒PCR, real-time PCR, and IB were used to assess the levels of PD-L1, MEF2C, and TRIM31 in NSCLC tissues as well as in IL-17-stimulated H1299 or PC9 cells. Bioinformatics analysis, luciferase assays, and ChIP were utilized to investigate the transcriptional mechanism of the PD-L1 gene. Co-IP/IB was used to examine the interaction between MEF2C and PD-L1, including MEF2C ubiquitination. IHC staining was carried out to analyse the expression of IL-17RA, MEF2C, TRIM31, and PD-L1 in NSCLC tissue arrays. The corresponding plasmids were constructed and identified. An isograft model was used to verify the findings in vitro.

Results: PD-L1, MEF2C and TRIM31 expression levels were increased in NSCLC tissues and NSCLC cells exposed to IL-17. Mechanistically, MEF2C could bind to the - 778 to -475 nt and - 336 to -97 nt regions of the PD-L1 promoter. TRIM31 could mediate MEF2C K63-linked polyubiquitination at Lys 25, increasing MEF2C recruitment to the PD-L1 promoter and PD-L1 gene transcription. MEF2C, TRIM31 or PD-L1 gene silencing effectively suppressed MEF2C K63-linked polyubiquitination, PD-L1 induction and NSCLC growth in mice inoculated with Lewis lung cancer (LLC) cells transfected with the corresponding shRNA and treated with IL-17.

Conclusion: IL-17 induces PD-L1 gene transcription in NSCLC cells through TRIM31-dependent MEF2C K63-linked polyubiquitination.

Background: Relapsed/refractory classic Hodgkin lymphoma (R/R cHL) remains challenging to treat, and anti-CD30 chimeric antigen receptor T (CAR-T) cell therapy may be effective. This meta-analysis investigates the efficacy and safety of anti-CD30 CAR-T cell therapy for treating R/R cHL.

Methods: A systematic literature search of PubMed, Cochrane, Embase, ClinicalTrials.gov, and Web of Science databases was conducted until February 2024. The odds ratio (OR) with a 95% confidence interval (CI) was analysed using Review Manager 5.4. Outcomes including overall response rate (ORR), complete response (CR), partial response (PR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were extracted for meta-analysis. We used the Methodological Index for Non-Randomized Studies (MINORS) to evaluate the quality of the included literature.

Results: A total of 151 participants from 8 records were included. Meta-analysis showed the ORR of CD30 CAR-T cell therapy for R/R cHL was 57% (95%CI 0.36-0.76, P = 0.50), with a CR of 34% (95%CI 0.13-0.64, P = 0.29) and a PR of 32% (95%CI 0.15-0.55, P = 0.12). With the median follow-up range from 9.5 to 71.5 months, the 1-year PFS was 39% (95% CI 0.30-0.49, P = 0.04), and the 1-year OS was 89% (95% CI 0.65-0.97, P = 0.005). The most common hematologic AE was leukopenia (72%, 95% CI: 0.50-0.87), and the most common non-hematological AE was cytokine release syndrome (CRS) (43%, 95% CI: 0.14-0.76). The grade ≥ 3 AEs was 66% (95%CI 0.06-0.98, I2 = 93%, P = 0.70), 34% (95%CI 0.07-0.78, I2 = 85%, P = 0.51) in neutropenia and thrombocytopenia, respectively. All AEs were tolerable and resolved with treatment.

Conclusion: Current evidence suggests that anti-CD30 CAR-T cell therapy is effective and safe in treating R/R cHL and is worth considering as a viable therapeutic option.

Background: Chemotherapy-induced nausea and/or vomiting (CINV) is an intractable adverse effect of anticancer drugs. Although prophylactic use of fosaprepitant may be effective in reducing CINV, there is a lack of studies evaluating the application of fosaprepitant in real world.

Aims and methods: This study prospectively observed the effectiveness and safety for the prophylaxis of CINV in a real-world clinical setting. A single dose fosaprepitant 150 mg was intravenously administered to enrolled patients 30 min prior to the chemotherapy drug. Initial data were recorded and patients were followed for 120 h (5 days). The primary endpoint is the complete response (CR) rate and the incidence of serious adverse events (SAEs). The second endpoint is the use of rescue therapy. We also performed stratified analyses to investigate the impact of different factors on fosaprepitant for the prevention of CINV in the acute phase.

Results: Between March 2021 to August 2021, 1001 patients were enrolled in this study. CR was 77.32%, 93.61%, and 76.72% for vomiting control in 0-24 h, 24-120 h, and 0-120 h respectively, and 97.4%, 99.1%, and 96.9% for nausea control. No SAEs were recorded. 23.48% or 3.1% of patients needed rescue therapy for vomiting or nausea control respectively, most of which occurred in the acute phase. CR rate decreased with increasing emetogenicity of chemotherapeutic agents.

Conclusions: Single-dose fosaprepitant has shown good performance in real-world clinical practice. This study is the first to prospectively evaluate the efficacy and safety of fosaprepitant for the prevention of CINV in a real-world clinical setting and may be a good complement to the clinical data.

Background: The beneficial role of physical activity for people living with cancer is well established. However, the importance of physical activity to women living with metastatic breast cancer is not known. As motivations and perceptions around physical activity influence behavioural uptake, a qualitative study was undertaken to explore the motivations and perceptions towards physical activity of this group.

Methods: Women living with metastatic breast cancer were recruited through a metropolitan cancer centre in Australia to participate in semi-structured interviews about their physical activity. Open-ended questions explored health-specific factors, goals, barriers, enablers, and interests. Interviews were recorded, transcribed and thematically analysed.

Results: Twenty-three women participated; median age was 60 years (IQR: 20) and median time since metastatic diagnosis was 3.3 years (IQR: 3.0). Twelve women were engaged with physical activity, seven reported intentions to be active but found it challenging, and four reported nominal interest in physical activity. Four categories, covering nine themes, were identified: (i) predispositions towards physical activity, incorporating themes on enjoyment and energy, and positivity and mental resilience; (ii) health-related motivations behind physical activity, incorporating themes on physical and mental health benefits; (iii) social motivations behind physical activity, incorporating themes on enjoying exercise with others, role models and social support, and others' negative perceptions of metastatic breast cancer; and (iv) connections between physical activity and metastatic breast cancer, incorporating themes on prognosis uncertainty, and reframing limiting perceptions.

Conclusions: Participants described a wide-ranging spectrum of experiences and perceptions toward physical activity. Whilst most women perceived improved physical and mental well-being from being physically active, some women were not engaged in being physically active. Behaviour change strategies that target both their attitudes and those around them may address this gap.

Background: Head and neck squamous cell carcinoma (HNSCC), a highly invasive malignancy with a poor prognosis, is one of the most common cancers globally. Circular RNAs (circRNAs) have become key regulators of human malignancies, but further studies are necessary to fully understand their functions and possible causes in HNSCC.

Methods: CircCCT2 expression levels in HNSCC tissues and cells were measured via qPCR. CircCCT2 was characterized by Sanger sequencing, qRT-PCR, RNase R & Actinomycin D treatment, nucleoplasmic separation and FISH experiments. CCK-8 and colony formation assays were performed to determine cell proliferation, and Transwell assays were used to determine migration and invasion. A xenograft tumor model was used to study the influence of circCCT2 on HNSCC in vivo. Dual-luciferase gene reporter, RIP, western blotting, and rescue experiments, were used to explore target-binding relationships and regulatory mechanisms.

Results: CircCCT2 was significantly upregulated in HNSCC tissues and cells. High circCCT2 levels were associated with advanced T stage, N stage, clinical stage and poor prognosis. Functionally, we verified that circCCT2 promotes HNSCC development in vitro and in vivo. Mechanistically, functioning as a competitive endogenous RNA (ceRNA) or miRNA sponge, circCCT2 binds directly to miR-146a-5p and increases interleukin-1 receptor-associated kinase 1 (IRAK1) levels, which enhances the malignant development of HNSCC by driving epithelial-mesenchymal transition (EMT).

Conclusion: CircCCT2 promotes HNSCC development through the miR-146a-5p/IRAK1 axis, revealing that circCCT2 is a potential biomarker and target for HNSCC.

Purpose: To evaluate the prognostic significance of progesterone receptor (PR) expression and the PIK3CA mutation status in HR+/HER2 - breast cancer patients, with the goal of screening patients who may derive the greatest benefit from PI3K-targeted therapy.

Methods: A retrospective analysis was conducted on 152 HR+/HER2 - breast cancer patients stratified by PR expression levels and PIK3CA mutation status. The study population was divided into groups on the basis of a median PR threshold of 50% and further subdivided by PIK3CA mutation status. To evaluate the variability of clinicopathologic features among these groups, t tests and ANOVA were employed. The influence of these variables on survival was analyzed via Cox regression. Additionally, a risk prediction model was developed using the PR expression level and PIK3CA mutation status. The prognostic utility of this model was examined via both Kaplan‒Meier (KM) survival curves and receiver operating characteristic (ROC) analyses. These methods have also been utilized to explore the associations between clinicopathologic parameters and clinical outcomes with respect to survival prediction and prognosis.

Results: Significant differences in age, ER expression, and Ki67, HER2, and PIK3CA mutation status were detected between the groups (P < 0.05). Specifically, elevated PR expression was correlated with lower levels of Ki67 and low HER2 expression. The presence of a PIK3CA mutation was significantly linked to survival outcomes according to both univariate and multivariate Cox regression analyses. Moreover, ROC analysis revealed that models incorporating both PR expression and PIK3CA mutation status achieved the highest level of diagnostic precision (AUC = 0.82).

Conclusion: PR expression and PIK3CA mutation status are significant prognostic markers in HR+/HER2 - breast cancer patients. Assessing these biomarkers in combination can enhance prognostic stratification, potentially guiding more informed clinical decision-making.