BMC Cancer最新文献

Immune cells are pivotal components in the tumor microenvironment (TME), which can interact with tumor cells and significantly influence cancer progression and therapeutic outcomes. Therefore, classifying cancer patients based on the status of immune cells within the TME is increasingly recognized as an effective approach to identify prognostic biomarkers, paving the way for more effective and personalized cancer treatments. Considering the high incidence and mortality of colorectal cancer (CRC), in this study, an integrated machine learning survival framework incorporating 93 different algorithmic combinations was utilized to determine the optimal strategy for developing an immune-related prognostic signature (IRPS) based on the average C-index across the four CRC cohorts. Notably, IRPS was demonstrated to be an independent risk factor for predicting the survival outcomes of CRC patients, showing superior performance compared to traditional clinical features and 63 published signatures in both training and validation cohorts. Furthermore, CRC patients classified in the low-risk group according to the IRPS showed higher sensitivity to immunotherapy than those in the high-risk group, suggesting that low-risk patients are more likely to benefit from immunotherapy. Through in silico screening of potential compounds, dasatinib, vinblastine, and YM-155 were identified as potential therapeutic agents for high-risk CRC patients. In vitro studies demonstrated that knockdown of APCDD1, a key component of the IRPS, inhibited the proliferation, migration and invasion of HT-29 cells and promoted their apoptosis. Thus, the IRPS serve as a powerful tool for predicting patient prognosis, immunotherapy response and candidate drugs, thereby enhancing clinical decision-making and treatment evaluation of CRC.

Background: Women living with metastatic breast cancer can benefit from physical activity. Presently, there is an absence of research outside of quantitative investigations on the benefits of structured programs. To enable effective physical activity advice and services, it is important to understand factors that may facilitate or prevent engagement. We therefore explored with women with metastatic breast cancer: (i) personal and behavioural factors that influenced physical activity, and (ii) the role of healthcare services in influencing engagement in being physically active.

Methods: Recruitment took place at a metropolitan cancer centre from November 2019 to January 2020. Women living with metastatic breast cancer were asked to participate in semi-structured interviews about physical activity, covering health-specific factors, goals, barriers, enablers, and interests. Interviews were recorded, transcribed and thematically analysed.

Results: Twenty-three women completed the interview, with a median age of 60 years (IQR: 20) and median time since metastatic diagnosis of 3.3 years (IQR: 3.0). Physical activity ranged from regular participation in structured exercise to simple incidental activity. Seven themes organised into three categories were identified. The category 'personal context' incorporated themes on: (1) both cancer and non-cancer related health factors; (2) time, work and family factors; and (3) exercise history and preferences. The category 'strategies for physical activity' incorporated themes on: (4) self-efficacy, and (5) routine and incidental activity. The category 'role of health and physical activity services' incorporated themes on: (6) tailored education and services, and (7) specific metastatic cancer services and considerations.

Conclusions: Participants expressed diverse experiences with physical activity, with common notions on how physical activity is beneficial but difficult in which to adhere. Whilst some barriers to engagement in physical activity were unique to having cancer, many were not specific to metastatic breast cancer. For example, some participants emphasised specific considerations resulting from their disease, while others primarily reported on general factors such as being time-poor or having conflicting priorities. A patient-centred approach tailored to this group's health and behavioural context may be effective for women who are currently inactive to engage in physical activity.

Background: Cytokeratins are intracellular proteins known as diagnostic biomarkers or prognostic factors for certain cancers. Cytokeratin 19 (CK-19) expression has been proven to have prognostic value for some cancers, but its relationship with others, such as prostate cancer (PCa), remains unclear. This systematic review article aimed to examine the relationship between CK-19 expression and prostate adenocarcinoma (PAC).

Methods: To include the eligible studies that detected CK-19 expression in PAC, published articles since June 2024 were found using PubMed, Scopus, and Web of Science databases. The "prostate cancer" and "cytokeratin 19" keywords and their Mesh term were used for search databases. Data from the included articles were extracted and tabulated. This study was performed using the PRISMA guidelines, and the JBI checklist was used for the quality assessment. The study protocol was registered in PROSPERO under the "CRD42023472637" code.

Results: Twenty-one studies were included. Eleven studies used reverse transcription polymerase chain reaction (RT-PCR) to investigate CK-19 expression, four used immunohistochemistry (IHC) staining, three used both one-step nucleic acid amplification (OSNA) and hematoxylin and eosin (H&E) methods, and three used the electrochemiluminescence (ECL) technique. CK-19 expression was detected in 301 patients among 619 patients. Additionally, only five out of 80 healthy donors were positive for CK-19 expression.

Conclusion: Available evidence indicates a correlation between CK-19 expression and PAC progression, with higher CK-19 levels associated with advanced stages and worse prognosis. The overall evidence suggests that CK-19 could serve as a diagnostic and prognostic marker in PAC.

Background: Colorectal cancer (CRC) is a common gastrointestinal cancer, and even though oxaliplatin chemotherapy is effective, there is a high likelihood of relapse, indicating the presence of oxaliplatin-resistant CRC. Therefore, it is crucial to comprehend the molecular mechanisms of oxaliplatin resistance and develop effective strategies to counter drug resistance. Numerous studies have demonstrated the close association between microRNAs (miRNAs) and drug resistance in CRC. In this study, we aimed to identify the essential exosomal and cellular miRNA related to oxaliplatin resistance in the CRC cell line HCT-116.

Methods: The miRNA expression profile of CRC cells with resistance to oxaliplatin was analyzed. The effectiveness of diagnostics and biomarker potency of miRNAs were evaluated by receiver operating characteristic (ROC) analysis. Target miRNAs were identified, and the enrichment analysis was assessed based on Gene Ontology (GO), Reactome, and Human Disease Ontology (DO). In vitro experiments, oxaliplatin-resistant HCT-116 cells (HCT116-OXA) were developed, and the exosomes were isolated and characterized from HCT116-OXA and HCT116 cells. The expression of the selected miRNAs was evaluated in HCT116-OXA cells and their exosomes, and they were compared to HCT-116 cells using quantitative real-time PCR.

Results: This study revealed that a combination of miR-4326, miR-3615, miR-7974, miR-130b-3p, and miR-454-3p exhibited the highest area under the curve (AUC), sensitivity, specificity, and superior diagnostic and predictive performance. In vitro experiments, HCT116-OXA cells displayed reduced early and late apoptosis, a bypass of S phase arrest, prolonged doubling time, and higher IC₅₀ compared to parental cells. The expression of miR-454-3p, miR-130b-3p, miR-7974, miR-3615, and miR-4326 was decreased in HCT116-OXA cells as compared to sensitive cells. However, a significantly higher expression of miR-130b-3p and miR-4326 was observed in the isolated exosomes of HCT116-OXA cells as compared to the sensitive cells.

Conclusions: The low expression of miR-454-3p, miR-7974, and miR-3615 in CRC cells or high expression of miR-130b-3p and miR-4326 in isolated exosomes could predict the response to oxaliplatin therapy. This indicates the potential of these specific miRNAs to serve as predictive markers for the response to oxaliplatin therapy.

Background: Inadequate treatment responses, chemotherapy resistance, significant heterogeneity, and lengthy treatment durations create an urgent need for new pancreatic cancer therapies. This study aims to investigate the effectiveness of gemcitabine-loaded nanoparticles enclosed in an organo-metallic framework under ketogenic conditions in inhibiting the growth of MIA-PaCa-2 cells.

Methods: Gemcitabine was encapsulated in Metal-organic frameworks (MOFs) and its morphology and size distribution were examined using transmission electron microscopy (TEM) and Dynamic light scattering (DLS) with further characterization including FTIR analysis. Various drug groups were established to evaluate their influences on cell cytotoxicity, apoptosis rate, cell cycle distribution, levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), and cell migration.

Results: The gemcitabine-MOF was thoroughly analyzed to determine its size, morphology, and chemical composition, confirming its successful preparation. The treatment results showed an increase in the number of apoptotic cells following gemcitabine-MOF treatment, which was found to be associated with cell cycle arrest in the sub-G1 phase. Moreover, these treatments also resulted in reduced cell migration, decreased activity of antioxidant enzymes (SOD, GPx), and increased accumulation of MDA. Additionally, when exposed to ketogenic conditions (where beta-hydroxybutyrate is present in a glucose-limited medium), there was a further increase in cell cycle arrest, accompanied by a more pronounced decrease in SOD and GPx activity, as well as decreased migration.

Conclusion: The use of metal-organic framework to encapsulate gemcitabine yielded notable pro-apoptotic effects in MIA-PaCa-2 cells with which ketogenic conditions had a synergistic effect that can hold promise for improving therapeutic options.

Background: LINC00312 has shown to play a suppressive role in the development and progression of non-small cell lung cancer (NSCLC). However, the expression pattern and diagnostic role of circulating LINC00312 in NSCLC remain to be confused.

Methods: A total of 319 patients diagnosed with NSCLC and 180 healthy volunteers were enrolled from the First Affiliated Hospital of Huzhou University between January, 2022 and December, 2023. The participates were randomly assigned into the training and validation groups with a ratio of 6:4, while the remaining was named as the exosomal group. Reverse transcription-quantitative PCR (RT-qPCR) was employed to investigate the expression pattern of LINC00312 in NSCLC tissues, serum samples and cell lines. Receiver operating characteristic (ROC) curve analysis was carried out for distinguishing NSCLC from healthy volunteers.

Results: Here, we revealed that LINC00312 was lowly expressed in NSCLC and low LINC00312 expression manifested a poor prognosis. Additionally, compared with the healthy volunteer group, a reduction of circulating LINC00312 in patients with NSCLC was observed in both the training and validation groups. Further correlation analysis indicated that circulating LINC00312 expression was tightly associated with lymph node metastasis, cancer thrombus, spread through air space (STAS) status and pathological type. Moreover, circulating LINC00312 showed a good performance to distinguish NSCLC from healthy volunteers with a higher sensitivity and specificity values. Lastly, exosomal LINC00312 level was also decreased in NSCLC compared with in healthy volunteers.

Conclusions: Taken together, these data unveil that circulating LINC00312 was notably downregulated in NSCLC, offering a novel non-invasive marker for diagnosis of NSCLC.

Background/aims: Gastric cancer (GC) is a significant global health issue with high incidence rates and poor prognoses, ranking among the top prevalent cancers worldwide. Due to undesirable side effects and drug resistance, there is a pressing need for the development of novel therapeutic strategies. Understanding the interconnectedness of the JAK2/STAT3/mTOR/PI3K pathway in tumorigenesis and the role of Astaxanthin (ASX), a red ketocarotenoid member of xanthophylls and potent antioxidant and anti-tumor activity, can be effective for cancer treatments. This study aimed to investigate the effect of ASX-loaded nanoparticles on the survival of MKN-45 GC cells and the expression of JAK2/STAT3/mTOR/PI3K, offering insights into potential targeted therapies for GC.

Methods: The growth status and survival rate of MKN-45 GC cell lines were determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide(MTT) assay, and the optimal IC50 concentration of ASX, PLGA, and ASX + PLGA was estimated. Also, the clonogenic assay was performed to determine the reproductive power and colony formation of under-treatment cells. Apoptosis and necroptosis of cells were evaluated using acridine orange (AO) staining. The western blot assessed the protein's level of expression and intensity (JAK2/STAT3/mTOR/PI3K). SPSS version 16 software was used for statistical analysis, P-value was considered lower than 0.05.

Results: Based on the results, increasing concentrations of ASX and ASX + PLGA led to a decrease in the viability of MKN-45 cells compared to the control group (P < 0.001). This value was lower for cells treated with ASX + PLGA (P = 0.003). The IC50 values for each of the studied groups (ASX, ASX + PLGA, and PLGA) were 81.45 µg/ml, 51.45 µg/ml, and 3.383 mg/ml, respectively. The levels of expression and intensity of JAK2, STAT3, and mTOR proteins in the Western blotting analysis under ASX + PLGA treatment increased compared to the control group. Conversely, the levels of expression and intensity of P-JAK2, P-STAT3, and P-mTOR proteins in the ASX + PLGA treatment group decreased by 41%, 34%, 37%, and 43%, respectively, compared to the control group. Protein expression levels and intensities of JAK2, STAT3, and mTOR significantly increased when treated with PLGA, ASX, and ASX + PLGA compared to the control group (P < 0.001).

Conclusions: The encapsulation of ASX in PLGA nanoparticles enhances drug stability, enables targeted delivery, and allows for sustained release. This study highlights the therapeutic potential of ASX-loaded nanoparticles in targeting JAK2/STAT3/mTOR/PI3K pathways in GC treatment. Further research is needed to understand the mechanisms and clinical applications of this novel immunotherapy strategy.

Background: This study aims to quantify intratumoral heterogeneity (ITH) using preoperative CT image and evaluate its ability to predict pathological high-grade patterns, specifically micropapillary and/or solid components (MP/S), in patients diagnosed with clinical stage I solid lung adenocarcinoma (LADC).

Methods: In this retrospective study, we enrolled 457 patients who were postoperatively diagnosed with clinical stage I solid LADC from two medical centers, assigning them to either a training set (n = 304) or a test set (n = 153). Sub-regions within the tumor were identified using the K-means method. Both intratumoral ecological diversity features (hereafter referred to as ITH) and conventional radiomics (hereafter referred to as C-radiomics) were extracted to generate ITH scores and C-radiomics scores. Next, univariate and multivariate logistic regression analyses were employed to identify clinical-radiological (Clin-Rad) features associated with the MP/S (+) group for constructing the Clin-Rad classification. Subsequently, a hybrid model which presented as a nomogram was developed, integrating the Clin-Rad classification and ITH score. The performance of models was assessed using the receiver operating characteristic (ROC) curves, and the area under the curve (AUC), accuracy, sensitivity, and specificity were determined.

Results: The ITH score outperformed both C-radiomics scores and Clin-Rad classification, as evidenced by higher AUC values in the training set (0.820 versus 0.810 and 0.700, p = 0.049 and p = 0.031, respectively) and in the test set (0.805 versus 0.771 and 0.732, p = 0.041 and p = 0.025, respectively). Finally, the hybrid model consistently demonstrated robust predictive capabilities in identifying presence of MP/S components, achieving AUC of 0.830 in the training set and 0.849 in the test set (all p < 0.05).

Conclusion: The ITH derived from sub-region within the tumor has been shown to be a reliable predictor for MP/S (+) in clinical stage I solid LADC.

Background: The COVID-19 pandemic involved business closures (e.g., gyms), social distancing policies, and prolonged stressful situations that may have impacted engagement in health behaviors. Our study assessed changes in cancer-related health behaviors during the pandemic, specifically physical activity, fruit/vegetable intake, smoking/tobacco use, and alcohol consumption.

Methods: Eight cancer centers administered mailed/web-based/telephone surveys between June 2020 and March 2021. Surveys assessed demographics, perceptions on social distancing, and self-reported changes of behaviors (less/same/more) associated with cancer prevention or risk, e.g., physical activity, fruit/vegetable intake, tobacco/smoking use, and alcohol consumption. Descriptive analyses and logistic regression models assessed association of variables with behavior change.

Results: Most of the 21,911 respondents reported adhering to at least 4(of 5) social distancing measures (72%) and indicated social distancing was very/somewhat important to prevent the spread of COVID-19 (91%). 35% of respondents reported less physical activity, 11% reported less fruit/vegetable intake, 27% reported more smoking/tobacco use (among those who used tobacco/smoking products in past 30 days), and 23% reported more alcohol consumption (among those who reported at least 1 drink in past 30 days) than before the pandemic. Urban residence, younger age, female gender, and worse general health were associated with less physical activity, less fruit/vegetable intake, more smoking/tobacco use, and more alcohol intake. Higher educational attainment was associated with less physical activity and fruit/vegetable intake and more alcohol consumption. Reporting social distancing as important and adhering to more COVID-19 safety practices were associated with less physical activity and more alcohol consumption.

Conclusion: Our findings suggest that certain demographics and those who adhered to social distancing measures were more likely to self-report unfavorable changes in health behaviors during the pandemic. Future studies should examine if the behaviors returned to baseline following relief from pandemic restrictions, and if these behavior changes are associated with increased cancer incidence and mortality.