BMC Cancer最新文献

Objectives: To construct a prediction model based on deep learning (DL) and radiomics features of diffusion weighted imaging (DWI), and clinical variables for evaluating TP53 mutations in endometrial cancer (EC).

Methods: DWI and clinical data from 155 EC patients were included in this study, consisting of 80 in the training set, 35 in the test set, and 40 in the external validation set. Radiomics features, convolutional neural network-based DL features, and clinical variables were analyzed. Feature selection was performed using Mann-Whitney U test, LASSO regression, and SelectKBest. Prediction models were established by gaussian process (GP) and decision tree (DT) algorithms and evaluated by the area under the receiver operating characteristic curve (AUC), net reclassification index (NRI), calibration curves, and decision curve analysis (DCA).

Results: Compared to the DL (AUC_training = 0.830, AUC_test = 0.779, and AUC_validation = 0.711), radiomics (AUC_training = 0.810, AUC_test = 0.710, and AUC_validation = 0.839), and clinical (AUC_training = 0.780, AUC_test = 0.685, and AUC_validation = 0.695) models, the combined model based on the GP algorithm, which consisted of four DL features, five radiomics features, and two clinical variables, not only demonstrated the highest diagnostic efficacy (AUC_training = 0.949, AUC_test = 0.877, and AUC_validation = 0.914) but also led to an improvement in risk reclassification of the TP53 mutation (NIR_training = 66.38%, 56.98%, and 83.48%, NIR_test = 50.72%, 80.43%, and 89.49%, and NIR_validation = 64.58%, 87.50%, and 120.83%, respectively). In addition, the combined model exhibited good agreement and clinical utility in calibration curves and DCA analyses, respectively.

Conclusions: A prediction model based on the GP algorithm and consisting of DL and radiomics features of DWI as well as clinical variables can effectively assess TP53 mutation in EC.

Background: Triple-negative breast cancer (TNBC) is among the most aggressive forms of breast cancer, characterized by a dismal prognosis. In the absence of drug-targetable receptors, chemotherapy remains the sole systemic treatment alternative. Recent advancements in immunotherapy, particularly immune checkpoint inhibitors (ICIs) that target programmed death 1/programmed death ligand 1 (PD-1/PD-L1) and cytotoxic T lymphocyte associated antigen 4 (CTLA-4), have provided renewed optimism for the treatment of patients with TNBC. Prior research has indicated that the expression level of the cell polarity protein discs large homolog 5 (DLG5) correlates with the malignant progression and prognosis of breast cancer; nevertheless, its influence on PD-L1 expression and its function in immunotherapy for TNBC require further investigation.

Methods: The hypoxia cell model was established by simulating the cell hypoxic microenvironment in the human SUM159 and MDA-MB-231 cell lines using cobalt II chloride (CoCl₂). A combination of PD-L1 inhibitors and DLG5 RNA interference techniques was used, along with various methods including cell counting kit-8 (CCK-8), colony formation, wound healing, transwell migration, reverse transcription-quantitative real-time PCR (RT-qPCR), immunofluorescence, immunohistochemical staining (IHC), expression analysis from datasets and western blotting. These methods were employed to evaluate changes in cell proliferation, migration, and the expression levels of PD-L1 and DLG5. Additionally, the correlation between the expression of PD-L1 and DLG5 in clinical samples was analyzed.

Results: (1) In vitro experiments, a cellular hypoxia model was effectively established utilizing 150 µM CoCl₂. Under these conditions, cell clone formation, invasiveness, and migration rate were all significantly inhibited. (2) The expression levels of DLG5 and PD-L1 were significantly increased in both MDA-MB-231 and SUM159 cells following treatment with 150 µM CoCl₂. (3) Silencing DLG5 resulted in a considerable upregulation of PD-L1 expression in MDA-MB-231 and SUM159 cells under normoxic circumstances, but it was markedly downregulated under hypoxic settings. Inhibition of PD-L1 expression resulted in a considerable increase in DLG5 expression under normoxic conditions, but it decreased under hypoxic conditions. Correlation research demonstrated an inverse association between the expression of DLG5 and PD-L1 in TNBC tissues.

Conclusion: This study provides new theoretical evidence and potential therapeutic targets for the immunotherapy strategies of TNBC, holding significant clinical application value.

Objective: Sarcopenia, a condition characterized by the gradual decline of muscle mass, strength, and function, is a key indicator of malnutrition in cancer patients and has been linked to poor prognoses in oncology. Sarcopenia is commonly assessed by measuring the skeletal muscle index (SMI) of the third lumbar spine (L3) using computed tomography (CT). This meta-analysis aimed to explore the relationship between low SMI and clinicopathological features, as well as prognosis, in individuals with endometrial cancer (EC).

Methods: Data from various databases including PubMed, Embase, Cochrane, Medline, and Web of Science were searched up until October 20th, 2024. Studies that investigated the association of low SMI and EC survival or clinicopathological characteristics were included. Pooled effect sizes were reported as hazards ratio (HR), odds ratios (ORs) or weighted mean difference (WMD). The quality and risk of bias in the studies were evaluated using the Newcastle-Ottawa Scale (NOS) and the Quality In Prognosis Studies (QUIPS), and the study was registered on PROSPERO (CRD42024509949) before commencing the search.

Results: A total of 218 studies were identified across all five databases, with 11 studies meeting the criteria for qualitative and quantitative analysis, involving 1588 patients. The findings of our meta-analysis demonstrated a significant link between low SMI and progression-free survival [P = 0.002; HR: 1.62, 95% CI: 1.20-2.17]. Low SMI was also associated with a BMI < 25 (P < 0.00001; OR: 4.55, 95% CI: 3.01-6.87), FIGO stage (P = 0.04; OR: 1.33, 95% CI: 1.01-1.75), pathology grades (P = 0.001; OR: 1.77, 95% CI: 1.26-2.49), and the endometrioid pathological type (P = 0.01; OR: 0.68, 95% CI: 0.51-0.92). However, no significant correlation was found between low SMI and 5-year overall survival, serous pathological type, recurrence, length of hospital stay, intraoperative complications, and postoperative complications. All the included studies scored ≥ 7 on the NOS, indicating relatively high-quality evidence.

Conclusions: The meta-analysis highlighted the association between low SMI and unfavorable clinical features and outcomes in EC patients, emphasizing the importance of early diagnosis and appropriate management of sarcopenia assessed by low SMI to enhance prognoses in EC patients.

Background: Arterial hypertension is one of the most frequent comorbidities in patients with cancer. Studies have indicated that drugs used to control hypertension may alter cancer patient survival; however, epidemiological findings for their impact on cancer survival remain inconsistent. The aim of this study was to examine the effect of the consumption of antihypertensive (AH) medication on the risk of death in cancer patients.

Methods: The association between 1-year postdiagnostic AH medication intake and the risk of death was examined in a population-based cohort of cancer patients including colorectal (N = 1104), lung (N = 344), melanoma (N = 334), corpus uteri (N = 832) and kidney cancer (N = 714), diagnosed between 2013 and 2015, and identified from the Lithuanian Cancer Registry. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HRs), and corresponding 95% confidence intervals (95% CI) to assess associations between AH medications and cancer-specific and overall mortality.

Results: We found a statistically significant decrease in mortality among colorectal cancer patients who were users of angiotensin receptor blockers (ARBs) (HR: 0.68, 95% CI: 0.47-0.98) or angiotensin converting enzyme inhibitors (ACEIs) (HR: 0.69, 95% CI: 0.52-0.91). A higher usage of ARBs and ACEIs was related to further improved colorectal cancer survival (HR 0.62, 95% CI: 0.39-1.00 and HR 0.60, 95% CI: 0.42-0.86, respectively). The subgroup analyses also demonstrated significantly better cancer specific survival in ARB users and ACEI users versus non-users in colorectal cancer patients with adenocarcinoma, surgery treatment, chemotherapy treatment and ARB or ACEI use before diagnosis. The results suggest a lower mortality among colorectal cancer patients with a higher usage of diuretics. Increased cancer-specific mortality was observed among corpus uteri cancer patients using ARBs and among melanoma patients using beta blockers (BBs); however, there was no evidence of consistent statistically significant associations in subgroup analyses.

Conclusion: This study supports a link between ARB and ACEI use and increased survival among colorectal cancer patients. Further research is needed to provide a detailed evaluation of the effects of AH medications on cancer survival.

Background: nowadays, the photoacoustic imaging is in the mainstream of cancer theranostics. In this study the nanoparticles with previously proven photoacoustic imaging properties, i.e. glucose-ethylenediamine carbon dots (GE-NPs), were tested for photoacoustic cancer therapy.

Methods: nanoparticle biocompatibility was analyzed in cell toxicity and neurotoxicity experiments ex vivo. Biochemical parameters were analyzed in animal experiments in vivo after intramuscular implantation of Lewis Lung carcinoma cells into the C57/Black mouse line.

Results: GE-NPs at concentrations of 0.1-1.0 mg/ml did not change the extracellular level, exocytotic and transporter-mediated release, as well as the initial rate of uptake and accumulation of L-[¹⁴C]glutamate in isolated rat brain nerve terminals. GE-NP-treated mice had evidence of the probable protection of the liver and attenuating the systemic consequences of tumor growth, as evidenced by normalization of serum aspartate aminotransferase (ASAT), and lactate dehydrogenase (LDH) levels, compared to vehicle-dosed tumor-bearing animals. According to hematological analysis, treatment with GE-NPs caused an increase in red blood cells and hematocrit up to the healthy control levels. When a combination of GE-NPs (1 mg/ml) is injected into a mouse tumor and the tumor is irradiated by a laser beam, it leads to an increase in mice survival by more than 30% compared to GE-NPs-treated non-irradiated mice, and a decrease in the growth rate of the cancerous tumor. The observed therapeutic effect can be related to the photoacoustically-induced destruction of cancer cells significantly enhanced by the presence of the incorporated GE-NPs, because the laser-induced localized heating of mice skin has not exceeded 2 °C.

Conclusions: the efficiency of photoacoustic therapy of Lewis Lung carcinoma in mice using biocompatible carbon dots was demonstrated. Biocompatible GE-NPs own multimodal potential in cancer theranostics, including both photoacoustic imaging and therapy, by applying different irradiation conditions.

Background: The diagnosis of rare uterine leiomyosarcoma (uLMS) remains a challenge given the high incidence rates of benign uterine tumors such as leiomyoma (LM). In the last decade, several clinical scores and blood serum markers have been proposed. The aim of this study is to validate and update the pLMS clinical scoring system, evaluating the accuracy of the scoring system by Zhang et al. and examining the discriminatory ability of blood markers such as serum lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR).

Methods: In a case-control study, 90 new uLMS from the DKSM consultation registry and 659 prospectively recruited LM cases from the Saarland University Hospital were used for validation. Welch's t-test and Hedges' g were used to evaluate blood markers and optimal thresholds and diagnostic odds ratios were calculated. Scoring systems were compared using receiver operating characteristics and proposed diagnostic cut-offs were reviewed. Missing values were imputed by random forest imputation to create the updated scoring system 'pLMS2' using penalized logistic regression based on the pooled data sets of 384 uLMS and 1485 LM.

Results: pLMS achieved an AUC of 0.97 on the validation data, but sensitivity and specificity varied at the proposed thresholds due to a shift in the score distributions. 43 uLMS and 578 LM were included in the comparison of pLMS with Zhang's scoring system, with pLMS being superior (AUC 0.960 vs 0.845). LDH, NLR, and PLR achieved a diagnostic odds ratios of 18.03, 8.64 and 4.81, respectively. pLMS2 is based on subscores for menopausal status interacting with age, tumor diameter, intermenstrual bleeding, hypermenorrhea, dysmenorrhea, postmenstrual bleeding, rapid tumor growth, and suspicious sonography.

Conclusions: Validation of the pLMS shows stable discriminatory ability as expressed by AUC, although caution should be taken with cut-off values, as sensitivity and specificity may vary. Data collection of the updated clinical score pLMS2 remains simple and convenient, with no additional cost. The proposed thresholds of 1.5 and 5.5 can be used as a guide to avoid unnecessary or inappropriate surgery and to make the use of further diagnostic measures cost-effective. LDH, NLR and PLR provide further evidence to differentiate uLMS from LM in conjunction with clinical data.

Adjuvant endocrine therapy (AET) is essential for improving survival and reducing mortality and recurrence rates in breast cancer (BrCa) patients. However, the adherence to AET among BrCa patients is poor, and there is no scale to measure adherence to AET or the reasons for non-adherence among BrCa patients in mainland China. The aim of this study was to assess the psychometric properties of the simple Chinese version of the Medication Adherence Reasons (MAR) scale in BrCa patients undergoing AET. This study utilized a cross-sectional research design with two phases: (1) translation and cross-cultural adaptation of the original English version of the MAR scale into simple Chinese and (2) validation of the simple Chinese version of the MAR scale (s-ChMAR scale) in BrCa patients. Instrument assessments included content validity, face validity, item analysis, construct validity, criterion-related validity and reliability testing. This study recruited participants using convenience sampling to investigate adherence to AET among BrCa patients. Inclusion criteria were: (a) female, (b) aged 18 years or older, (c) diagnosed with Stage I to III BrCa, (d) completed primary treatment for hormone receptor-positive BrCa and had been on AET for more than six months but less than five years, (e) proficient in Mandarin, and (f) provided informed consent. Exclusion criteria included psychiatric illness, cognitive impairment, or a diagnosis of another cancer type. The sample size for exploratory factor analysis (EFA) was determined based on a ratio of five to ten participants per scale item to ensure sufficient statistical power. Data were collected from a sample of 325 participants who received AET for over six months. All the items had a content validity index (CVI) of more than 0.80. Regarding construct validity, the s-ChMAR scale fit a four-dimensional model, the same as the original MAR scale tested in asthma patients. The s-ChMAR scale had good internal reliability (Cronbach's α = 0.896) and good stability (ICC = 0.837). In terms of quantifying non-adherence, the s-ChMAR scale identified a non-adherent participant rate of over 50%. The study findings support the reliability and validity of the s-ChMAR scale in measuring the non-adherence of Chinese BrCa patients to AET.

Background: Our goal is to develop a nomogram model to predict overall survival (OS) for elderly esophageal squamous cell carcinoma (ESCC) patients receiving definitive radiotherapy (RT) or concurrent chemoradiotherapy (CRT), aiding clinicians in personalized treatment planning with a risk stratification system.

Methods: A retrospective study was conducted on 718 elderly ESCC patients treated with RT or CRT at 10 medical centers (3JECROG) from January 2004 to November 2016. We identified independent prognostic factors using univariate and multifactorial Cox regression to construct a nomogram model. Its effectiveness was evaluated using concordance statistics (C-index), area under the curve (AUC), net reclassification index (NRI), and integrated discrimination improvement (IDI), and compared against the AJCC staging. Additionally, decision curve analysis (DCA) assessed the model's clinical benefit. Patients were stratified into low, intermediate, and high-risk groups using the nomogram, and their prognoses in various disease stages were analyzed.

Results: Significant prognostic factors identified included diabetes, tumor volume (GTVp), tumor length, location, and clinical stages (T, N, M), and RT response. Multivariate analysis confirmed these as independent factors for OS. The nomogram outperformed AJCC staging in prediction accuracy and discrimination, evidenced by a higher C-index, better AUC, and significant NRI and IDI values. Patients categorized by the nomogram demonstrated distinct 5-year OS rates, with a higher C-index than AJCC staging (0.597 vs. 0.562) .

Conclusions: The study identified key prognostic factors for elderly ESCC patients receiving RT or CRT. The nomogram model, based on these factors, showed enhanced prediction performance, discrimination, and clinical utility compared to AJCC staging. This risk stratification provided more accurate survival predictions and aided in personalized risk management.