BMC Cancer最新文献

Background: Multiple first-line treatment options have been developed for advanced non-small cell lung cancer (NSCLC) in each subgroup determined by predictive biomarkers, specifically driver oncogene and programmed cell death ligand-1 (PD-L1) status. However, the methodology for optimal treatment selection in individual patients is not established. This study aimed to develop artificial intelligence (AI)-based personalized survival prediction model according to treatment selection.

Methods: The prediction model was built based on random survival forest (RSF) algorithm using patient characteristics, anticancer treatment histories, and radiomics features of the primary tumor. The predictive accuracy was validated with external test data and compared with that of cox proportional hazard (CPH) model.

Results: A total of 459 patients (training, n = 299; test, n = 160) with advanced NSCLC were enrolled. The algorithm identified following features as significant factors associated with survival: age, sex, performance status, Brinkman index, comorbidity of chronic obstructive pulmonary disease, histology, stage, driver oncogene status, tumor PD-L1 expression, administered anticancer agent, six markers of blood test (sodium, lactate dehydrogenase, etc.), and three radiomics features associated with tumor texture, volume, and shape. The C-index of RSF model for test data was 0.841, which was higher than that of CPH model (0.775, P < 0.001). Furthermore, the RSF model enabled to identify poor survivor treated with pembrolizumab because of tumor PD-L1 high expression and those treated with driver oncogene targeted therapy according to driver oncogene status.

Conclusions: The proposed AI-based algorithm accurately predicted the survival of each patient with advanced NSCLC. The AI-based methodology will contribute to personalized medicine.

Trial registration: The trial design was retrospectively registered study performed in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Nagoya University Graduate School of Medicine (approval: 2020 - 0287).

Background: There is no relevant research on the symptoms and emotions of patients with advanced thyroid cancer in mainland China.

Aim: To investigate the symptoms and negative emotions of patients with advanced thyroid cancer and to analyze the correlation between the two preliminarily.

Methods: Using a convenience sampling method, 180 patients who visited a multidisciplinary outpatient service for advanced thyroid cancer at West China Hospital of Sichuan University from January 2023 to December 2023 were selected as the research subjects. A cross-sectional survey was conducted using the M.D. Anderson Symptom Inventory-Thyroid Cancer module (MDASI-THY) and Hospital Anxiety and Depression Scale (HADS). The correlation between symptom severity and negative emotions was determined by Spearman correlation analysis.

Results: Disturbed sleep was the symptom with the highest incidence (74.4%) and the greatest severity (3.0 points), while mood distress was the symptom with the highest incidence (63.3%) and the greatest severity (2.0 points). 71 patients (39.4%) had anxiety, and 62 patients (34.4%) had depression. All symptoms and symptom interference were positively correlated with anxiety and depression (P < 0.05).

Conclusion: Patients with advanced thyroid cancer have multiple symptoms that seriously affect their daily lives and emotions. Medical staff should conduct targeted observation and preventive treatment to reduce the burden of symptoms and improve the negative emotions of patients.

Objective: Many investigation have sought to identify therapeutic targets and treatment strategies for skin cutaneous melanoma (SKCM). Numb, an endocytic adaptor protein, is known to act as a tumor suppressor in various human cancers. However, the roles of Numb and its homolog NumbL in immune microenvironment, and their effect on melanoma remain largely unexplored.

Methods: We analyzed the expression levels of Numb and NumbL, as well as immune signatures of SKCM patients by UCSCXenaShiny v1 database. We also constructed animal model using Numb and NumbL conditional knockout (cKO) mice. Distribution analysis of immune cells in tumors was performed by flow cytometry and pathology staining.

Results: Numb and NumbL were found to be consistently expressed at low levels in SKCM patients. In addition, alterations in tumor immune microenvironment were identified. The CD8⁺ T, CD19⁺ B, and NK1.1⁺ CD49⁺ cells were decreased in tumors of Numb and NumbL cKO mice, confirming previous bioinformatics analysis of immune signatures. Additionally, we observed CD68⁺ macrophages to be increased as judged by tumor pathology staining.

Conclusion: Numb and NumbL were found to inhibit melanoma cell growth by modulating immune cell activity. These results suggested that Numb and NumbL may be potential therapeutic targets for SKCM patient immunotherapy.

Background: Gastric cancer poses a significant global health challenge. We aim to use period analysis to assess the changes in gastric cancer treatment at our center over the past 15 years. This study reflects the current state of gastric cancer treatment at our center and provides valuable data to support clinical advancements.

Method: We used period analysis to evaluate the survival status of 3915 patients with gastric cancer at Nanfang Hospital, Southern Medical University, over a 15-year period spaning from 2008 to 2022. The 5-year relative survival rates were analyzed.

Result: Our findings indicate that the 5-year relative survival rate at our center from 2018 to 2022 is 71.4%. From 2018 to 2022, the 5-year relative survival rates for patients aged < 40, 40-54, 55-69, and ≥ 70 reached 67.5%, 73.5%, 72.0%, and 67.1%, respectively. For stage IV patients, the 5-year relative survival rate reached 29% in 2018-2022. For stage I-III patients, the 5-year relative survival rate reached 89.7% in 2018-2022. The five-year relative survival rate for patients who underwent laparoscopic surgery at our center rose from 50.3% in 2008-2012 to 71.4% in 2018-2022. Overall, there has been a notable increase in the 5-year relative survival rates, regardless of age, gender, region, or tumor stage.

Conclusion: Period analysis over the past 15 years shows significant improvement in the 5-year survival rate for gastric cancer at our center. This progress is due to standardized surgical techniques, perioperative management, and immunotherapy, providing robust data for evaluating the efficacy of recent treatments.

Purpose: To identify more reliable imaging and serological indicators for predicting Ki-67 expression and malignant potential in gastrointestinal stromal tumors, as well as to develop a preoperative prediction model with clinical utility.

Patients and methods: This study retrospectively analyzed patients with gastrointestinal stromal tumors (GIST) diagnosed at the First Affiliated Hospital of Jinzhou Medical University between May 2018 and May 2024. Univariate logistic analyses, two-way stepwise regression, P-value stepwise regression, and LASSO regression were employed to screen for Ki-67 high expression and high malignant potential risk factors associated with GIST. Models were established using various regression methods; Nomograms, calibration curves, and clinical decision curves were generated for the two best prediction models.

Results: Two-way stepwise regression analysis revealed that diameter (P=0.037; OR=1.22; 95% CI: 1.01 - 1.46), growth pattern (extraluminal type: P=0.028; OR=3.54; 95% CI: 1.14 - 10.94), enhancement model (P=0.099; OR=0.39; 95% CI: 0.12 - 1.20), EVFDM (P=0.069; OR=0.43; 95% CI: 0.17 - 1.07), PLR (P=0.099; OR=3.06; 95% CI: 0.81 - 11.59), and OPNI (P=0.058; OR=2.38; 95% CI: 0.97 - 5.84) are identified as independent risk factors for Ki-67 expression. Utilizing the two-way stepwise regression model to predict Ki-67 expression, the area under the curve (AUC) for the training group was 0.865 (95% CI: 0.807-0.922), while for the validation group it was 0.784 (95% CI: 0.631-0.937). The Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC) for the training group were 153.360 and 174.619, respectively. Two-way stepwise regression analysis revealed that volume (P < .001, OR = 1.06; 95% CI: 1.03 - 1.09), contour (P = 0.066; OR = 0.17; 95% CI: 0.05 - 0.62), ulcer (P = 0.094; OR = 0.16; 95% CI: 0.03 - 0.98), IBSC (P = 0.008; OR = 5.27; 95% CI: 1.57 - 17.69), and OPNI (P = 0.045; OR = 0.22; 95% CI: 0.05 - 0.96) are independent risk factors for malignant potential. Utilizing the two-way stepwise regression model to predict malignant potential, the AUC for the training group was 0.950 (95% CI: 0.920 - 0.980), while for the validation group it was 0.936 (95% CI: 0.867 - 1.000). The AIC and BIC values for the training group were 96.330 and 114.552, respectively.

Conclusion: Diameter, growth pattern, enhancement pattern, EVFDM, PLR, and OPNI are independent risk factors for GIST with high Ki-67 expression. Additionally, volume, contour, ulceration, IBSC, and OPNI serve as independent risk factors for GIST with high malignant potential. The preoperative models developed using CT images can predict the malignant potential and Ki-67 expression status of GIST to a certain extent. When combined with serological indicators, these models' predictive performance can be further enhanced.

Background: Thyroid cancer is ranked as the most common malignancy within the endocrine system and the seventh most prevalent cancer in women globally. Thyroid malignancies require evaluating biomarkers capable of distinguishing between them for accurate diagnosis. We examined both mRNA and protein levels of TSPAN1 in plasma and tissue samples from individuals with thyroid nodules to aid this endeavour.

Methods: In this case-control study, TSPAN1 was assessed at both protein and mRNA levels in 90 subjects, including papillary thyroid cancer (PTC; N = 60), benign (N = 30), and healthy subjects (N = 26) using enzyme-linked immunosorbent assay (ELISA) and SYBR-Green Real-Time PCR, respectively.

Results: TSPAN1 plasma levels were decreased in PTC and benign compared to healthy subjects (P = 0.002). TSPAN1 mRNA levels were also decremented in the tumoral compared to the paired normal tissues (P = 0.012); this drop was also observed in PTC patients compared to benign patients (P = 0.001). Further, TSPAN1 had an appropriate diagnostic value for detecting PTC patients from healthy plasma samples with a sensitivity of 76.7% and specificity of 65.4% at the cutoff value < 2.7 (ng/ml).

Conclusion: TSPAN1 levels are significantly reduced in patients with benign and PTC, demonstrating its potential value as a diagnostic biomarker. Additionally, the significant reduction in TSPAN1 mRNA expression within PTC tumor tissues may suggest its involvement in tumor progression and development. Further studies, including larger-scale validation studies and mechanistic investigations, are imperative to clarify the molecular mechanisms behind TSPAN1 and, ultimately, its clinical utility for treating thyroid disorders.

Background: Cancer cells alter their metabolic phenotypes with nutritional change. Single agent approaches targeting mitochondrial metabolism in cancer have failed due to either dose limiting off target toxicities, or lack of significant efficacy in vivo. To mitigate these clinical challenges, we investigated the potential utility of repurposing FDA approved mitochondrial targeting anthelmintic agents, niclosamide, IMD-0354 and pyrvinium pamoate, to be combined with GLUT1 inhibitor BAY-876 to enhance the inhibitory capacity of the major metabolic phenotypes exhibited by tumors.

Methods: To test this, we used breast cancer cell lines MDA-MB-231 and 4T1 which exhibit differing basal metabolic rates of glycolysis and mitochondrial respiration, respectively. Metabolic characterization was carried out using Seahorse XFe96 Bioanalyzer and statistical analysis was carried out via ANOVA.

Results: Here, we found that specific responses to mitochondrial and glycolysis targeting agents elicit responses that correlate with tested cell lines basal metabolic rates and fuel preference, highlighting the potential to cater metabolism targeting treatment regimens based on specific tumor nutrient handling. Inhibition of GLUT1 with BAY-876 potently inhibited glycolysis in both MDA-MB-231 and 4T1 cells, and niclosamide and pyrvinium pamoate perturbed mitochondrial respiration that resulted in potent compensatory glycolysis in the cell lines tested.

Conclusion: In this regard, combination of BAY-876 with both mitochondrial targeting agents resulted in inhibition of compensatory glycolysis and subsequent metabolic crisis. These studies highlight targeting tumor metabolism as a combination treatment regimen that can be tailored by basal and compensatory metabolic phenotypes.

Background and objectives: Currently, research on the role of B cells in esophageal cancer (EC) is limited, and existing studies on their impact are controversial. Therefore, this study was conducted to elucidate the complex causal relationship between B cells and EC, expand the understanding of esophageal cancer immunology.

Methods: Bidirectional two-sample Mendelian randomization (MR) was performed to assess the causal relationships between 190 B cell phenotypes and EC. To complement the MR analysis, Bayesian Weighted Mendelian Randomization (BWMR) was employed, and sensitivity analyses were conducted to evaluate the robustness of the findings. Positive results were further validated in independent cohorts of esophageal cancer studies. In addition, RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) were utilized for validation, incorporating B cell-related gene expression analysis and functional enrichment analysis to support the MR findings.

Results: In the primary analysis, significant causal relationships were observed between 5 B cell types and the risk of EC; the onset of EC was causally linked to 3 B cell phenotypes. Validation in other cohorts revealed that 4 outcomes aligned with the primary analysis, included were CD19 on IgD + CD38-, CD20 on IgD- CD27-, CD20 on IgD- CD38br, and CD38 on PB/PC. Further validation using RNA-seq data showed that CD38 mRNA was significantly overexpressed in EC tissues, whereas CD19 and MS4A1 mRNA levels did not differ significantly between tumor and normal tissues. Functional enrichment analysis revealed that CD19, MS4A1, and CD38 are involved in multiple tumor-related immune pathways, suggesting their pivotal role in regulating the tumor immune microenvironment.

Conclusions: Our study suggests a potential connection between B cell phenotypes and EC through bidirectional two-sample MR combined with BWMR analysis, providing a preliminary basis for future research.

Objective: To investigate the specificity of Target of Myb1-Like1 (Tom1L1) expression in colorectal adenocarcinoma tissues and analyze the predictive value of Tom1L1 in the efficacy of neoadjuvant chemotherapy for patients with rectal adenocarcinoma.

Methods: The cancerous tissues and paracancerous normal tissues of 102 patients diagnosed with colorectal adenocarcinoma without treatment were selected; quantitative polymerase chain reaction (qPCR), Western blot and immunohistochemistry (IHC) were adopted to validate the expression level of Tom1L1 in the two groups. Furthermore, 34 patients with locally progressive mid-low rectal adenocarcinoma, who were treated with neoadjuvant Xelox chemotherapy prior to the operation, IHC was adopted to detect the expression of Tom1L1 protein in patients before and after neoadjuvant chemotherapy and to analyze the relationship between the expression level of Tom1L1 and the sensitivity of neoadjuvant therapy.

Results: The results of qPCR, Western blot and IHC showed that the expression of Tom1L1 in colorectal adenocarcinoma tissues was significantly higher than that in paracancerous normal tissues, with a statistically significant difference (P < 0.01); Neoadjuvant chemotherapy was significantly more effective in patients with low expression of Tom1L1 protein than in those with high expression of Tom1L1 protein, with a statistically significant difference (P < 0.05).

Conclusions: Tom1L1 is highly expressed in colorectal adenocarcinoma tissues; neoadjuvant Xelox chemotherapy can have an impact on Tom1L1 expression in progressive rectal cancer; patients with locally progressive mid-low rectal adenocarcinoma who have low Tom1L1 expression are more sensitive to neoadjuvant chemotherapy.

Background: Colorectal cancer (CRC) is a leading cause of cancer-related mortality, highlighting the necessity for multifaceted treatment strategies, including preoperative treatment (PT), which can enhance surgical outcomes and provide prognostic insights. This study aims to clarify the impact of PT-induced changes in mismatch repair (MMR) and human epidermal growth factor receptor 2 (HER2) expression, potentially informing tailored treatment strategies and improving clinical outcomes for CRC patients.

Methods: This retrospective study analyzed 120 paired samples from CRC patients who underwent preoperative treatment, comparing pre- and post-treatment specimens. A control group of 60 untreated surgical specimens was also included. Immunohistochemistry assessed MMR proteins (MSH6, MSH2, MLH1, PMS2) and HER2 expression. MSI status was determined in samples with low MMR expression.

Results: Compared to pre-treatment samples, post-treatment samples exhibited lower levels of MSH6, MSH2, and total MMR expression, along with higher levels of HER2 expression. However, when compared to the untreated control group, there were no significant differences in the expression of MSH6, total MMR, and HER2. All samples that exhibited weak MMR expression and those that shifted to deficient mismatch repair (dMMR) status following treatment had stable microsatellite status. No clear clinicopathological characteristics or prognostic factors were found to be associated with changes in MMR and HER2 expression, except for the use of fluorouracil or capecitabine, which was related to changes in total MMR scores. ypTNM stage and TRG scores were identified as independent factors affecting disease progression in our study.

Conclusions: PT is associated with a reduction in MMR expression, notably for the MSH2 protein, while it does not appear to influence HER2 expression.