BMC Cancer最新文献

Objective: This investigation attempted to examine the effectiveness of CT-derived peritumoral and intratumoral radiomics in forecasting microsatellite instability (MSI) status preoperatively among gastric cancer (GC) patients.

Methods: A retrospective analysis was performed on GC patients from February 2019 to December 2023 across three healthcare institutions. 364 patients (including 41 microsatellite instability-high (MSI-H) and 323 microsatellite instability-low/stable (MSI-L/S)) were stratified into a training set (n = 202), an internal validation set (n = 84), and an external validation set (n = 78). Radiomics features were obtained from both the intratumoral region (IR) and the intratumoral plus 3-mm peritumoral region (IPR) on preoperative contrast-enhanced CT images. After standardizing and reducing the dimensionality of these features, six radiomic models were constructed utilizing three machine learning techniques: Support Vector Machine (SVM), Linear Support Vector Classification (LinearSVC), and Logistic Regression (LR). The optimal model was determined by evaluating the Receiver Operating Characteristic (ROC) curve's Area Under the Curve (AUC), and the radiomics score (Radscore) was computed. A clinical model was developed using clinical characteristics and CT semantic features, with the Radscore integrated to create a combined model. Used ROC curves, calibration plots, and Decision Curve Analysis (DCA) to assess the performance of radiomics, clinical, and combined models.

Results: The LinearSVC model using the IPR achieved the highest AUC of 0.802 in the external validation set. The combined model yielded superior AUCs in internal and external validation sets (0.891 and 0.856) in comparison to clinical model [(0.724, P = 0.193) and (0.655, P = 0.072)] and radiomics model [(0.826, P = 0.160) and (0.802, P = 0.068)]. Furthermore, results from calibration and DCA underscored the model's suitability and clinical relevance.

Conclusion: The combined model, which integrates IPR radiomics with clinical characteristics, accurately predicts MSI status and supports the development of personalized treatment strategies.

Background: The role of lipid metabolic reprogramming in the development of various types of cancer has already been established. However, the exact biological function and significance of the elongation of very-long-chain fatty acids (ELOVLs) gene family, which can affect fatty acid metabolism, is still not well understood in lung adenocarcinoma (LUAD). The aim of our study is to explore whether there are genes related to the pathogenesis of LUAD in the ELOVLs family, and even to guide clinical medication and potential prognostic indicators.

Methods: Gene expression profiling interactive analysis (GEPIA), human protein atlas (HPA), cBioPortal, Kaplan-Meier (KM) plotter, single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm and SubMap algorithms were utilized to analyze the role of ELOVLs in the LUAD. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, cell counting kit-8 (CCK8), colony formation, wound healing, transwell migration assays and fatty acid metabolism detection were employed to confirm the significant role of ELOVL6 in vitro experiment.

Results: Our results revealed that mRNA expression levels of ELOVL2, ELOVL4 and ELOVL6 and protein expression levels of ELOVL5 and ELOVL6 were elevated in LUAD tissues compared to normal subjects. The low-expressing ELOVL6 group showed superior overall survival (OS) and disease-specific survival (DSS) versus the high-expressing group. Meanwhile, patients with low-ELOVL6 expression were more sensitive to the 4 representative chemotherapeutic agents. In vitro, we revealed that interfering with ELOVL6 could influence the viability, proliferation, migration capacity and fatty acid metabolism of LUAD cells (A549 and H1299).

Conclusions: Our study indicated that ELOVL6 could be used as an indicator to evaluate the prognosis and therapeutic effect, and even potential therapeutic target for patients with LUAD.

Objective: Neuroendocrine cervical carcinoma (NECC) is a rare but highly aggressive tumor. The clinical management of NECC follows neuroendocrine neoplasms and cervical cancer in general. However, the diagnosis and prognosis of NECC remain dismal. The aim of this study was to identify a specific protein signature for the diagnosis of NECC.

Methods: Protein and gene expression data for NECC and other cervical cancers were retrieved or downloaded from self-collected samples or public resources. Eleven machine-learning algorithms were packaged into 66 combinations, of which we selected the optimal algorithm, including randomForest, SVM-RFE, and LASSO, to select key NECC specific dysregulated proteins (kNsDEPs). The diagnostic effect of kNsDEPs was validated by a set of predictive models and immunohistochemical staining method. The dysregulation patterns of kNsDEPs were further investigated in other neuroendocrine carcinomas.

Results: Our results showed that NECC displays distinctive biological characteristics, such as HPV18 infection, and exhibits unique molecular features, particularly an enrichment in cytoskeleton-related functions. Furthermore, secretagogin (SCGN), adenylyl cyclase-associated protein 2 (CAP2), and calcyclin-binding protein (CACYBP) were identified as kNsDEPs. These kNsDEPs play a central role in cytoskeleton protein binding and showcase robust diagnostic ability and specificity for NECC. Moreover, the concurrent upregulation of SCGN and CACYBP, along with the downregulation of CAP2, represents a unique feature of NECC, distinguishing it from other neuroendocrine carcinomas.

Conclusions: This study uncovers the significance of kNsDEPs and elucidates their regulated networks in the context of NECC. It highlights the pivotal role of kNsDEPs in NECC diagnosis, thus offering promising prospects for the development of diagnostic biomarkers for NECC.

Background and objective: In clinical practice, CK19 can be an important predictor for the prognosis of HCC. Due to the high incidence and mortality rates of HCC, more effective and practical prognostic prediction models need to be developed urgently.

Methods: A total of 1,168 HCC patients, who underwent radical surgery at the Guangxi Medical University Cancer Hospital, between January 2014 and July 2019, were recruited, and their clinicopathological data were collected. Among the clinicopathological data, the optimal cutoff value of CK19-positive HCC was determined by calculating the area under the curve (AUC) using survival analysis and time-dependent receiver operating characteristic (timeROC) curve analysis. The predictors were screened using univariate and multivariate COX regression and least absolute shrinkage and selection operator (LASSO) regression to construct nomogram prediction models, and their predictive potentials were assessed using calibration curves and AUC values.

Results: The 0% positive rate of CK19 was considered the optimal cutoff value to predict the poor prognosis of CK19-positive HCC. The survival analysis of 335 CK19-positive HCC showed no significant statistical differences in the overall survival (OS) and disease-free survival (DFS) of CK19-positive HCC patients. A five-factor risk (CK19, CA125, Edmondson, BMI, and tumor number) scoring model and an OS nomograph model were constructed and established, and the OS nomograph model showed a good predictive performance and was subsequently verified.

Conclusion: A 0% expression level of CK19 protein may be an optimal threshold for predicting the prognosis of CK19-positive HCC. Based on this, CK19 marker a good nomogram model was constructed to predict HCC prognosis.

Purpose: Pathological nipple discharge (PND) is associated with malignancy. This study aimed to investigate the value of fiberoptic ductoscopy (FDS) and the feasibility of immediate injection of methylene blue after FDS to identify discharging ducts and intraductal lesions without overflow of methylene blue during surgery.

Methods: From May 2019 to December 2023, 164 PND patients were enrolled. Methylene blue was injected into the discharging ducts immediately after FDS. Surgery was underwent several hours later. The dyeing effect and the operation time were assessed. The pathological results were analyzed with clinical characteristics and ductoscopic appearances.

Results: The overall detection rate of malignancy was 14.0% (23/164). Both ultrasound (US) and mammography (MG) were negative in 80 (48.8%) patients, while pathology yielded 10 (12.5%) breast cancers. Statistical analysis revealed that patients exhibiting older age, menopause, positive MG, and bloody discharge had a higher propensity for malignancy (P < 0.05). Ductoscopic features such as multiple and distal lesions, irregular morphology and hemorrhage of the lesions, and roughness and stiffness of the ductal walls were associated with malignancy (P < 0.05). Conducting surgery 12-24 h after injection of methylene blue resulted in optimal dyeing without overflow of methylene blue.

Conclusion: FDS is an effective and feasible examination for PND patients with negative imaging results. Immediate injection of methylene blue after FDS allows clear identification of discharging ducts and intraductal lesions without overflow of methylene blue. This approach may be useful in guiding selective ductectomy for the detection of early breast cancer.

Objective: The goal of this current research was to explore the impact of cancer-related fatigue on the quality of life among patients with cancer, as well as the multiple mediating roles of psychological coherence and stigma.

Methods: This study utilized a cross-sectional design. A questionnaire was administered between November 2022 and May 2023 to 364 patients with cancer in two tertiary hospitals in Jinzhou City, Liaoning Province, China. The questionnaires included the General Information Questionnaire, Cancer-Related Fatigue Questionnaire, Psychological Coherence Scale, Stigma Scale, and Quality of Life Questionnaire. SPSS 25.0 and PROCESS 3.5 macros were used for descriptive statistics and correlation analysis of the data, as well as multiple mediation effect tests.

Results: Cancer-related fatigue directly affects quality of life (β = -0.950, 95% CI = -1.138 to -0.763) and indirectly through three mediators: psychological coherence (β = -0.172, 12.58% of total effect), stigma (β = -0.193, 14.12% of total effect), and both psychological coherence and stigma (β = -0.052, 3.80% of total effect), totaling a 30.50% mediating effect.

Conclusion: Overall, psychological coherence and stigma may play an important mediating role between cancer-related fatigue and quality of life in patients with cancer. This suggests that alleviating cancer-related fatigue, while enhancing psychological coherence and reducing stigma, could be effective strategies for improving patients' quality of life. Therefore, healthcare professionals and related professionals should pay attention to and adopt effective interventions to alleviate cancer-related fatigue, enhance psychological coherence, and reduce stigma, thereby contributing to the overall well-being and quality of life of patients with cancer.

Background: Pancreatic cancer poses a significant challenge in individuals with diabetes, prompting a reevaluation of established risk factors beyond conventional glycemic control measures.

Objectives: To explore the complex interplay of metabolic and psychosocial determinants in pancreatic cancer risk among individuals with diabetes, challenging prevailing perspectives and advocating for a comprehensive approach.

Methods: A total of 21,945 UK Biobank participants with baseline diabetes diagnosis were analyzed. Social isolation was assessed through a questionnaire capturing five factors: household size, social activities, friend/family visits, loneliness, and confiding in others. Incident pancreatic cancer was identified using ICD codes. Baseline characteristics, insulin use, and other relevant factors were analyzed. Hazard ratios and mediation analyses were conducted to determine the relationship between social isolation, inflammation, and pancreatic cancer risk.

Results: Individuals with high social isolation were more likely to be male, smokers, non-drinkers, and have shorter sleep duration. They also had an increased risk of pancreatic cancer (HR = 2.65, 95% CI = 1.12-6.24) compared to those with low social isolation. Mediation analyses highlighted inflammation as a crucial mediator, with the proportion mediated by inflammation being 19.44% for insulin use, 10.34% for smoking, and 8.33% for social isolation.

Conclusions: Our findings highlight the importance of psychosocial factors in pancreatic cancer risk and underscore the need for further research to elucidate the underlying mechanisms.

Objective: This study aimed to investigate the diagnostic potential of serum CXC chemokine ligand 5 (CXCL5) in patients with chronic atrophic gastritis (CAG) and to establish a prediction model for better diagnosis of CAG.

Methods: A retrospective analysis was conducted, encompassing 570 cases of CAG patients admitted to the Department of Gastroenterology of the Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, who underwent gastroscopy and received pathologically confirmed diagnoses between June 2018 and June 2023. Additionally, 570 cases without CAG who underwent health checkups were included and classified into the control group. Single-factor and multi-factorial logistic regression analyses were employed to identify risk factors of CAG, and a prediction model for diagnosing CAG was developed using R software. The predictive performance of the constructed model was verified and evaluated through ROC analysis, decision curve analysis (DCA), and prediction efficacy curve.

Results: Multi-factorial logistic regression analysis revealed that history of smoking, family history of tumurs, Pepsinogen I (PG I), Gastrin 17 (G-17), Helicobacter pylori infection, D-dimer, and CXCL5 were independent risk factors in CAG patients. A nomogram for the diagnosis of CAG was constructed using R software. The ROC curve demonstrated that CXCL5 showed the best predictive efficacy as a single indicator, with an AUC of 0.897, a sensitivity of 0.789, and a specificity of 0.999. Furthermore, the nomogram exhibited an AUC of 0.992, a sensitivity of 0.958, and a specificity of 0.970. Calibration and DCA curves indicated that the predicted values of the nomogram were highly concordant with the observed values, thus demonstrating a high predictive value.

Conclusion: In this study, we found a correlation between serum CXCL5 level and CAG, and developed a prediction model to assist the clinical diagnosis of CAG.

Background: In this study, we retrospectively examined the prognostic significance of the pathological status of esophageal squamous cell carcinoma (ESCC) patients following neoadjuvant chemoradiotherapy (NCRT) and surgery.

Methods: Data of patients with cT2-4aN0-3 stage ESCC who underwent NCRT and esophagectomy during 2014-2022 were reviewed retrospectively. Survival differences were compared according to revised TN (rTN) stage (ypT0N0, ypT + N0, ypT0N+, and ypT + N+) using univariate and Cox regression analyses.

Results: Of the 136 patients (59.1 ± 7.2 y) included in this study, 123 (90.4%) were males. There were 39 (28.7%) patients with ypT0N0 disease, 49 (36.0%) ypT + N0, 11 (8.1%) ypT0N+, and 37 (27.2%) ypT + N+. Additionally, 126 patients had a median follow-up period of 30 (1-90) months. The 5-year overall survival was 81.6% in ypT0N0 group, 53.1% for ypT + N0, 50.0% for ypT0N+, and 18.6% for ypT + N+ (p < 0.001) and 5-year disease-free survival was 70.1% for ypT0N0, 39.7% for ypT + N0, 33.3% for ypT0N+, and 18.4% for ypT + N+ (p < 0.001). The ypT + N0 and ypT0N + groups showed no significant differences in survival (p > 0.05). In Cox regression analysis, ypT stage and rTN stage showed an independent association with OS (p = 0.026 and 0.001, respectively). During the follow-up period, 69 (54.8%) patients developed recurrence, with ypT0N0 patients experiencing fewer local and distant recurrences compared to other groups (p < 0.001).

Conclusion: In ESCC patients, the ypT0N0 status after NCRT predicts prolonged survival, but this reduces significantly when nodal metastases or residual primary lesions are present.

Background: Myelofibrosis (MF) is a clonal haematopoietic disease, with median overall survival for patients with primary MF only 6.5 years. The most frequent gene mutation found in patients is JAK2^V617F, causing constitutive activation of the kinase and activation of downstream signalling. Fedratinib is an oral selective JAK2 inhibitor. It has shown activity in MF and is well-tolerated, but combination with other therapies is likely needed to achieve clonal remission. Combining a JAK2 inhibitor with an interferon may be synergistic, as haematopoietic cells are activated from quiescence (a typical kinase resistance mechanism) rendering them more sensitive to inhibition. Ropeginterferon alfa-2b is a next generation pegylated interferon-α-2b with high tolerability and clinical activity in patients with MF, however, evidence of tolerability and activity in combination with fedratinib is lacking in this setting. The aim of the FEDORA trial is to assess tolerability, safety, and activity of fedratinib with ropeginterferon alfa-2b in patients with MF who require treatment to justify further investigation in a phase III trial.

Methods: FEDORA is a single arm, multicentre, open-label, Bayesian phase II trial to assess tolerability, safety, and activity of fedratinib with ropeginterferon alfa-2b aiming to recruit 30 patients. Patients with JAK2^V617F positive primary or secondary MF, who are aged ≥ 18 years, have intermediate-1 with palpable splenomegaly of > 5cm, intermediate-2, or high-risk disease according to the Dynamic International Prognostic Scoring System (DIPSS), and who require treatment are eligible. The primary outcome is tolerability, whereby the combination is deemed intolerable in a patient if drug-related toxicities in the first four months of treatment lead to: either drug being discontinued; delays in treatment exceeding 28 consecutive days; or death. FEDORA uses a within-patient dose escalation regimen to ensure each patient reaches a personalised dose combination that is acceptable.

Discussion: FEDORA is using a Bayesian trial design and aims to provide evidence of the tolerability, safety, and activity of combining fedratinib with ropeginterferon alfa-2b upon which the decision as to whether a phase III trial is warranted will be based.

Trial registration: EudraCT number: 2021-004056-42.

Isrctn: 88,102,629.