Translational cancer research最新文献

Background: Pediatric nephroblastoma is the most common abdominal malignancy in children. Hyperfibrinogenemia and thrombocytosis are often associated with malignancy and poor prognosis. This study aimed to investigate the relationship between high fibrinogen and platelet levels and the clinicopathologic features as well as overall survival in pediatric nephroblastoma.

Methods: We recruited a total of 129 nephroblastoma patients in this research. The patients were evaluated retrospectively using the Kaplan-Meier method and Log rank test to investigate the correlation between patient survival and fibrinogen and platelet levels. A multivariate Cox regression model and a predictive nomogram have also been constructed.

Results: Our findings indicated that fibrinogen levels were associated with Children's Oncology Group (COG) stage (P<0.001), pathological typing (P<0.001), hematuresis (P=0.002), hypertension (P=0.02), and venous thrombosis (P<0.001). Platelet levels were associated with COG stage (P<0.001), pathological typing (P<0.001), hematuresis (P=0.001), and venous thrombosis (P<0.001). Elevated fibrinogen and platelet levels are associated with poor overall survival (P<0.001). Multivariate analysis also indicated that elevated fibrinogen and platelet were independent risk factors (P=0.02, and P<0.001). The nomogram model demonstrates its application value in predicting the prognosis of pediatric nephroblastoma. The calibration curve validates that the predictions made by the nomogram model are in agreement with the actual observed survival outcomes.

Conclusions: High levels of platelets and fibrinogen may have negative effects on the prognosis of children with nephroblastoma.

Background: Early detection for colorectal cancer (CRC) can enhance the patient prognosis. We aimed to validate the combined multi-gene detection in plasma of Septin9, SDC2, KCNQ5, and IKZF1 for early diagnosing of CRC in this prospective study.

Methods: Overall, 124 participants including 45 CRC patients, 8 advanced adenoma patients, 34 small polyp patients, and 37 normal controls who underwent colonoscopy were enrolled. The carcinoembryonic antigen (CEA) test and methylation tests for Septin9, SDC2, KCNQ5, and IKZF1 were performed. Sensitivity, specificity, and the area under the curve (AUC) of the receiver operating characteristic (ROC) curve were utilized to evaluate the diagnostic value of each biomarker. Additionally, the association between the positive rates of methylated Septin9, SDC2, KCNQ5, and IKZF1 and the clinicopathological characteristics of CRC was also analyzed.

Results: The positive detection rate of multi-gene methylation in CRC patients was 86.67%, for stage I and stage II patients, the positive rates were 90.91% and 87.50%, both of which were significantly higher than CEA, which had rates of 55.56%, 18.18% and 56.25% for the corresponding stages. In patients with advanced adenomas and small polyps, the positive rates for the four-gene combined test were 62.50% and 52.94%, respectively, which were markedly higher than the CEA rates of 12.50% and 14.71%. AUC of the ROC curve indicated that the diagnostic value of the multi-gene test for CRC was superior to that of any single gene. Correlation analysis revealed that the positive rate of the test was not affected by patients' clinicopathological characteristics.

Conclusions: A combination of methylated Septin9, SDC2, KCNQ5, and IKZF1 test has the potential for early diagnosis of CRC patients, advanced adenoma patients, and small polyp patients.

Background: Multiple studies suggest a plausible connection between urologic cancers and branched-chain amino acids (BCAAs) breakdown metabolic enzymes. Nevertheless, there is scarce exploration into the variations in circulating BCAAs. In our research, we utilize bidirectional, two-sample Mendelian randomization (MR) analysis to predict the link between BCAAs levels and three distinct types of urological tumors.

Methods: The study examined data from the UK Biobank, including a comprehensive genome-wide association study (GWAS) of total BCAAs, leucine, isoleucine, and valine, alongside three urological system tumors [prostate cancer (PCa), kidney cancer, and bladder cancer] sourced from the Medical Research Council Integrative Epidemiology Unit (MRC-IEU) and FinnGen Consortium databases. The primary analytical approach involved the use of the inverse variance weighted (IVW) method, complemented by MR-PRESSO global testing and MR-Egger regression to identify potential horizontal pleiotropy. Heterogeneity was evaluated using the Cochran Q test.

Results: The levels of circulating total BCAAs [odds ratio (OR) =1.002688, 95% confidence interval (CI): 1.000, 1.005, P=0.03], leucine (OR =1.0038, 95% CI: 1.001, 1.007, P=0.008), isoleucine (OR =1.003352, 95% CI: 1.000, 1.007, P=0.04), and valine (OR =1.00279, 95% CI: 1.001, 1.005, P=0.009) showed positive associations with PCa risk. However, there was inadequate evidence to establish a link between BCAAs and bladder or kidney cancer.

Conclusions: In summary, an association existed between elevated levels of circulating total BCAAs, leucine, isoleucine, and valine, and an increased risk of PCa. However, no correlation was detected between BCAAs and kidney or bladder cancer.

Background: Numerous studies have demonstrated that immune cell infiltration is a significant predictor in the prognosis of those with breast cancer. This study aimed to develop a prognostic model for undifferentiated breast cancer using immune-related markers.

Methods: Differentially expressed genes (DEGs) and prognostic factors were identified from The Cancer Genome Atlas (TCGA) database. Cancer immune-associated genes were filtered using the GeneCards database. Least absolute shrinkage and selection operator (LASSO) and Cox proportional hazards regression were employed to select prognostic indicators. The single-sample gene set enrichment analysis (ssGSEA) algorithm and the CIBERSORT algorithm were used to analyze the correlation of prognostic indicators with immune cells in breast cancer.

Results: We identified six tumor immune-related genes, including zic family member 2 (ZIC2), solute carrier family 7 member 5 (SLC7A5), forkhead box J1 (FOXJ1), C-X-C motif chemokine ligand 9 (CXCL9), tumor necrosis factor receptor superfamily member 18 (TNFRSF18), and serine protease 2 (PRSS2), for the development of a prognostic model for patients with breast cancer. Notably, the results of the correlation analysis indicated that CXCL9 was associated with antitumor immune cells, including CD8⁺ T cells, cytotoxic cells, M1 macrophages, and activated memory CD4 T cells, and with the enrichment of natural killer (NK) CD56dim cells. Furthermore, CXCL9 exhibited a significant negative association with the tumor-promoting M2 macrophage phenotype.

Conclusions: Our study established a six-gene model for predicting breast cancer prognosis. Furthermore, we unexpectedly discovered that CXCL9 is integral to immune infiltration in breast cancer and may serve as a critical biomarker for evaluating immune response and therapeutic efficacy in breast cancer treatment.

Background: The persistently high mortality and morbidity rates of hepatocellular carcinoma (HCC) remain a global concern. Notably, the disruptions in mitochondrial cholesterol metabolism (MCM) play a pivotal role in the progression and development of HCC, underscoring the significance of this metabolic pathway in the disease's etiology. The purpose of this research was to investigate genes associated with MCM and develop a model for predicting the prognostic features of patients with HCC.

Methods: MCM-related genes (MCMGs) were identified through The Cancer Genome Atlas (TCGA), The Molecular Signatures Database (MsigDB), and the Mitocarta3.0 databases. Differential gene expression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression analysis were performed using R software to construct a MCM-related model. This model underwent further analysis for somatic mutations, single sample gene set enrichment analysis (ssGSEA), stromal and immune cell estimation, immune checkpoint evaluation, and drug susceptibility prediction to assess the tumor microenvironment (TME) and therapeutic responses. The mRNA expression levels of the genes associated with the model were quantified using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR).

Results: The model, which included six MCMGs (ACADL, ACLY, TXNRD1, DTYMK, ACAT1, and FLAD1), divided all patients (age ≤65 vs. >65 years, P<0.001; male vs. female, ns) into a high-risk group and a low-risk group. The high-risk group showed a higher mortality rate and lower survival rate with AUC of 0.785, 0.752, 0.756, 0.774 and 0.759 for the 1-, 2-, 3-, 4-, and 5-year respectively. A nomogram based on risk score, stage, T, and M had a better prognostic accuracy, with AUC of 0.808, 0.796, 0.811, 0.824 and 0.795 for the 1-, 2-, 3-, 4-, and 5-year respectively. The high-risk group showed enrichment in cell cycle, cell division, and chromosome processes, and a significantly higher tumor mutation burden (TMB) value compared to the low-risk group. Further immune infiltration analysis indicated a significantly reduction in the abundances of some immune cells (activated CD4 T cells, type 2 helper T cells, and neutrophils) and significantly higher expression levels of some immune checkpoint (CD80, CTLA4, HAVCR2, and TNFRSF4) in the high-risk group. Moreover, the risk score was associated with the response to immune checkpoint inhibitors (ICIs) therapy and efficiencies of multiple chemotherapy drugs.

Conclusions: This study developed a prognostic model based on MCMGs, which can predict the prognosis of liver cancer patients and their response to immunotherapy and chemotherapy. The model may provide new strategies to enhance the prognosis and treatment of HCC.

Background: Neurofibromatosis type 1 (NF-1), a rare autosomal dominant disorder, arises from NF1 gene mutations affecting neurofibromin, a Ras GTPase regulator. These mutations activate Ras proteins, triggering clinical symptoms such as skin spots, epilepsy, pain, and tumors. Although gastrointestinal stromal tumors are well-known in NF-1, diffuse intestinal ganglioneuromatosis remains an extremely rare complication.

Case description: This paper reports a case of a 23-year-old male patient with NF1 who underwent a right hemicolectomy due to a cecal mass. Pathological findings were consistent with diffuse intestinal ganglioneuromatosis. Eight months after the surgery, the patient underwent an amputation due to the progressive enlargement of a tumor in his right lower limb, which had been present for 20 years. Pathological results confirmed NF1. Due to the high likelihood of tumor recurrence if only the mass in the right lower limb were to be resected, a surgery involving the amputation of the right lower limb along with the tumor removal was ultimately performed, followed by the installation of a prosthesis postoperatively. To date, the tumor has not recurred. However, due to psychological or skeletal developmental issues, the patient has not regained the ability to walk.

Conclusions: This case represents a rare occurrence of neurofibromatosis accompanied by diffuse intestinal ganglioneuromatosis. The discovery and reporting of this rare case enhance the clinical understanding of neurofibromatosis (particularly in terms of uncommon complications) and enrich the clinical spectrum of neurofibromatosis and its complications, offering new insights and approaches for future treatment of similar cases.

Background: Primary choriocarcinoma of the pulmonary artery is an exceedingly rare malignant neoplasm, which is often misdiagnosed due to its nonspecific clinical presentation. While this condition is characterized by the presence of trophoblastic cells, typically associated with gestational trophoblastic diseases, we encountered a case occurring in an extragenital location. The rarity of such tumors makes it challenging for clinicians to consider them in differential diagnosis, especially when the initial symptoms mimic more common conditions such as pulmonary thromboembolism (PTE).

Case description: We present a clinical case of a 32-year-old female with suspected PTE, attributed to severe cough, hemoptysis, chest pain, oral contraceptive use, and a pulmonary artery filling defect observed on computed tomography pulmonary angiography (CTPA). The patient was treated with standard anticoagulation therapy; however, there was no improvement in the clinical condition. A biopsy was subsequently performed, leading to the histopathologic diagnosis of primary pulmonary artery choriocarcinoma with the presence of malignant trophoblastic cells within the pulmonary artery. The patient underwent chemotherapy and achieved complete remission within a 1-year follow-up period, as confirmed by β-human chorionic gonadotropin (β-HCG) tests and imaging examinations showing marked improvement.

Conclusions: This case underscores the importance of early recognition and accurate diagnosis of primary pulmonary artery choriocarcinoma, a condition that can be easily overlooked due to its rarity and deceptive clinical presentation. Timely diagnosis is crucial for the initiation of appropriate treatment, such as chemotherapy, which in this instance, contributed to the patient's survival. This report highlights the need for heightened clinical suspicion and the use of invasive diagnostic procedures in cases where the clinical picture is atypical and does not respond to standard therapeutic interventions.