Cancer Biomarkers - Volume 40, issue 2

Authors: Wen, Yixin | Xu, Feng | Zhang, Hui

Article Type: Research Article

Abstract: BACKGROUND: Circular RNAs (circRNAs) perform key regulatory functions in osteosarcoma (OS) tumorigenesis. In this study, we aimed to explore the detailed action mechanisms of circ_0049271 in OS progression. METHODS: Cell colony formation, cell counting kit-8, and transwell assays were performed to assess the proliferation and invasion of OS cells. Quantitative reverse transcription-polymerase chain reaction and western blotting were used to determine the expression levels of polymerase 1 and transcript release factor (PTRF), microRNA (miR)-1197, and circ_0049271 in OS cells. Furthermore, RNA immunoprecipitation and dual luciferase assays were conducted to explore the targeted relationships among PTRF …, miR-1197 , and circ_0049271 . Finally, a tumor formation assay was conducted to determine the effects of circ_0049271 on in vivo tumor growth in mice. RESULTS: High expression levels of miR-1197 and low levels of circ_0049271 and PTRF were observed in OS cells. circ _0049271 targeted miR-1197 to mediate PTRF expression. Moreover, the proliferation and invasion of OS cells were repressed by circ_0049271 or PTRF overexpression and increased by miR-1197 upregulation. Enforced circ_0049271 also impeded tumor growth in vivo . Upregulation of miR-1197 reversed the antitumor effects of circ_0049271 on OS progression in vitro ; however, PTRF overexpression attenuated the cancer-promoting effects of miR-1197 on OS in vitro . CONCLUSIONS: Our findings revealed that circ_0049271 targeted the miR-1197/PTRF axis to attenuate the malignancy of OS, suggesting a potential target for its clinical treatment. Show more

Keywords: Osteosarcoma, circRNA, circ_0049271, miR-1197, PTRF

DOI: 10.3233/CBM-230191

Citation: Cancer Biomarkers, vol. 40, no. 2, pp. 141-153, 2024

Authors: Karamti, Hanen | Alharthi, Raed | Umer, Muhammad | Shaiba, Hadil | Ishaq, Abid | Abuzinadah, Nihal | Alsubai, Shtwai | Ashraf, Imran

Article Type: Research Article

Abstract: Breast cancer is a major cause of female deaths, especially in underdeveloped countries. It can be treated if diagnosed early and chances of survival are high if treated appropriately and timely. For timely and accurate automated diagnosis, machine learning approaches tend to show better results than traditional methods, however, accuracy lacks the desired level. This study proposes the use of an ensemble model to provide accurate detection of breast cancer. The proposed model uses the random forest and support vector classifier along with automatic feature extraction using an optimized convolutional neural network (CNN). Extensive experiments are performed using the original, …as well as, CNN-based features to analyze the performance of the deployed models. Experimental results involving the use of the Wisconsin dataset reveal that CNN-based features provide better results than the original features. It is observed that the proposed model achieves an accuracy of 99.99% for breast cancer detection. Performance comparison with existing state-of-the-art models is also carried out showing the superior performance of the proposed model. Show more

Keywords: Breast cancer detection, image processing, healthcare, machine learning, ensemble learning, deep convoluted features

DOI: 10.3233/CBM-230294

Citation: Cancer Biomarkers, vol. 40, no. 2, pp. 155-170, 2024

Authors: Wang, Tianxiang | Qian, Luxi | Zhang, Pingchuan | Du, Mingyu | Wu, Jing | Peng, Fanyu | Yao, Chengyun | Yin, Rong | Yin, Li | He, Xia

Article Type: Research Article

Abstract: INTRODUCTION: GINS2 exerts a carcinogenic effect in multiple human malignancies, while it is still unclear that the potential roles and underlying mechanisms of GINS2 in HNSCC. METHODS: TCGA database was used to screen out genes with significant differences in expression in HNSCC. Immunohistochemistry and qRT-PCR were used to measure the expression of GINS2 in HNSCC tissues and cells. GINS2 was detected by qRT-PCR or western blot after knockdown or overexpression. Celigo cell counting, MTT, colony formation, and flow cytometric assay were used to check the ability of proliferation and apoptosis. Bioinformatics and microarray were used to …screen out the downstream genes of GINS2. RESULTS: GINS2 in HNSCC tissues and cells was up-regulated, which was correlated with poor prognosis. GINS2 gene expression was successfully inhibited and overexpressed in HNSCC cells. Knockdown of GINS2 could inhibit proliferation and increase apoptosis of cells. Meanwhile, overexpression of GINS2 could enhance cell proliferation and colony formation. Knockdown of RRM2 may inhibit HNSCC cell proliferation, while overexpression of RRM2 rescued the effect of reducing GINS2 expression. CONCLUSION: Our study reported the role of GINS2 in HNSCC for the first time. The results demonstrated that in HNSCC cells, GINS2 promoted proliferation and inhibited apoptosis via altering RRM2 expression. Therefore, GINS2 might play a carcinogen in HNSCC, and become a specific promising therapeutic target. Show more

Keywords: HNSCC, GINS2, RRM2, proliferation, apoptosis

DOI: 10.3233/CBM-230337

Citation: Cancer Biomarkers, vol. 40, no. 2, pp. 171-184, 2024

Authors: Zhu, Liucun | Yuan, Fa | Wang, Xue | Zhu, Rui | Guo, Wenna

Article Type: Research Article

Abstract: Cuproptosis a novel copper-dependent cell death modality, plays a crucial part in the oncogenesis, progression and prognosis of tumors. However, the relationships among DNA-methylation located in cuproptosis-related genes (CRGs), overall survival (OS) and the tumor microenvironment remain undefined. In this study, we systematically assessed the prognostic value of CRG-located DNA-methylation for lower-grade glioma (LGG). Clinical and molecular data were sourced from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We employed Cox hazard regression to examine the associations between CRG-located DNA-methylation and OS, leading to the development of a prognostic signature. Kaplan-Meier survival and time-dependent receiver operating …characteristic (ROC) analyses were utilized to gauge the accuracy of the signature. Gene Set Enrichment Analysis (GSEA) was applied to uncover potential biological functions of differentially expressed genes between high- and low-risk groups. A three CRG-located DNA-methylation prognostic signature was established based on TCGA database and validated in GEO dataset. The 1-year, 3-year, and 5-year area under the curve (AUC) of ROC curves in the TCGA dataset were 0.884, 0.888, and 0.859 while those in the GEO dataset were 0.943, 0.761 and 0.725, respectively. Cox-regression-analyses revealed the risk signature as an independent risk factor for LGG patients. Immunogenomic profiling suggested that the signature was associated with immune infiltration level and immune checkpoints. Functional enrichment analysis indicated differential enrichment in cell differentiation in the hindbrain, ECM receptor interactions, glycolysis and reactive oxygen species pathway across different groups. We developed and verified a novel CRG-located DNA-methylation signature to predict the prognosis in LGG patients. Our findings emphasize the potential clinical implications of CRG-located DNA-methylation indicating that it may serve as a promising therapeutic target for LGG patients. Show more

Keywords: Lower-grade glioma, cuproptosis, DNA-methylation, tumor microenvironment, immune checkpoint inhibitors

DOI: 10.3233/CBM-230341

Citation: Cancer Biomarkers, vol. 40, no. 2, pp. 185-198, 2024

Authors: Horackova, Klara | Vocka, Michal | Lopatova, Sarka | Zemankova, Petra | Kleibl, Zdenek | Soukupova, Jana

Article Type: Research Article

Abstract: BACKGROUND: Ovarian cancer (OC) is mostly diagnosed in advanced stages with high incidence-to-mortality rate. Nevertheless, some patients achieve long-term disease-free survival. However, the prognostic markers have not been well established. OBJECTIVE: The primary objective of this study was to analyse the association of the suggested prognostic marker rs2185379 in PRDM1 with long-term survival in a large independent cohort of advanced OC patients. METHODS: We genotyped 545 well-characterized advanced OC patients. All patients were tested for OC predisposition. The effect of PRDM1 rs2185379 and other monitored clinicopathological and genetic variables on survival …were analysed. RESULTS: The univariate analysis revealed no significant effect of PRDM1 rs2185379 on survival whereas significantly worse prognosis was observed in postmenopausal patients (HR = 2.49; 95%CI 1.90–3.26; p = 4.14 × 10 - 11 ) with mortality linearly increasing with age (HR = 1.05 per year; 95%CI 1.04–1.07; p = 2 × 10 - 6 ), in patients diagnosed with non-high-grade serous OC (HR = 0.44; 95%CI 0.32–0.60; p = 1.95 × 10 - 7 ) and in patients carrying a gBRCA1 pathogenic variant (HR = 0.65; 95%CI 0.48–0.87; p = 4.53 × 10 - 3 ). The multivariate analysis interrogating the effect of PRDM1 rs2185379 with other significant prognostic factors revealed marginal association of PRDM1 rs2185379 with worse survival in postmenopausal women (HR = 1.54; 95%CI 1.01–2.38; p = 0.046). CONCLUSIONS: Unlike age at diagnosis, OC histology or gBRCA1 status, rs2185379 in PRDM1 is unlikely a marker of long-term survival in patients with advance OC. Show more

Keywords: Ovarian cancer, long-term survival, PRDM1, BRCA1, biomarker

DOI: 10.3233/CBM-230358

Citation: Cancer Biomarkers, vol. 40, no. 2, pp. 199-203, 2024

Authors: Xiao, Xuesong | Lv, Xiaofei | Lin, Tianyu | Li, Jianqiao | Wang, Rui | Tian, Shaoping | Liu, Xinyu | Liu, Shiming | Jiang, Huamao | Yue, Dan | Wang, Yong

Article Type: Research Article

Abstract: BACKGROUND: Kidney Renal Clear Cell Carcinoma (KIRC) is a malignant tumor that seriously threatens human health. Rho GTPase-activating protein 4 (ARHGAP4) plays an important role in the occurrence and development of tumors. OBJECTIVE: The purpose of this study was to explore the role of ARHGAP4 in the progression of KIRC and its diagnostic and prognostic value. METHODS: Multiple analytical methods and in vitro cell assays were used to explore the expression of ARHGAP4 and its value in the progression, diagnosis and prognosis of KIRC. The biological function of ARHGAP4 was …studied by GO analysis and KEGG pathway analysis, and then the relationship between ARHGAP4 and immune infiltration was analyzed. RESULTS: The expression of ARHGAP4 was significantly up-regulated in KIRC. We found that the high expression of ARHGAP4 was related to the progression of KIRC and suggested a poor prognosis. Compared with normal tissues, ARHGAP4 had a better diagnostic value in KIRC. The biological function of ARHGAP4 was related to immunity, and its expression was also closely related to tumor immune infiltration and immune checkpoints. CONCLUSIONS: Our study demonstrated that ARHGAP4 may be a biomarker, which is related to the progression, diagnosis and prognosis of KIRC. Its biological functions are related to tumor immune infiltration. Show more

Keywords: Rho GTPase-activating protein 4, KIRC, clinical prognosis, immune cell infiltration, biomarker

DOI: 10.3233/CBM-230388

Citation: Cancer Biomarkers, vol. 40, no. 2, pp. 205-223, 2024

Article Type: Research Article

DOI: 10.3233/CBM-239005

Citation: Cancer Biomarkers, vol. 40, no. 2, pp. 225-225, 2024