Cancer Biomarkers - Volume 37, issue 2

Authors: Li, Jiajia | Wang, Zhenpeng | Liu, Wenjie | Tan, Linsheng | Yu, Yunhe | Liu, Dongzhen | Wei, Zhentong | Zhang, Songling

Article Type: Research Article

Abstract: BACKGROUND: Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancies. The poor prognosis of EOC is mainly due to its asymptomatic early stage, lack of effective screening methods, and a late diagnosis in the advanced stages of the disease. OBJECTIVE: This study investigated metabolomic abnormalities in epithelial ovarian cancers. METHODS: Our study developed a novel strategy to rapidly identify the metabolic biomarkers in the plasma of the EOC patients using Internal Extraction Electrospray Ionization Mass Spectrometry (IEESI-MS) and Liquid Chromatography-mass Spectrometry (HPLC-MS), which could distinguish the differential metabolites in …between plasma samples collected from 98 patients with epithelial ovarian cancer, including 78 cases with original (P), and 20 cases with self-configuration (ZP), as well as 60 healthy subjects, including 30 cases in the original sample (H), 30 cases in self-configuration (ZH), and 6 cases in a blind sample (B). RESULTS: Our study detected 880 metabolites based on criteria variable importance in projection (VIP) > 1, among which 26 metabolites were selected for further identification. They are mainly metabolism-related lipids, amino acids, nucleic acids, and others. The metabolic pathways associated with the differential metabolites were explored by the KEGG analysis, a comprehensive database that integrates genome, chemistry, and system function information. The abnormal metabolites of EOC patients identified by IEESI-MS and HPLC-MS included Lysophosphatidylcholine (16:0) [Lyso PC (16:0)], L-Phenylalanine, L-Leucine, Phenylpyruvic acid, L-Tryptophan, and L-Histidine. CONCLUSIONS: Identifying the abnormal metabolites of EOC patients through metabolomics analyses could provide a new strategy to identify valuable potential biomarkers for the screening and early diagnosis of EOC. Show more

Keywords: Epithelial ovarian cancer, biomarkers, IEESI-MS, HPLC-MS, metabolites

DOI: 10.3233/CBM-220250

Citation: Cancer Biomarkers, vol. 37, no. 2, pp. 67-84, 2023

Authors: Wang, Chien-Wei | Hanson, Eliza K. | Minkoff, Lisa | Whelan, Rebecca J.

Article Type: Research Article

Abstract: BACKGROUND: Despite its importance in the clinical management of ovarian cancer, the CA125 biomarker – located on the mucin protein MUC16 – is still not completely understood. Questions remain about MUC16’s function and structure, specifically the identity and location of the CA125 epitopes. OBJECTIVE: The goal of this study was to characterize the interaction of individual recombinant repeats from the tandem repeat domain of MUC16 with antibodies used in the clinical CA125 II test. METHODS: Using E. coli expression, we isolated nine repeats from the putative antigenic domain of CA125. Amino acid …composition of recombinant repeats was confirmed by high-resolution mass spectrometry. We characterized the binding of four antibodies – OC125, M11, “OC125-like,” and “M11-like” – to nine recombinant repeats using Western blotting, indirect enzyme-linked immunosorbent assay (ELISA), and localized surface plasmon resonance (SPR) spectroscopy. RESULTS: Each recombinant repeat was recognized by a different combination of CA125 antibodies. OC125 and “OC125-like” antibodies did not bind the same set of recombinant repeats, nor did M11 and “M11-like” antibodies. CONCLUSIONS: Characterization of the interactions between MUC16 recombinant repeats and CA125 antibodies will contribute to ongoing efforts to identify the CA125 epitopes and improve our understanding of this important biomarker. Show more

Keywords: CA125, MUC16, ovarian cancer, tandem repeats, antibodies, affinity

DOI: 10.3233/CBM-220191

Citation: Cancer Biomarkers, vol. 37, no. 2, pp. 85-94, 2023

Authors: Xiang, Xuebao | Guo, Yi | Chen, Zhongyuan | Zhang, Fangxin | Qin, Yan

Article Type: Research Article

Abstract: INTRODUCTION: Ferroptosis is a recently discovered type of programmed cell death that plays a crucial role in tumor occurrence and progression. However, no prognostic model has been established yet for clear cell renal cell carcinoma (ccRCC) using ferroptosis-related long non-coding RNAs (lncRNAs). METHODS: In the present study, lncRNA expression profiles, sex, age, TMN stage, and other clinical data of ccRCC samples were extracted from The Cancer Genome Atlas database. In addition, ferroptosis-related lncRNAs were identified using co-expression analysis, and the risk model was established using Cox regression and least absolute shrinkage and selection operator regression analyses. …Log-rank test and Kaplan-Meier analysis were performed to evaluate the predictive accuracy of the risk model for the overall survival (OS) of patients with ccRCC. Moreover, the functional enrichment of ferroptosis-related lncRNAs was performed and visualized using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. RESULTS: Eight prognostic ferroptosis-related lncRNAs were identified, such as LINC01615, AC026401.3, LINC00944, AL590094.1, DLGAP1-AS2, AC016773.1, AC147651.1, and AP000439.2, making up the ferroptosis-related lncRNA risk model. The risk model effectively divided patients with ccRCC into high- and low-risk groups, and their survival time was calculated. The high-risk group showed significantly shorter OS compared to the low-risk group. The nomogram to predict the survival rate of the patients revealed that the risk score was the most critical factor affecting OS in patients with ccRCC. The ferroptosis-related lncRNA risk model was an independent predictor of prognostic risk assessment in patients with ccRCC. CONCLUSION: The ferroptosis-related lncRNAs risk model and genomic clinicopathological nomogram have the potential to accurately predict the prognosis of patients with ccRCC and could serve as potential therapeutic targets in the future. Show more

Keywords: Survival model, ferroptosis, gene signature, urologic neoplasms, bioinformatics, TCGA

DOI: 10.3233/CBM-210445

Citation: Cancer Biomarkers, vol. 37, no. 2, pp. 95-107, 2023

Authors: Thokerunga, Erick | Huang, Fangfang | Bongolo, Christian Cedric | Rugera, Simon Peter | Akankwatsa, Gilbert | Tu, Jian-Cheng

Article Type: Research Article

Abstract: BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related deaths world over. Early diagnosis and effective treatment monitoring significantly improves patients’ outcomes. FKBP11 gene is highly expressed in HCC and could play a role in its development, early diagnosis and treatment. OBJECTIVE: This study aimed to evaluate the expression of FKBP11 in HCC, its correlation with patients’ clinical characteristics and potential role in HCC development. METHODS: Expression was determined by bioinformatics analysis, quantitative real-time PCR, western blot, and immunohistochemistry. CCK-8, Transwell and wound healing assays were used to investigate …involvement in HCC development. RESULTS: FKBP11 was significantly upregulated in HCC cells, tissues and blood (all p < 0.001). Its receiver operator characteristic (ROC) curve had an AUC of 0.864 (95% CI: 0.823–0.904), at a sensitivity of 0.86 and specificity of 0.78 indicating a good diagnostic potential in HCC. Its expression was markedly reduced after surgery (p < 0.0001), indicating a potential application in HCC treatment follow-up. Knockdown of FKBP11 in HCC cells attenuated proliferation and migration, suggesting a possible role in HCC pathogenesis. CONCLUSION: This study thus found that FKBP11 is upregulated in HCC, and the upregulation promotes HCC development. FKBP11 levels are significantly reduced post-surgery and could be a potential diagnostic and prognostic marker for HCC. Show more

Keywords: FKBP11, biomarker, diagnosis, hepatitis B virus, hepatocellular carcinoma

DOI: 10.3233/CBM-220440

Citation: Cancer Biomarkers, vol. 37, no. 2, pp. 109-120, 2023

Authors: Liu, Yu | Yu, Haitao | Zeng, Bin | Gou, Xin | Ren, Ke | Yuan, Fangchao

Article Type: Research Article

Abstract: BACKGROUND: MicroRNAs have been proven to be key molecules in human malignancy. However, to our knowledge, there is no study reporting miR-383-5p expression level and the role it plays in bladder cancer (BC). METHODS: We identified miR-383-5p to be one of the tumor-suppressing genes through using data from The Cancer Genome Atlas (TCGA) and GEO database. We evaluate the expression and activity of miR-383-5p in both BC tissue and cell lines. The impacts of miR-383-5p on proliferative, migratory ability and apoptotic rate in BC cell were evaluated by utilizing CCK-8 kits, flow cytometry, and Transwell assays. …qRT-PCR, western blot, and luciferase reporter assays have been adopted to investigate the underlying mechanisms. In vivo tumorigenicity testing was conducted to determine the impact of miR-383-5p on BC cellular proliferative capacity. RESULTS: Reduced miR-383-5p expression has been determined in BC tissue than in normal bladder tissue. Furthermore, BC cell proliferative, migratory ability was inhibited while apoptosis enhanced in vitro and in vivo by miR-383-5p up-regulation. In vitro and in vivo , silencing miR-383-5p considerably improved the growth and invasive capacity of cell, while decreased the apoptotic rates of BC cells. CONCLUSION: miR-383-5p plays its role as a tumor-suppressing gene by suppressing the PI3K/AKT signaling, hence preventing the development of BC. Show more

Keywords: miR-383-5p, PI3KR1, AKT, bladder cancer

DOI: 10.3233/CBM-220379

Citation: Cancer Biomarkers, vol. 37, no. 2, pp. 121-131, 2023