Cancer Biomarkers - Volume 36, issue 1

Authors: Yao, Weitao | Hou, Jingyu | Liu, Guoqing | Wu, Fangxing | Yan, Qiang | Guo, Liangyu | Wang, Chuchu

Article Type: Research Article

Abstract: BACKGROUND: LncRNA STK4 antisense RNA 1 (STK4-AS1) has been identified as a potential biomarker associated with multiple cancers. We proposed that STK4-AS1 plays a role in the proliferation of osteosarcoma by regulating the cell cycle. METHODS: We compared the expression of STK4-AS1, p53, and p21 in osteosarcoma vs normal samples in clinical tissues and cell lines. We determined the effect of overexpression and knockdown of STK4-AS1 in p53 expressing osteosarcoma cells U2OS, p53 muted osteosarcoma cells MG63, and osteoblast cells hFOB on p53 and p21 expression and the cell viability. For U2OS and MG63, the cell …cycle was analyzed and the expression of cyclin proteins was determined. We overexpressed p53 or p21 in STK4-AS1 overexpressed cells to explore the association of STK4-AS1 and p53 in U2OS. RESULTS: The STK4-AS1 expression was higher and p53 and p21 expression were lower in osteosarcoma tissue and cells than in their non-cancer counterparts. The expression of STK4-AS1 was negatively correlated with the expression of p53 or p21. Knockdown of STK4-AS1 in U2OS decreased the cell viability, increased cells in the G0/G1 phase, decreased cells in the S and G2/M phase, decreased expression of cyclin A and B, increased p53 and p21, and had no effect on cyclin D and cyclin E, while overexpression of STK4-AS1 did the opposes. Overexpression of p53 or p21 recovered some changes caused by STK4-AS1 overexpression in U2OS. MG63 expressed no p53 and the expression of p21, cyclin A, and cyclin B, cell viability, and cell cycle were not affected by altered STK4-AS1 levels. In hFOB cells, the expression of p53 and p21 was decreased and the cell viability was increased when STK4-AS1 was overexpressed, but they were not affected when STK4-AS1 was knocked down. CONCLUSION: LncRNA STK4-AS1 promoted the cell cycle of osteosarcoma cells by inhibiting p53 expression. Show more

Keywords: STK4-AS1, osteosarcoma, cell cycle, p53 protein

DOI: 10.3233/CBM-210291

Citation: Cancer Biomarkers, vol. 36, no. 1, pp. 1-16, 2023

Authors: Zhang, Lun | Zheng, Jiamin | Ismond, Kathleen P. | MacKay, Scott | LeVatte, Marcia | Constable, Jeremy | Isaac Alatise, Olusegun | Peter Kingham, T. | Wishart, David S.

Article Type: Research Article

Abstract: BACKGROUND: African colorectal cancer (CRC) rates are rising rapidly. A low-cost CRC screening approach is needed to identify CRC from non-CRC patients who should be sent for colonoscopy (a scarcity in Africa). OBJECTIVE: To identify urinary metabolite biomarkers that, combined with easy-to-measure clinical variables, would identify patients that should be further screened for CRC by colonoscopy. Ideal metabolites would be water-soluble and easily translated into a sensitive, low-cost point-of-care (POC) test. METHODS: Liquid-chromatography mass spectrometry (LC-MS/MS) was used to quantify 142 metabolites in spot urine samples from 514 Nigerian CRC patients and healthy controls. …Metabolite concentration data and clinical characteristics were used to determine optimal sets of biomarkers for identifying CRC from non-CRC subjects. RESULTS: Our statistical analysis identified N 1 , N 12 -diacetylspermine, hippurate, p -hydroxyhippurate, and glutamate as the best metabolites to discriminate CRC patients via POC screening. Logistic regression modeling using these metabolites plus clinical data achieved an area under the receiver-operator characteristic (AUCs) curves of 89.2% for the discovery set, and 89.7% for a separate validation set. CONCLUSIONS: Effective urinary biomarkers for CRC screening do exist. These results could be transferred into a simple, POC urinary test for screening CRC patients in Africa. Show more

Keywords: Colorectal cancer screening, cancer biomarkers, urine test, liquid chromatography-mass spectrometry, metabolomic profiling, logistic regression

DOI: 10.3233/CBM-220034

Citation: Cancer Biomarkers, vol. 36, no. 1, pp. 17-30, 2023

Authors: Gupta, Amit Kumar | Kumar, Manoj

Article Type: Research Article

Abstract: BACKGROUND: Persistent infection of high-risk HPVs is known to cause diverse carcinomas, mainly cervical, oropharyngeal, penile, etc. However, efficient treatment is still lacking. OBJECTIVE: Identify and analyze potential therapeutic targets involved in HPV oncogenesis and repurposing drug candidates. METHODS: Integrative analyses were performed on the compendium of 1887 HPV infection-associated or integration-driven disrupted genes cataloged from the Open Targets Platform and HPVbase resource. Potential target genes are prioritized using STRING, Cytoscape, cytoHubba, and MCODE. Gene ontology and KEGG pathway enrichment analysis are performed. Further, TCGA cancer genomic data of CESC and HNSCC is …analyzed. Moreover, regulatory networks are also deduced by employing NetworkAnalyst. RESULTS: We have implemented a unique approach for identifying and prioritizing druggable targets and repurposing drug candidates against HPV oncogenesis. Overall, hundred key genes with 44 core targets were prioritized with transcription factors (TFs) and microRNAs (miRNAs) regulators pertinent to HPV pathogenesis. Genomic alteration profiling further substantiated our findings. Among identified druggable targets, TP53 , NOTCH1 , PIK3CA , EP300 , CREBBP , EGFR , ERBB2 , PTEN , and FN1 are frequently mutated in CESC and HNSCC. Furthermore, PIK3CA , CCND1 , RFC4 , KAT5 , MYC , PTK2 , EGFR , and ERBB2 show significant copy number gain, and FN1 , CHEK1 , CUL1 , EZH2 , NRAS , and H2AFX was marked for the substantial copy number loss in both carcinomas. Likewise, under-explored relevant regulators, i.e., TFs (HINFP, ARID3A, NFATC2, NKX3-2, EN1) and miRNAs (has-mir-98-5p, has-mir-24-3p, has-mir-192-5p, has-mir-519d-3p) is also identified. CONCLUSIONS: We have identified potential therapeutic targets, transcriptional and post-transcriptional regulators to explicate HPV pathogenesis as well as potential repurposing drug candidates. This study would aid in biomarker and drug discovery against HPV-mediated carcinoma. Show more

Keywords: HPVs, oncogenesis, therapeutic targets, cervical cancer, HNSCC, TCGA, repurposed drugs

DOI: 10.3233/CBM-210413

Citation: Cancer Biomarkers, vol. 36, no. 1, pp. 31-52, 2023

Authors: Tan, Wei-Qiang | Yuan, Li | Cao, Xu | Wu, Xiao-Yuan | Xing, Yi-Qun | Ye, Ming

Article Type: Research Article

Abstract: BACKGROUND: Long non-coding RNA (LncRNA) TUG1 plays a critical role in the development of human cancers. This study explored whether TUG1 is involved in the cytotoxicity of dendritic cells and cytokine-induced killer cells (DCs-CIK), an immunotherapy approach, in neuroblastoma. METHODS: A TUG1 expression plasmid was transfected into DCs. Neuroblastoma SK-N-SH cells were incubated with CIK cells, DCs-CIK cells, and TUG1-overexpressing DCs-CIK cells, with or without irradiation. SK-N-SH cell viability, colony formation, migration, and apoptosis were analyzed using CCK-8, colony formation assay, transwell assay, and flow cytometry, respectively. Production of IL-12, IL-2 and IFN-γ …in the supernatants was determined using ELISA. A dual luciferase activity assay was performed to confirm the molecular interactions between TUG1 and miR-204. Tumor-bearing mice were established by injection of SK-N-SH cells followed by stimulation with CIK cells, DC-CIK cells, and TUG1-overexpressing DCs-CIK cells. RESULTS: Compared to CIK alone or DC-CIK therapy, overexpression of TUG1 significantly suppressed tumor cell proliferation, colony formation, and migration of neuroblastoma cells. Moreover, upregulation of TUG1 robustly induced apoptosis and altered key molecules associated with apoptosis and epithelial-mesenchymal transition. Contents of IL-12, IL-2 and IFN-γ were dramatically elevated in the supernatants in the coculturing system upon transfection with TUG1. In addition, TUG1 was found to be act as miR-204 sponge. Furthermore, in vivo experiments demonstrated that upregulation of TUG1 potentiated the antitumor activity of DC-CIK immunotherapy. CONCLUSION: Overexpression of TUG1 promotes DC maturation and enhances CIK cytotoxicity, suggesting that TUG1 may be a novel target for enhancing DC-CIK based immunotherapy for neuroblastoma. Show more

Keywords: Neuroblastoma, immunotherapy, lncRNA TUG1

DOI: 10.3233/CBM-210436

Citation: Cancer Biomarkers, vol. 36, no. 1, pp. 53-61, 2023

Authors: Borg, Morten | Nederby, Line | Wen, Sara Witting Christensen | Hansen, Torben Frøstrup | Jakobsen, Anders | Andersen, Rikke Fredslund | Weinreich, Ulla Møller | Hilberg, Ole

Article Type: Research Article

Abstract: BACKGROUND: There is an urgent need for early detection of lung cancer. Screening with low-dose computed tomography (LDCT) is now implemented in the US. Supplementary use of a lung cancer biomarker with high specificity is desirable. OBJECTIVE: To assess the diagnostic properties of a biomarker panel consisting of cytokeratin 19 fragment (CYFRA 21-1), carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125). METHODS: A cohort of 250 high-risk patients was investigated on suspicion of lung cancer. Ahead of diagnostic work-up, blood samples taken. Cross-validated prediction models were computed to assess lung cancer detection properties. …RESULTS: In total 32% (79/250) of patients were diagnosed with lung cancer. Area under the curve (AUC) for the three biomarkers was of 0.795, with sensitivity/specificity of 57%/93% and negative predictive value of 83%. When combining the biomarkers with US screening criteria, the AUC was 0.809, while applying only US screening criteria on the cohort, yielded an AUC of 0.62. The ability of the biomarkers to detect stage I-II lung cancer was substantially lower; AUC 0.54. CONCLUSIONS: In a high-risk cohort, the detection properties of the three biomarkers were acceptable compared to current LDCT screening criteria. However, the ability to detect early stage lung cancer was low. Show more

Keywords: Lung cancer, screening, biomarkers, cytokeratin 19 fragment (CYFRA 21-1), carcinoembryonic antigen (CEA), cancer antigen 125 (CA125)

DOI: 10.3233/CBM-210543

Citation: Cancer Biomarkers, vol. 36, no. 1, pp. 63-69, 2023

Authors: Incharoen, Pimpin | Jinawath, Artit | Arsa, Lalida | Kamprerasart, Kaettipong | Trachu, Narumol | Monnamo, Nanamon | Khiewngam, Khantong | Muntham, Dittapol | Chansriwong, Phichai | Sirachainan, Ekaphop | Reungwetwattana, Thanyanan

Article Type: Research Article

Abstract: BACKGROUND: Information on genetic alterations, notably EGFR mutations, is important for guiding non-small-cell lung cancer (NSCLC) treatment. Circulating tumor DNA (ctDNA) analysis represents a less invasive alternative to tissue biopsy for analyzing mutation status, but its clinical value may vary across disease stages. OBJECTIVE: To explore clinical correlates of ctDNA and tissue/plasma-based EGFR mutation (EGFRm ) status across all NSCLC stages. METHODS: Ninety patients were analyzed, representing three cohorts: newly-diagnosed early-stage, advanced-stage, and recurrent NSCLC. Relationships among clinical/surgical parameters, ctDNA, EGFRm status, and survival outcomes were analyzed. RESULTS: …Plasma/tissue EGFRm concordance was lower in early-stage (58.6%) than in advanced-stage patients (87.5%). In early-stage patients, ctDNA levels were variable and not significantly associated with clinical/surgical parameters. In advanced-stage patients, time to EGFR-TKI treatment failure (TTF), but not overall survival (OS), was significantly longer in EGFRm -positive vs. EGFRm -negative patients. In patients with recurrent disease, 40% of plasma samples were EGFR T790M -positive at recurrence. In T790M -positive patients, we noted slight trends toward longer OS with vs. without osimertinib treatment and longer OS and TTF with second-line vs. later-line osimertinib. CONCLUSIONS: Our results affirm the use of ctDNA testing in advanced-stage and recurrent NSCLC. Further studies on osimertinib as early-line therapy, clinical correlates and the utility of plasma-based testing in early-stage NSCLC are warranted. Show more

Keywords: Circulating tumor DNA, mutation, mutation, osimertinib, pulmonary adenocarcinoma

DOI: 10.3233/CBM-220079

Citation: Cancer Biomarkers, vol. 36, no. 1, pp. 71-82, 2023

Authors: Wu, Mengni | Lu, Linlin | Dai, Tiantian | Li, Aoshuang | Yu, Yue | Li, Yadi | Xu, Zhihua | Chen, Yan

Article Type: Research Article

Abstract: Breast cancer (BC) is the most common cancer among women and a leading cause of cancer-related deaths worldwide. The diagnosis of early patients and the prognosis of advanced patients have not improved over the past several decades. The purpose of the present study was to identify the lncRNA-related genes based on ceRNA network and construct a credible model for prognosis in BC. Based on The Cancer Genome Atlas (TCGA) database, prognosis-related differently expressed genes (DEGs) and a lncRNA-associated ceRNA regulatory network were obtained in BC. The patients were randomly divided into a training group and a testing group. A ceRNA-related …prognostic model as well as a nomogram was constructed for further study. A total of 844 DElncRNAs, 206 DEmiRNAs and 3295 DEmRNAs were extracted in BC, and 12 RNAs (HOTAIR, AC055854.1, ST8SIA6-AS1, AC105999.2, hsa-miR-1258, hsa-miR-7705, hsa-miR-3662, hsa-miR-4501, CCNB1, UHRF1, SPC24 and SHCBP1) among them were recognized for the construction of a prognostic risk model. Patients were then assigned to high-risk and low-risk groups according to the risk score. The Kaplan-Meier (K-M) analysis demonstrated that the high-risk group was closely associated with poor prognosis. The predictive nomogram combined with clinical features showed performance in clinical practice. In a nutshell, our ceRNA-related gene model and the nomogram graph are accurate and reliable tools for predicting prognostic outcomes of BC patients, and may make great contributions to modern precise medicine. Show more

Keywords: Breast cancer, ceRNA, prognosis, risk model, nomogram

DOI: 10.3233/CBM-210545

Citation: Cancer Biomarkers, vol. 36, no. 1, pp. 83-96, 2023

Article Type: Retraction

DOI: 10.3233/CBM-229008

Citation: Cancer Biomarkers, vol. 36, no. 1, pp. 97-97, 2023

Article Type: Retraction

DOI: 10.3233/CBM-229009

Citation: Cancer Biomarkers, vol. 36, no. 1, pp. 99-99, 2023

Article Type: Retraction

DOI: 10.3233/CBM-229010

Citation: Cancer Biomarkers, vol. 36, no. 1, pp. 101-101, 2023