Cancer Biomarkers - Volume 39, issue 2

Authors: Jiang, Xinyu | Lin, Juli | Zhu, Zhanlin

Article Type: Research Article

Abstract: BACKGROUND: Long-chain noncoding RNA (lncRNA), LINC01569, is important for regulating the extracellular matrix, which affects cell migration. However, its involvement in the occurrence and development of triple-negative breast cancer (TNBC) remains unclear. OBJECTIVE: This study is aimed to investigate the role of LINC01569 on TNBC. METHODS: Online database was used for clinical data analysis. Cell viability and migration capability were monitored using cell counting kit-8 and transwell assays, respectively. Luciferase reporter assay and RNA pull-down were used to confirm the binding capability between noncoding RNAs and filamin A-interacting protein 1-like (FILIP1L). Western blotting was …used to determine the protein content. RESULTS: Compared with normal breast tissue, LINC01569 was significantly reduced in patients with TNBC subtype, and LINC01569 expression gradually decreased with the progression of tumor stage. Patients with TNBC with high lncRNA LINC01569 levels had a better prognosis than did patients with low LINC01569 levels. LINC01569 overexpression inhibited the migration capability, whereas siRNA-mediated LINC01569 downregulation promoted the migration capability in TNBC cells. Using ENCORI and lncRNA SNP online databases, miR-300 was screened as the potential sponge of LINC01569. The binding of LINC01569 to miR-300 was confirmed using the dual-luciferase reporter and RNA pull-down assays. miR-300 was negatively correlated with LINC01569, and miR-300 mimics eliminated the anti-proliferation and anti-migration effects of LINC01569 on TNBC cells. Additionally, FILIP1L was further verified as the downstream target of miR-300. miR-300 mimics blocked LINC01569 upregulation-mediated elevation of FILIP1L. Importantly, the anti-tumor effects mediated by LINC01569 overexpression were abolished by miR-300 mimics and further restored by FILIP1L upregulation. CONCLUSIONS: LINC01569 was expressed at a low level in TNBC and could sponge miR-300 to promote FILIP1L expression, reducing the proliferation and metastasis capability of TNBC. Thus, LINC01569 might be a useful biomarker in the diagnosis and prognosis of metastatic TNBC. Show more

Keywords: Triple-negative breast cancer, LINC01569, miR-300, filamin A-interacting protein 1-like, metastasis

DOI: 10.3233/CBM-230261

Citation: Cancer Biomarkers, vol. 39, no. 2, pp. 79-94, 2024

Authors: Hammad, Gehan | Mamdouh, Samah | Seoudi, Dina Mohamed | Seleem, Mohamed Ismail | Safwat, Gehan | Mohamed, Rania Hassan

Article Type: Research Article

Abstract: BACKGROUND: P-Element-induced wimpy testis (PIWI) proteins, when in combination with PIWI-interacting RNA (piRNA), are engaged in the epigenetic regulation of gene expression in germline cells. Different types of tumour cells have been found to exhibit abnormal expression of piRNA, PIWIL-mRNAs, and proteins. We aimed to determine the mRNA expression profiles of PIWIL1, PIWIL2, PIWIL3, & PIWIL4, in hepatocellular carcinoma patients, and to associate their expression patterns with clinicopathological features. METHODS: The expression patterns of PIWIL1, PIWIL2, PIWIL3, PIWIL4 mRNA, was assessed via real-time quantitative polymerase chain reaction (RT-QPCR), on tissue and serum samples from HCC patients, …their impact for diagnosis was evaluated by ROC curves, prognostic utility was determined, and In Silico analysis was conducted for predicted variant detection, association with HCC microRNAs and Network Analysis. RESULTS: Expression levels were significantly higher in both HCC tissue and serum samples than in their respective controls (p < 0.001). Additionally, the diagnostic performance was assessed, Risk determination was found to be statistically significant. CONCLUSION: PIWIL mRNAs are overexpressed in HCC tissue and serum samples, the expression patterns could be valuable molecular markers for HCC, due to their association with age, tumour grade and pattern. To the best of our knowledge, our study is the first to report the expression levels of all PIWIL mRNA and to suggest their remarkable values as diagnostic and prognostic biomarkers, in addition to their correlation to HCC development. Additionally, a therapeutic opportunity might be also suggested through in silico miRNA prediction for HCC and PIWIL genes through DDX4 and miR-124-3p. Show more

Keywords: Hepatocellular Carcinoma (HCC), PIWIL1, PIWIL2, PIWIL3, PIWIL4, RT-QPCR, relative expression patterns, diagnosis, prognosis

DOI: 10.3233/CBM-230134

Citation: Cancer Biomarkers, vol. 39, no. 2, pp. 95-111, 2024

Authors: Gouzerh, Flora | Vigo, Gwenaëlle | Dormont, Laurent | Buatois, Bruno | Hervé, Maxime R. | Mancini, Maicol | Maraver, Antonio | Thomas, Frédéric | Ganem, Guila

Article Type: Research Article

Abstract: BACKGROUND: Lung cancer is the primary cause of cancer-induced death. In addition to prevention and improved treatment, it has increasingly been established that early detection is critical to successful remission. OBJECTIVE: The aim of this study was to identify volatile organic compounds (VOCs) in urine that could help diagnose mouse lung cancer at an early stage of its development. METHODS: We analysed the VOC composition of urine in a genetically engineered lung adenocarcinoma mouse model with oncogenic EGFR doxycycline-inducible lung-specific expression. We compared the urinary VOCs of 10 cancerous mice and 10 healthy …mice (controls) before and after doxycycline induction, every two weeks for 12 weeks, until full-blown carcinomas appeared. We used SPME fibres and gas chromatography – mass spectrometry to detect variations in cancer-related urinary VOCs over time. RESULTS: This study allowed us to identify eight diagnostic biomarkers that help discriminate early stages of cancer tumour development (i.e., before MRI imaging techniques could identify it). CONCLUSION: The analysis of mice urinary VOCs have shown that cancer can induce changes in odour profiles at an early stage of cancer development, opening a promising avenue for early diagnosis of lung cancer in other models. Show more

Keywords: Lung cancer, early detection, biomarkers, urine, volatile organic compounds, EGFR oncogenic mutation, Mus musculus

DOI: 10.3233/CBM-230070

Citation: Cancer Biomarkers, vol. 39, no. 2, pp. 113-125, 2024

Authors: Zhang, Weidan | Chen, Qiaoqiao | Cheng, Yali | Wang, Miao | Tong, Jinfei | Tang, Rongrong | Pan, Yihong | Yang, Jianhua

Article Type: Research Article

Abstract: PURPOSE: It is widely accepted that there is a strong relationship between iron levels and cancer. This study aimed to investigate the relationship between serum ferritin levels and the severity and prognosis of gynecological malignant tumors. METHODS: This retrospective study included patients with gynecological malignant tumors at Sir Run Run Shaw Hospital in the Department of Obstetrics and Gynecology from January 2013 to June 2019. Patients were grouped according to their serum ferritin level: low (< 13 μ g/L), normal (13–150 μ g/L), and high (> 150 μ …g/L). Correlation analyses were performed between serum ferritin level and other factors. Cox univariable and multivariable analysis and Kaplan-Meier survival curves were used to assess the impact of ferritin on survival in patients with gynecologic tumors. RESULTS: The 402 total patients were divided into a low (n = 37), normal (n = 182), and high (n = 183) ferritin level group. Correlation analyses were performed that WBC, MCV, CRP, CA125, and CA153 were significantly positively correlated with serum ferritin level. The Kaplan-Meier survival curves revealed that of the three groups analyzed, the high serum ferritin level group had a significantly shorter survival time versus the normal and low serum ferritin level groups (log-rank P = 0.003). Univariable Cox regression analysis identified that patients with high serum ferritin levels had a significant correlation with risk of death compared to the patients with lower and normal serum ferritin levels. Serum ferritin was not found to be significant (HR = 0.792, 95% CI: 0.351–1.787, P = 0.574) in the multivariable Cox analysis. CONCLUSION: Although this study did not find serum ferritin to be a significant independent prognosis indicator in gynecological malignant tumors, this study did identify that gynecological malignant tumor patients with high serum ferritin levels have significantly less survival time than patients with low or normal serum ferritin levels. Show more

Keywords: Ferritin, gynecological cancer, clinical parameters, prognosis, biomarkers

DOI: 10.3233/CBM-230040

Citation: Cancer Biomarkers, vol. 39, no. 2, pp. 127-136, 2024

Authors: Setiawan, Lyana | Setiabudy, Rahajuningsih | Kresno, Siti Boedina | Sutandyo, Noorwati | Syahruddin, Elisna | Jovianti, Frederica | Nadliroh, Siti | Mubarika, Sofia | Setiabudy, Rianto | Siregar, Nurjati C.

Article Type: Research Article

Abstract: BACKGROUND: Despite advances in lung cancer treatment, most lung cancers are diagnosed at an advanced stage. Expression of microRNA10b (miR-10b) and fibrinolytic activity, as reflected by soluble urokinase-type plasminogen activator receptor (suPAR) and plasminogen activator inhibitor 1 (PAI-1), are promising biomarker candidates. OBJECTIVE: To assess the expression of miR-10b, and serum levels of suPAR and PAI-1 in advanced stage non-small cell lung cancer (NSCLC) patients, and their correlation with progression, treatment response and prognosis. METHODS: The present prospective cohort and survival study was conducted at Dharmais National Cancer Hospital and included advanced stage …NSCLC patients diagnosed between March 2015 and September 2016. Expression of miR-10b was quantified using qRT-PCR. Levels of suPAR and PAI-1 were assayed using ELISA. Treatment response was evaluated using the RECIST 1.1 criteria. Patients were followed up until death or at least 1 year after treatment. RESULTS: Among the 40 patients enrolled, 25 completed at least four cycles of chemotherapy and 15 patients died during treatment. Absolute miR-10b expression ⩾ 592,145 copies/μ L or miR-10b fold change ⩾ 0.066 were protective for progressive disease and poor treatment response, whereas suPAR levels ⩾ 4,237 pg/mL was a risk factor for progressive disease and poor response. PAI-1 levels > 4.6 ng/mL was a protective factor for poor response. Multivariate analysis revealed suPAR as an independent risk factor for progression (ORadj , 13.265; 95% confidence intervals (CI), 2.26577.701; P = 0.006) and poor response (ORadj , 15.609; 95% CI, 2.221–109.704; P = 0.006), whereas PAI-1 was an independent protective factor of poor response (ORadj , 0.127; 95% CI, 0.019–0.843; P = 0.033). CONCLUSIONS: Since miR-10b cannot be used as an independent risk factor for NSCLC progression and treatment response, we developed a model to predict progression using suPAR levels and treatment response using suPAR and PAI-1 levels. Further studies are needed to validate this model. Show more

Keywords: miR-10b, plasminogen activator inhibitor 1 (PAI-1), soluble urokinase-type plasminogen activator receptor (suPAR), non-small cell lung cancer

DOI: 10.3233/CBM-220222

Citation: Cancer Biomarkers, vol. 39, no. 2, pp. 137-153, 2024