Cancer Biomarkers - Volume 31, issue 1

Authors: Zheng, Xiao-Ying | Cao, Ming-Zheng | Ba, Ying | Li, Yue-Feng | Ye, Jun-Ling

Article Type: Research Article

Abstract: BACKGROUND: Long non-coding RNA testis-specific transcript, Y-linked 15 (TTTY15) is oncogenic in prostate cancer, however its expression and function in colorectal cancer remain largely unknown. METHODS: Paired colorectal cancer samples/normal tissues were collected, and the expression levels of TTTY15, miR-29a-3p and disheveled segment polarity protein 3 (DVL3) were examined by quantitative real-time polymerase chain reaction (qRT-PCR); TTTY15 shRNA and overexpression plasmids were transfected into HT29 and HCT-116 cell lines using lipofectamine reagent, respectively; the proliferation and colony formation were detected by CCK-8 assay and plate colony formation assay; qRT-PCR and Western blot were used to analyze …the changes of miR-29a-3p and DVL3; dual-luciferase reporter gene assay was used to determine the regulatory relationships between miR-29a-3p and TTTY15, miR-29a-3p and DVL3. RESULTS: TTTY15 was significantly up-regulated in cancerous tissues of colorectal cancer samples, positively correlated with the expression of DVL3, while negatively correlated with the expression of miR-29a-3p. After TTTY15 shRNAs were transfected into colorectal cancer cells, the proliferation and metastasis of cancer cells were significantly inhibited, while TTTY15 overexpression had opposite biological effects. TTTY15 shRNA could reduce the expression of DVL3 on both mRNA and protein levels, and the luciferase activity of TTTY15 sequence was also inhibited by miR-29a-3p. DVL3 was also validated as a target gene of miR-29a-3p, and it could be repressed by miR-29a-3p mimics or TTTY15 shRNA. CONCLUSION: TTTY15 is abnormally upregulated in colorectal cancer tissues, and it can modulate the proliferation and metastasis of colorectal cancer cells. It functions as the ceRNA to regulate the expression of DVL3 by sponging miR-29a-3p. Show more

Keywords: LncRNA TTTY15, miR-29a-3p, DVL3, Colorectal cancer

DOI: 10.3233/CBM-201709

Citation: Cancer Biomarkers, vol. 31, no. 1, pp. 1-11, 2021

Authors: El-kott, Attalla F. | ElBealy, Eman R. | Alshehri, Ali S. | El-Kenawy, Ayman E. | Khalifa, Heba S. | AlRamlawy, Amira M.

Article Type: Research Article

Abstract: BACKGROUND: Protein kinase R (PKR) can suppress various types of solid tumors by inducing cellular oxidative stress and apoptosis. Likewise, Slaidorside, a plant flavonoid, was shown to have anti-tumorigenesis in many solid tumors. OBJECTIVE: This study evaluated anti-tumorigenesis of Salidroside in HT29 colorectal cancer and investigated if the underlying mechanism involves activation of PKR. METHODS: Control or PKR deficient cells were cultured in DMEM media treated with 100 μ M Salidroside and cell survival, apoptosis, and other biochemical-related markers were evaluated. RESULTS: Salidroside significantly reduced cell survival and proliferation …and increased the release of lactate dehydrogenase (LDH) and levels of single-stranded DNA (ssDNA). It also increased the protein levels of caspases 3 and 8. Concomitantly, Salidroside increased the protein level and activity of PKR and increased the expression of its downstream targets, p-eIF2α (Ser 51 ), p53 MAPK, and p53. On the contrary, it inhibited the nuclear activation of STAT-3 and NF-κ B p65. In PKR deficient cells, the partial effects of Salidroside on cell survival, proliferation, and apoptotic markers were observed coincided with no effects on the expression of eIF-2α , and JNK, p53, p38 MAPK, and caspase 8 but with a significant decrease in the nuclear activities of STAT3 and NF-κ B. CONCLUSION: Salidroside suppresses the tumorigenesis of HT29 CRC by increasing activation of eIF-2α and JNK and upregulation of p53, p38 MAPK, and caspase-8 through upregulating and activation of PKR. However, the tumor suppressor effect of Salidroside requires also inhibition of STAT3 and NF-κ B in a PKR-independent mechanism. Show more

Keywords: Salidroside, colorectal, HT29, protein kinase R, STAT3, eIF-2α, NF-κB

DOI: 10.3233/CBM-203257

Citation: Cancer Biomarkers, vol. 31, no. 1, pp. 13-25, 2021

Authors: Wang, Pengli | Zheng, Dan | Qi, Hongyang | Gao, Qi

Article Type: Research Article

Abstract: BACKGROUND: MicroRNAs (miRNAs) play potential role in the development of various types of cancer conditions including pancreatic cancer (PC) targeting several cellular processes. Present study was aimed to evaluate function of miR-125b and the mechanism involved in PC. METHODS: Cell migration, MTT and BrdU study was done to establish the migration capability, cell viability and cell proliferation respectively. Binding sites for miR-125b were recognized by luciferase assay, expression of protein by western blot and immunofluorescence assay. In vivo study was done by BALB/c nude xenograft mice for evaluating the function of miR-125b. RESULTS: …The study showed that expression of miR-125b was elevated in PC cells and tissues, and was correlated to proliferation and migration of cells. Also, over-expression of miR-125b encouraged migration, metastasis and proliferation of BxPC-3 cells, the suppression reversed it. We also noticed that thioredoxin-interacting protein (TXNIP) was the potential target of miR-125b. The outcomes also suggested that miR-125b governed the expression of TXNIP inversely via directly attaching to the 3 ′ -UTR activating hypoxia-inducible factor 1α (HIF1α ). Looking into the relation between HIF1α and TXNIP, we discovered that TXNIP caused the degradation and export of HIF1α by making a complex with it. CONCLUSION: The miR-125b-TXNIP-HIF1α pathway may serve useful strategy for diagnosing and treating PC. Show more

Keywords: Pancreatic cancer, miR-125b, HIF1α, TXNIP

DOI: 10.3233/CBM-203112

Citation: Cancer Biomarkers, vol. 31, no. 1, pp. 27-38, 2021

Authors: Xia, Haifeng | Hu, Fang | Pan, Liangbin | Xu, Chengcheng | Huang, Haitao | Chen, Shaomu | Ma, Haitao

Article Type: Research Article

Abstract: This article has been retracted, and the online PDF replaced with this retraction notice. DOI: 10.3233/CBM-229004

Keywords: FAM196B, esophageal cancer, shRNA, proliferation, migration, EMT

DOI: 10.3233/CBM-203023

Citation: Cancer Biomarkers, vol. 31, no. 1, pp. 39-46, 2021

Authors: Shehata, Miral Magdy | Sallam, Al-Aliaa Mohamed | Naguib, Mary Gamal | EL-Mesallamy, Hala Osman

Article Type: Research Article

Abstract: BACKGROUND: Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) and mothers against decapentaplegic homolog 7 (SMAD7) are important transforming growth factor-β (TGF-β ) signaling antagonists, however their roles in acute myeloid leukemia (AML) remains unclear. Telomerase reverse transcriptase (TERT) may be involved in regulating BAMBI and SMAD7 expressions; a role beyond telomeres that is not clinically validated yet. OBJECTIVE: In this study, we examined the expression levels and prognostic values of BAMBI, SMAD7 and TERT and their association with AML patients’ outcomes. METHODS: Blood samples were collected from …74 de-novo AML patients and 16 controls. Real-time quantitative PCR (qRT-PCR) was performed to analyze BAMBI, SMAD7 and TERT expressions. RESULTS: BAMBI and SMAD7 expression in AML were significantly upregulated versus controls (p < 0.05). BAMBI, SMAD7 and TERT levels were significantly correlated together (p < 0.001). Kaplan-Meier analysis indicated that patients with high BAMBI, SMAD7 and TERT expression levels had markedly shorter event free survival (EFS) and overall survival (OS) time (p < 0.01). Furthermore, multivariate analysis revealed that only high BAMBI expression was an independent risk factor for OS (p = 0.001). CONCLUSIONS: BAMBI is a novel biomarker in predicting prognosis in AML patients. Moreover, a potential interplay is found between BAMBI, SMAD7 and TERT in AML pathogenies. Show more

Keywords: Acute myeloid leukemia, transforming growth factor-β, BAMBI, SMAD7, TERT

DOI: 10.3233/CBM-200927

Citation: Cancer Biomarkers, vol. 31, no. 1, pp. 47-58, 2021

Authors: Zhao, Qiaoyun | Xie, Jun | Xie, Jinliang | Zhao, Rulin | Song, Conghua | Wang, Huan | Rong, Jianfang | Yan, Lili | Song, Yanping | Wang, Fangfei | Xie, Yong

Article Type: Research Article

Abstract: BACKGROUND: Gastric cancer (GC) is one of the most deadliest tumours worldwide, and its prognosis remains poor. OBJECTIVE: This study aims to identify and validate hub genes associated with the progression and prognosis of GC by constructing a weighted correlation network. METHODS: The gene co-expression network was constructed by the WGCNA package based on GC samples and clinical data from the TCGA database. The module of interest that was highly related to clinical traits, including stage, grade and overall survival (OS), was identified. GO and KEGG pathway enrichment analyses were performed using the …clusterprofiler package in R. Cytoscape software was used to identify the 10 hub genes. Differential expression and survival analyses were performed on GEPIA web resources and verified by four GEO datasets and our clinical gastric specimens. The receiver operating characteristic (ROC) curves of hub genes were plotted using the pROC package in R. The potential pathogenic mechanisms of hub genes were analysed using gene set enrichment analysis (GSEA) software. RESULTS: A total of ten modules were detected, and the magenta module was identified as highly related to OS, stage and grade. Enrichment analysis of magenta module indicated that ECM-receptor interaction, focal adhesion, PI3K-Akt pathway, proteoglycans in cancer were significantly enriched. The PPI network identified ten hub genes, namely COL1A1 , COL1A2 , FN1 , POSTN , THBS2 , COL11A1 , SPP1 , MMP13 , COMP , and SERPINE1 . Three hub genes (FN1, COL1A1 and SERPINE1 ) were finally identified to be associated with carcinogenicity and poor prognosis of GC, and all were independent risk factors for GC. The area under the curve (AUC) values of FN1, COL1A1 and SERPINE1 for the prediction of GC were 0.702, 0.917 and 0.812, respectively. GSEA showed that three hub genes share 15 common upregulated biological pathways, including hypoxia, epithelial mesenchymal transition, angiogenesis, and apoptosis. CONCLUSION: We identified FN1 , COL1A1 and SERPINE1 as being associated with the progression and poor prognosis of GC. Show more

Keywords: WGCNA, gastric cancer, progression, prognosis, hub genes, prediction, diagnosis

DOI: 10.3233/CBM-200594

Citation: Cancer Biomarkers, vol. 31, no. 1, pp. 59-75, 2021

Authors: Zhu, Pei | Qian, Tingting | Si, Chaozeng | Liu, Yan | Cui, Longzhen | Huang, Wenhui | Fu, Lin | Deng, Cong | Zeng, Tiansheng

Article Type: Research Article

Abstract: BACKGROUND: CPNEs are significant biomarkers which can affect the progression and prognosis of various tumor diseases. However, the prognosis role of CPNEs in multiple myeloma (MM) is still unclear. OBJECTIVES: To investigate the prognosis role of CPNEs in MM. METHODS: Seven hundred and thirty-five samples from two independent data sets were involved to analyze the clinical and molecular characteristics, and prognosis role of the expression of CPNE1-9 in MM. RESULTS: MM patients with higher expressions of CPNE5 and CPNE9 had longer event-free survival (EFS) and …overall survival (OS) compared with CPNE5 low and CPNE9 low expression groups (EFS: P = 0.0054, 0.0065; OS: P = 0.015, 0.016, respectively). Multivariate regression analysis showed that CPNE5 was an independent favorable predictor for EFS and OS (EFS: P = 0.005; OS: P = 0.006), and CPNE9 was an independent positive indicator for EFS (P = 0.002). Moreover, the survival probability and the cumulative event of EFS and OS in CPNE5 high CPNE9 high group were significantly longer than other groups. CONCLUSIONS: High expressions of CPNE5 and CPNE9 might be used as positive indicators for MM, and their combination was a better predictor for the survival of MM patients. Show more

Keywords: Multiple myeloma, CPNE5, CPNE9, prognosis

DOI: 10.3233/CBM-203108

Citation: Cancer Biomarkers, vol. 31, no. 1, pp. 77-85, 2021

Authors: Yan, Yunkun | Mao, Xingning | Zhang, Qingyun | Ye, Yu | Dai, Yan | Bao, Mengying | Zeng, Yanyu | Huang, Rong | Mo, Zengnan

Article Type: Research Article

Abstract: BACKGROUND: The molecular mechanisms involved in the prostate cancer and their relationship with immune cell infiltration are not fully understood. The prostate cancer patients undergoing standard androgen deprivation therapy eventually develop castration resistant prostate cancer (CRPC) for which there is no effective treatment currently available, and the hub genes involved in this process remain unclear. OBJECTIVE: To study prostate cancer systematically and comprehensively. METHODS: Differentially expressed genes (DEGs) of prostate cancer were screened in The Cancer Genome Atlas (TCGA) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were …performed. Connectivity Map (Cmap) software was applied to discover potential treatment drugs. A protein-protein interaction (PPI) analysis was performed to obtained the hub genes, and the relationship between hub genes and immune cell infiltration was investigated. Next, RNAseq data of hormone-sensitive prostate cancer samples and CRPC samples obtained from TCGA database was further analyzed to identify DEGs. Finally, a PPI analysis was performed to obtain the hub genes. RESULTS: A total of 319 DEGs were identified between prostate cancer samples and normal adjacent samples from TCGA database using comparative analysis. The KEGG pathway analysis showed significant correlations with drug metabolism, metabolism of xenobiotics by cytochrome P450, and chemical carcinogenesis. AMACR , FOLH1 and NPY, three hub genes, were found to be upregulated. FOLH1 was positively correlated with CD8 + T cell infiltration. FOLH1 , AMACR, and NPY were negatively correlated with CD4 + T cell infiltration. A total of 426 DEGs were identified from RNAseq data of hormone-sensitive prostate cancer samples and CRPC samples using further comparative analysis. KEGG pathway enrichment analysis showed significant correlations with arachidonic acid metabolism, PPAR signaling pathway, AMPK signaling pathway, and metabolic pathways. The top 10 hub genes in PPI network were screened out, including PPARG , SREBF1 , SCD , HMGCR , FASN , PTGS2 , HMGCS2 , SREBF2 , FDFT1, and INSIG1 . Among them, SCD and FASN are expected to be the potential therapeutic targets for CRPC. CONCLUSIONS: AMACR , FOLH1 and NPY may be effective therapeutic targets and specific diagnostic markers for prostate cancer. AMACR , FOLH1, and NPY are also closely associated with immune cell infiltration in prostate cancer. Moreover, aminoglutethimide and resveratrol were found to be the promising drugs for treating prostate cancer. The progression of hormone-sensitive prostate cancer to CRPC may be related to arachidonic acid metabolism, PPAR signaling pathway, AMPK signaling pathway, and other metabolic pathways. SCD and FASN are expected to be the potential therapeutic targets for CRPC. Show more

Keywords: TCGA, castration resistant prostate cancer, Cmap, immune cell infiltration

DOI: 10.3233/CBM-200939

Citation: Cancer Biomarkers, vol. 31, no. 1, pp. 87-96, 2021

Article Type: Correction

DOI: 10.3233/CBM-219050

Citation: Cancer Biomarkers, vol. 31, no. 1, pp. 97-, 2021