Cancer Biomarkers - Volume Pre-press, issue Pre-press

Authors: Ling, Qing | Mao, Shihui | Pan, Jiajia | Wei, Wenwen | Qian, Yu | Li, Fenglin | Huang, Shujuan | Ye, Wenle | Lin, Xiangjie | Huang, Jiansong | Wang, Jinghan | Jin, Jie

Article Type: Research Article

Abstract: BACKGROUND: Fatty acid oxidation has been considered as an important energy source for tumorigenesis and development. Several studies have investigated the role of CPT1A, a kind of fatty acid oxidation rate-limiting enzyme, in AML. However, prognostic value and regulatory network of another subtype, CPT1B in AML remains elusive. This study aims to clarify the independent prognostic role of CPT1B in CN-AML based on clinical data and molecular level data (mRNA, miRNA and lncRNA). OBJECTIVE: The aim of this study is to investigate the prognostic value of CPT1B in AML patients. METHODS: First, we …analyzed the CPT1B expression in AML cohort via the online database “GEPIA”. Subsequently, miRNA-mRNA and ceRNA networks were constructed to help predict the role of CPT1B in AML. Several molecules which showed the prognostic value and metabolic function of CPT1B were identified. Finally, the expression of CPT1B in our own cohort of 324 CN-AML patients was analyzed to clarify the results. RESULTS: It was found that CPT1B was markedly higher in AML patients compared to normal people and this upregulation was associated with the poor clinical outcome. Several molecules revealed the possible regulatory mechanism of CPT1B in AML. CONCLUSION: CPT1B is a potential prognostic factor and a therapeutic target for AML treatment. Show more

Keywords: CPT1B, prognostic factor, differrential molecules, miRNA-mRNA network, ceRNA network

DOI: 10.3233/CBM-210043

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-13, 2023

Authors: Thokerunga, Erick | 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. Pre-press, no. Pre-press, pp. 1-12, 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. Pre-press, no. Pre-press, pp. 1-10, 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. Pre-press, no. Pre-press, pp. 1-11, 2023

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. Pre-press, no. Pre-press, pp. 1-18, 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. Pre-press, no. Pre-press, pp. 1-13, 2023

Authors: Pecqueux, Mathieu | Wende, Beate | Sommer, Ulrich | Baenke, Franziska | Oehme, Florian | Hempel, Sebastian | Aust, Daniela | Distler, Marius | Weitz, Jürgen | Kahlert, Christoph

Article Type: Research Article

Abstract: BACKGROUND: Pancreatic cancer is the 4th leading cause of cancer-related death with poor survival even after curative resection. RAB27A and RAB27B are key players in the exosome pathway where they play important roles in exosome secretion. Evidence suggests that RAB27A and RAB27B expression not only leads to tumor proliferation and invasion, but also plays an important role in antigen transfer necessary for anticancer immunity. OBJECTIVE: In this study, we analyze the expression of RAB27A and RAB27B in patients after pancreatic cancer surgery with or without adjuvant chemotherapy and its influence on overall survival. METHODS: …We analyzed a total of 167 patients with pancreatic cancer for their RAB27A and RAB27B expression. We dichotomized the patients along the median and compared survival in patients with high and low RAB27A and RAB27B expression with or without adjuvant chemotherapy treatment. RESULTS: We found a significant improvement in overall survival in patients with a negative resection margin (p = 0.037) and in patients who received adjuvant chemotherapy (p = 0.039). The survival benefit after chemotherapy was dependent on RAB27B expression status: only the subgroup of patients with high RAB27B expression benefited from adjuvant chemotherapy (p = 0.006), but not the subgroup with low RAB27B expression (p = 0.59). Patients with high RAB27B expression who did not receive adjuvant chemotherapy showed a trend towards worse survival compared to the other subgroups. This difference was abolished after treatment with adjuvant chemotherapy. CONCLUSION: These results suggest that RAB27B expression in pancreatic cancer might identify a subgroup of patients with poor survival who might respond well to adjuvant chemotherapy. If resectable, these patients could be considered for neoadjuvant chemotherapy to minimize the risk of not receiving adjuvant chemotherapy. Further prospective studies are needed to confirm these findings. Show more

Keywords: Exosomes, RAB27B, pancreatic cancer, chemotherapy, treatment response

DOI: 10.3233/CBM-220460

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-9, 2023

Authors: Mosaad, Hala | Ahmed, Mona Mostafa | Elaidy, Mostafa M. | Elfarargy, Ola M. | Abdelwahab, Mai Mohamed | Abdelnour, Hanim M.

Article Type: Research Article

Abstract: BACKGROUND: Colorectal cancer (CRC) is the most common malignant tumor of the gastrointestinal tract with unfavorable prognosis. Therefore, novel biomarkers that may be used for new diagnostic strategies and drug-targeting therapy should be developed. OBJECTIVES: To investigate the expression of miR-29b in CRC and its association with ETV4 and cyclin D1 expression. Moreover, the current work aims to investigate the association between them and the clinicopathological features of CRC. METHODS: The expression of miR-29b and ETV4 (by qRT-PCR) and ETV4 and cyclin D1 (immunohistochemistry) was investigated in 65 cases of colon cancer and …surrounding healthy tissues. RESULTS: MiR-29b down-regulated and ETV4 and Cyclin D1 up-regulated significantly in colon cancer tissues compared to normal nearby colonic tissues. In addition, significant associations between ETV4 and cyclin D1 expressions and progressive stage and lymph node (LN) metastasis (P < 0.001 for each) were found. Furthermore, there was a negative correlation between miR-29b gene expression and ETV4 gene expression (r = - 0.298, P < 0.016). CONCLUSION: Down-regulation of miR-29b and over-expression of ETV4 and cyclin D1 may be utilized as early diagnostic marker for development of colon cancer. ETV4 and cyclin D1 correlate with poor prognostic indicators and considered as a possible target for therapy in colon cancer. Show more

Keywords: Colon cancer, miR-29b, ETV4, cyclin D1

DOI: 10.3233/CBM-220349

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-11, 2023

Authors: He, Jiarong | Zhou, Wen | Zhang, Mingming

Article Type: Research Article

Abstract: BACKGROUND: Pyroptosis could regulate tumor cell trafficking, invasion, and metastasis, as well as the tumor microenvironment (TME). However, prognostic characteristics of pyroptosis-related genes (PRGs) and their effect on the progression of glioma remain insufficient. METHODS: The genetic, transcriptional, and survival data of patients with glioma used for bioinformatic analysis were obtained from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. RESULTS: Screening of two different molecular subtypes revealed that PRG variations were associated with characteristics of TME cell infiltration, clinicopathological characteristics, and prognosis of patients with glioma. After …Cox regression of differentially expressed genes, a risk score for predicting overall survival (OS) and progression-free survival (PFS) were calculated. Its predictive accuracy in patients with glioma was validated. The high-risk group of PRG signature had a poorer OS than the low-risk group (training cohort, P < 0.001; validation cohort, P < 0.001). A high risk score implies more immune cell infiltration and better immunotherapy response to immune checkpoint blockers. In addition, the differential expression of three pyroptosis-pairs in tumor and normal tissues was identified. Furthermore, the risk score was significantly associated with chemotherapeutic drug sensitivity and cancer stem cell (CSC) index. Subsequently, a highly accurate nomogram was established to facilitate applicability in the preliminary clinical application of risk score. CONCLUSION: Our findings may provide the basis for future research targeting pyroptosis in glioma and evaluation of prognosis and development of more effective immunotherapy strategies. Show more

Keywords: Glioma, pyroptosis, mutation burden, signature, tumor microenvironment

DOI: 10.3233/CBM-220362

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-17, 2023

Authors: Yang, Yixing | Zhao, Weizhen | Wang, Yueyuan | Du, Jun

Article Type: Research Article

Abstract: BACKGROUND: Liver hepatocellular carcinoma (LIHC) is one of the most malignancy over the world. Previous studies have proven that Molecules Interacting with CasL-Like 1 (MICALL1) participated in cellular trafficking cascades, while there has no study to explore the function and carcinogenic mechanism MICALL1 in LIHC. METHODS: We aimed to investigate the relationship between MICALL1 mRNA expression and LIHC using TCGA database. The expression of MICALL1 protein in clinic samples were examined by UALCAN database. Kaplan-Meier method was used for survival analysis. Logistic regression and Cox regression were performed to evaluate the prognostic significance of MICALL1. The …MICALL1-binding protein were built by the STRING tool. Enrichment analysis by GO, KEGG and GSEA was used to explore possible function of MICALL1. The ssGSEA method was used to investigate the association between MICALL1 expression and the immune infiltration level in LIHC. RESULTS: The expression and prognostic value of different MICAL family members in LIHC were evaluated. The expression of MICALL1 was significantly increased at both the transcript and protein levels in LIHC tissues. Further, the LIHC patients with high MICALL1 levels showed a worse OS, DSS and PFI. Some clinicopathologic features were identified to be related to MICALL1 expression in LIHC included clinical T stage, pathologic stage, histologic grade and AFP concentration. Univariate and multivariate survival analysis showed that MICALL1 was an independent prognostic marker for OS and DSS. Further enrichment analysis revealed that the K-RAS, TNFα /NF-κ B and inflammatory response were significantly enriched in the high MICALL1 expression group. Immune infiltration analysis showed that high MICALL1 expression was correlated with infiltration level of macrophage cells, Th2 cells and some other immune cell types, including TFH. CONCLUSIONS: MICALL1 expression was significantly associated with immune cell infiltration and may regarded as a promising prognostic biomarker for LIHC patients. Show more

Keywords: MICALL1, overall survival, prognosis, LIHC, immune infiltration

DOI: 10.3233/CBM-220370

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-14, 2023