Cancer Biomarkers - Volume 40, issue 3-4

Authors: Zhu, Wenjing | Song, Shu | Xu, Yangchun | Sheng, Hanyue | Wang, Shuang

Article Type: Research Article

Abstract: Epithelial membrane protein 3 (EMP3) belongs to the peripheral myelin protein 22 kDa (PMP22) gene family, characterized by four transmembrane domains and widespread expression across various human tissues and organs. Other members of the PMP22 family, including EMP1, EMP2, and PMP22, have been linked to various cancers, such as glioblastoma, laryngeal cancer, nasopharyngeal cancer, gastric cancer, breast cancer, and endometrial cancer. However, few studies report on the function and relevance of EMP3 in tumorigenicity. Given the significant structural similarities among members of the PMP22 family, there are likely potential functional similarities as well. Previous studies have established the regulatory role …of EMP3 in immune cells like T cells and macrophages. Additionally, EMP3 is found to be involved in critical signaling pathways, including HER-2/PI3K/Akt, MAPK/ERK, and TGF-beta/Smad. Furthermore, EMP3 is associated with cell cycle regulation, cellular proliferation, and apoptosis. Hence, it is likely that EMP3 participates in cancer development through these aforementioned pathways and mechanisms. This review aims to systematically examine and summarize the structure and function of EMP3 and its association to various cancers. EMP3 is expected to emerge as a significant biological marker for tumor prognosis and a potential target in cancer therapeutics. Show more

Keywords: Epithelial membrane protein 3, cancer, transmembrane protein, signaling pathway, glioma

DOI: 10.3233/CBM-230504

Citation: Cancer Biomarkers, vol. 40, no. 3-4, pp. 227-239, 2024

Authors: Peng, Ruiting | Huang, Yun | Huang, Ping | Liu, Linyi | Cheng, Lei | Peng, Xian

Article Type: Research Article

Abstract: Transforming growth factor-β (TGF-β ) is a multifunctional cytokine that plays a vital role in regulating cell growth, differentiation and survival in various tissues. It participates in a variety of cellular processes, including cell apoptosis, cell migration and evasion, and plays a paradoxical role in tumor genesis and development. In the early stage of tumor, TGF-β inhibits the occurrence of tumor by inhibiting cell proliferation and regulating cell apoptosis. In the advanced stage of tumor, TGF-β promotes tumor development and affects prognosis by promoting cell survival and proliferation, cell …migration and invasion, participates in immune escape, etc. In this article, we will review the paradoxical role of TGF-β on the occurrence and development of oral squamous cell carcinoma. Show more

Keywords: TGF-β, OSCC, signal transduction, cell proliferation, cell apoptosis, cell migration, cell invasion, EMT

DOI: 10.3233/CBM-230354

Citation: Cancer Biomarkers, vol. 40, no. 3-4, pp. 241-250, 2024

Authors: Xu, Rui | Feng, Huayun | Liang, Haojie | Li, Yaoping

Article Type: Research Article

Abstract: Colorectal cancer (CRC) is one of the most common digestive tract malignant tumors, which has a high mortality rate especially for patients with CRC recurrence. However, the pathological mechanism of recurrence of CRC is unclear. In this study, we integrated multiple cohort datasets and databases to clarify and verify potential key candidate biomarkers and signal transduction pathways in recurrence of CRC. As results, 628 DEGs were identified from GSE33113 and GSE2630 datasets and their function and pathway were analyzed. 14 hub genes related to CRC recurrence were screened from and their influence on survival were analyzed. Two key genes (IL1B …and DDAH1) regarded as prognostic factors were further screened. Relapse-free survival results indicated the interaction between IL1B and DDAH1 genes and B cells was the most obvious and correlated with survival, with statistical significance (P < 0.05). Specially, cox regression analysis suggested that patients with T1 and N0 stages had a higher risk of recurrence than patients with T2 and N1. This work would provide potential value for prognosis, and would promote molecular targeting therapy for CRC recurrence. Show more

Keywords: Colorectal cancer, biological information, prognostic analysis, recurrence, immune infiltration

DOI: 10.3233/CBM-230390

Citation: Cancer Biomarkers, vol. 40, no. 3-4, pp. 251-262, 2024

Authors: Ma’touq, Jumana | Alnuman, Nasim

Article Type: Research Article

Abstract: BACKGROUND: Breast cancer (BC) is considered the world’s most prevalent cancer. Early diagnosis of BC enables patients to receive better care and treatment, hence lowering patient mortality rates. Breast lesion identification and classification are challenging even for experienced radiologists due to the complexity of breast tissue and variations in lesion presentations. OBJECTIVE: This work aims to investigate appropriate features and classification techniques for accurate breast cancer detection in 336 Biglycan biomarker images. METHODS: The Biglycan biomarker images were retrieved from the Mendeley Data website (Repository name: Biglycan breast cancer dataset). Five features were …extracted and compared based on shape characteristics (i.e., Harris Points and Minimum Eigenvalue (MinEigen) Points), frequency domain characteristics (i.e., The Two-dimensional Fourier Transform and the Wavelet Transform), and statistical characteristics (i.e., histogram). Six different commonly used classification algorithms were used; i.e., K-nearest neighbours (k-NN), Naïve Bayes (NB), Pseudo-Linear Discriminate Analysis (pl-DA), Support Vector Machine (SVM), Decision Tree (DT), and Random Forest (RF). RESULTS: The histogram of greyscale images showed the best performance for the k-NN (97.6%), SVM (95.8%), and RF (95.3%) classifiers. Additionally, among the five features, the greyscale histogram feature achieved the best accuracy in all classifiers with a maximum accuracy of 97.6%, while the wavelet feature provided a promising accuracy in most classifiers (up to 94.6%). CONCLUSION: Machine learning demonstrates high accuracy in estimating cancer and such technology can assist doctors in the analysis of routine medical images and biopsy samples to improve early diagnosis and risk stratification. Show more

Keywords: SDG3, breast cancer, feature selection, classification, Biglycan biomarker

DOI: 10.3233/CBM-230544

Citation: Cancer Biomarkers, vol. 40, no. 3-4, pp. 263-273, 2024

Authors: Fishchuk, Liliia | Rossokha, Zoia | Lobanova, Olga | Cheshuk, Valeriy | Vereshchako, Roman | Vershyhora, Viktoriia | Medvedieva, Nataliia | Dubitskaa, Olha | Gorovenko, Natalia

Article Type: Research Article

Abstract: BACKGROUND: The BRCA2 gene is an important tumour suppressor in breast cancer, and alterations in BRCA2 may lead to cancer progression. The aim of the study was to investigate the association of hypermethylation of the BRCA2 gene promoter and its co-hypermethylation with the BRCA1 gene promoter with the development and course of breast cancer in women. METHODS: This study included 74 women with breast cancer (tumour tissue samples and peripheral blood) and 62 women without oncological pathology (peripheral blood) – control group. RESULTS: Hypermethylation of the BRCA2 gene was significantly more …frequently detected in the tumour tissue of women with breast cancer compared to their peripheral blood and peripheral blood of control subjects (p = 0.0006 and p = 0.00001, respectively). Hypermethylation of BRCA2 was more frequently detected in patients with breast cancer over the age of 50 and in patients with higher Ki67 expression levels (p = 0.045 and p = 0.045, respectively). There was a high frequency of unmethylated BRCA1 and BRCA2 gene combination in women of the control group compared to women with breast cancer, both in blood samples and tumour tissue samples (p = 0.014 and p = 0.00001, respectively). CONCLUSION: Our study confirms the hypothesis that BRCA2 hypermethylation plays an important role in the pathogenesis of breast cancer and the importance of assessing its co-hypermethylation with BRCA1 in predicting the course of the disease. Show more

Keywords: Breast cancer, hypermethylation, BRCA2, BRCA1, gene

DOI: 10.3233/CBM-230458

Citation: Cancer Biomarkers, vol. 40, no. 3-4, pp. 275-283, 2024

Authors: Yang, Yi | Zhang, Yi | Feng, Tongbao | Zhu, Chunfu

Article Type: Research Article

Abstract: BACKGROUND: Numerous studies have shown that m6 A plays an important regulatory role in the development of tumors. HNRNPA2B1, one of the m6 A RNA methylation reading proteins, has been proven to be elevated in human cancers. OBJECTIVE: In this study, we aimed to identify the role of HNRNPA2B1 in breast cancer. METHODS: HNRNPA2B1 expression was investigated via RT-qPCR and TCGA database in breast cancer. Then, the function of HNRNPA2B1 on cancer cell was measured by CCK8 assays, colony formation and scratch assays. In addition, HNRNPA2B1 expression in BRCA was explored via the …Wilcoxon signed-rank test, KruskalWallis test and logistic regression. The association with HNRNPA2B1 expression and survival were considered by KaplanMeier and Cox regression analyses. The biological function of HNRNPA2B1 was analyzed via gene set enrichment analysis (GSEA) and the cluster Profiler R software package. RESULTS: We found that HNRNPA2B1 was highly expressed and induced cell proliferation and migration in breast cancer. Moreover, we observed HNRNPA2B1 induced tumor growth in vivo . In addition, we also found HNRNPA2B1 expression was associated with characteristics and prognosis in breast cancer patients. CONCLUSION: Our findings suggested that HNRNPA2B1 promoted tumor growth and could function as a new potential molecular marker in breast cancer. Show more

Keywords: HNRNPA2B1, cell proliferation, molecular marker, breast cancer

DOI: 10.3233/CBM-230576

Citation: Cancer Biomarkers, vol. 40, no. 3-4, pp. 285-296, 2024

Authors: Zhong, Wang-Jing | Zhang, Li-Zhen | Yue, Feng | Yuan, Lezhong | Zhang, Qikeng | Li, Xuesong | Lin, Li

Article Type: Research Article

Abstract: BACKGROUND: WEE1 is a critical kinase in the DNA damage response pathway and has been shown to be effective in treating serous uterine cancer. However, its role in gliomas, specifically low-grade glioma (LGG), remains unclear. The impact of DNA methylation on WEE1 expression and its correlation with the immune landscape in gliomas also need further investigation. METHODS: This study used data from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene Expression Omnibus (GEO) and utilized various bioinformatics tools to analyze gene expression, survival, gene correlation, immune score, immune infiltration, genomic alterations, tumor …mutation burden, microsatellite instability, clinical characteristics of glioma patients, WEE1 DNA methylation, prognostic analysis, single-cell gene expression distribution in glioma tissue samples, and immunotherapy response prediction based on WEE1 expression. RESULTS: WEE1 was upregulated in LGG and glioblastoma (GBM), but it had a more significant prognostic impact in LGG compared to other cancers. High WEE1 expression was associated with poorer prognosis in LGG, particularly when combined with wild-type IDH. The WEE1 inhibitor MK-1775 effectively inhibited the proliferation and migration of LGG cell lines, which were more sensitive to WEE1 inhibition. DNA methylation negatively regulated WEE1, and high DNA hypermethylation of WEE1 was associated with better prognosis in LGG than in GBM. Combining WEE1 inhibition and DNA methyltransferase inhibition showed a synergistic effect. Additionally, downregulation of WEE1 had favorable predictive value in immunotherapy response. Co-expression network analysis identified key genes involved in WEE1-mediated regulation of immune landscape, differentiation, and metastasis in LGG. CONCLUSION: Our study shows that WEE1 is a promising indicator for targeted therapy and prognosis evaluation. Notably, significant differences were observed in the role of WEE1 between LGG and GBM. Further investigation into WEE1 inhibition, either in combination with DNA methyltransferase inhibition or immunotherapy, is warranted in the context of LGG. Show more

Keywords: WEE1, DNA methylation, prognosis, immunotherapy, low-grade glioma

DOI: 10.3233/CBM-230517

Citation: Cancer Biomarkers, vol. 40, no. 3-4, pp. 297-317, 2024

Authors: Ji, Lanting | Liang, Shuang | Cheng, Yahsin | Gao, Ruifang | Yan, Wenpeng | Pang, Fang | Zhang, Fang

Article Type: Research Article

Abstract: BACKGROUND: Necroptosis is a caspase-independent regulated necrotic cell death modality that elicits strong adaptive immune responses, and has the potential to activate antitumor immunity. Long non-coding RNAs (lncRNAs) have critical effects on oral squamous cell carcinoma (OSCC), which are closely associated with the prognosis and immune regulation of OSCC patients. OBJECTIVE: This study aimed to identify a novel necroptosis-related lncRNAs signature to predict the prognosis and immune response of OSCC patients and provide patients with anti-tumor drug selection through bioinformatics analysis and in vitro experiments. METHODS: A series of analyses, including differential lncRNA …screening, survival analysis, Cox regression analysis, ROC analysis, nomogram prediction, enrichment analysis, tumor-infiltrating immune cells, drug sensitivity analysis, and consensus cluster analysis, were performed to determine and validate the prognostic value of necroptosis-associated lncRNAs signature in OSCC. And real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression levels of these lncRNAs. RESULTS: This signature including 5 lncRNAs (AC099850.3, StarD4-AS1, AC011978.1, LINC01503, CDKN2A-DT) in OSCC associated with necroptosis were established and verified by bioinformatics. Further, ROC, K-M, univariate/multivariate Cox regression, and nomogram analysis were used to evaluate the model’s features for OSCC prognosis. Using multiple bioinformatics techniques, the levels of tumor-infiltrating immune cells, immune checkpoints and semi-inhibitory concentrations showed significant differences across risk subtypes. By consensus cluster analysis, there were significant differences between clusters in survival, immune checkpoint expression, clinicopathological correlation, and tumor immunity. RT-qPCR showed that AC099850.3, AC011978.1, LINC01503 were up-regulated, STARD4-AS1 and CDKN2A-DT were down-regulated in OSCC cell lines compared with human normal oral keratinoid cell line. CONCLUSION: We established 5-NRLs markers, which is useful for assessing OSCC immune response and prognosis, recommending personalized antitumor drugs. The expression level of 5-NRLs in OSCC was identified in vitro, and the results preliminarily verified this model. And this study would generate new insights for future experimental research. Show more

Keywords: Oral squamous cell carninoma, risk model, prognosis, lncRNAs, biomarkers

DOI: 10.3233/CBM-230407

Citation: Cancer Biomarkers, vol. 40, no. 3-4, pp. 319-342, 2024