Cancer Biomarkers - Volume 38, issue 2

Authors: Wang, Chaofeng | Song, Dezhi | Huang, Qian | Liu, Qian

Article Type: Research Article

Abstract: Cancer has become a leading cause of morbidity and mortality in recent years. Its high prevalence has had a severe impact on society. Researchers have achieved fruitful results in the causative factors, pathogenesis, treatment strategies, and cancer prevention. Semaphorin 3F (SEMA3F), a member of the signaling family, was initially reported in the literature to inhibit the growth, invasion, and metastasis of cancer cells in lung cancer. Later studies showed it has cancer-inhibiting effects in malignant tumors such as breast, colorectal, ovarian, oral squamous cell carcinoma, melanoma, and head and neck squamous carcinoma. In contrast, recent studies have reported that SEMA3F …is expressed more in hepatocellular carcinoma than in normal tissue and promotes metastasis of hepatocellular carcinoma. We chose lung, breast, colorectal, and hepatocellular carcinomas with high clinical prevalence to review the roles and molecular mechanisms of SEMA3F in these four carcinomas. We concluded with an outlook on clinical interventions for patients targeting SEMA3F. Show more

Keywords: SEMA3F, cancer, anti-oncogene

DOI: 10.3233/CBM-230085

Citation: Cancer Biomarkers, vol. 38, no. 2, pp. 131-142, 2023

Authors: Su, Zhiyong | Wang, Guanghui | Li, Leilei

Article Type: Research Article

Abstract: BACKGROUND: Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are common male diseases whose incidence rates gradually increase with age. They seriously affect men’s physical health and quality of life. This study aimed to identify new biomarkers for the diagnosis of BPH and PCa. METHODS: Two datasets, GSE28204 and GSE134051 (including human PCa and BPH), were downloaded from the GEO database. The batch effect was removed for merging, and then differential gene expression analysis was conducted to identify BPH and PCa cases. The diagnostic biomarkers of BPH and PCa were further screened using machine learning and …bioinformatics. ROC curves were drawn to evaluate the diagnostic accuracy of the selected biomarkers. An online website and qPCR were used to preliminarily explore the expression levels of PCa biomarkers. The correlations between the expression of biomarkers and the tumor microenvironment, tumor mutation load and immunotherapy drugs were evaluated. RESULTS: We identified fifteen genes (CHRDL1, DES, FLNC, GSTP1, MYL9, TGFB3, NEFH, TAGLN, SPARCL1, SYNM, TRPM8, HPN, PLA2G7, ENTPD5 and GPR160) as critical diagnostic biomarkers. After reviewing the literature on all selected biomarkers, we found few studies on the four genes CHRDL1, NEFH, TAGLN and SYNM in BPH or PCa. We defined these four genes as new potential diagnostic biomarkers (NPDBs) of BPH and PCa. All NPDBs were downregulated in PCa patients and PCa cell lines and upregulated in BPH patients and cell lines. When the immune landscape and mutation frequencies were analyzed, the results showed that the tumor microenvironment (TME), immune landscape, tumor mutation burden, and drug response were significantly correlated with NPDB expressions. CONCLUSIONS: We found four new diagnostic markers of BPH and PCa, which may facilitate the early diagnosis, treatment, and immunotherapeutic responses assessment and may be of major value in guiding clinical practice. Show more

Keywords: Prostate cancer, benign prostatic hyperplasia, lasso regression, SVM-RFE, tumor microenvironment

DOI: 10.3233/CBM-230028

Citation: Cancer Biomarkers, vol. 38, no. 2, pp. 143-159, 2023

Authors: Zhang, Yuliang | Zhou, Anyan | Nian, Jiabin | Liu, Shuzhou | Wei, Xin

Article Type: Research Article

Abstract: BACKGROUND: The study of molecular markers for diagnosis and prognosis is of great clinical significance for HNSCC patients. In this study, we proposed that FSCN1 has a potential indication for prognosis and is essential for the migration of HNSCC. METHODS: We analyzed the expression and survival association of FSCN1 in HNSCC using TCGA data. We compared the expression of FSCN1 in tumors from primary and metastasis HNSCC patients using QPCR, western blotting, and immunochemistry staining. We determined the migration velocity of multiple HNSCC cell lines using a chemotaxis migration assay. We analyzed the correlation between FSCN1 …expression and HNSCC cell migration. We also test the effect of FSCN1 knockdown and overexpression on HNSCC cell migration. RESULTS: FSCN1 was overexpressed in HNSCC than pair normal tissues and metastasis HNSCC than primary HNSCC. FSCN1 expression was associated with significantly poorer overall survival of HNSCC patients. FSCN1 was potentially associated with immune cell infiltration and migration-associated genes. FSCN1 level was correlated with the migration in HNSCC cell lines. Knockdown of FSCN1 reduced the migration and the overexpression of FSCN1 promoted the migration of HNSCC cell lines. CONCLUSION: FSCN1 is a potential prognostic marker and a critical biomolecule for the migration of HNSCC. Show more

Keywords: FSCN1, prognosis, HNSCC, migration

DOI: 10.3233/CBM-220409

Citation: Cancer Biomarkers, vol. 38, no. 2, pp. 161-176, 2023

Authors: Wu, Zhiqiang | Zeng, Xiaofei | Wang, Hong | Wang, Xianbo

Article Type: Research Article

Abstract: BACKGROUND: It has been discovered that lncRNA ARAP1-AS1 is upregulated and operates as a tumor promoter in many cancers. However, its pattern of expression and potential mechanism in lung adenocarcinoma (LUAD) is still unknown. METHODS: The levels of lncRNA ARAP1-AS1, miR-8068, and CEACAM5 expressions in LUAD cell lines and tissues were assessed by conducting western blot and RT-qPCR analyses. MiR-8068’s potential targeting relationships with lncRNA ARAP1-AS1 and CEACAM5 were ascertained by performing bioinformatics analysis. The interaction of lncRNA ARAP1-AS1 with miR-8068 was validated by means of by RIP and luciferase reporter experiments. CCK-8, cell adhesion, and …Transwell migration experiments were conducted to study how lncRNA ARAP1-AS1 affects LUAD cell migration, adhesion, and proliferation. To confirm the function of lncRNA ARAP1-AS1 in vivo , a tumor formation experiment was executed. RESULTS: An elevated expression of lncRNA ARAP1-AS1 was observed among the LUAD cells and tissues. The overexpression of lncRNA ARAP1-AS boosted cell proliferation, adhesion, and migration in LUAD and also favored in vivo tumor growth. MiR-8068 was found to be lncRNA ARAP1-AS1’s target gene. MiR-8068 overexpression partially antagonized lncRNA ARAP1-AS1’s promotive effect on proliferation, viability, and adhesion. Meanwhile CEACAM5 could alleviate the miR-8068-induced inhibition of tumor growth. The negative correlation of miR-8068 with lncRNA ARAP1-AS1 or CEACAM5 was also revealed. CONCLUSION: To upregulate CEACAM5 expression lncRNA ARAP1-AS1 targeted miR-8068, thus promoting the progression of LUAD. This indicates that the lncRNA ARAP1-AS1/miR-8068/CEACAM5 axis has potential as a therapeutic target in LUAD treatment. Show more

Keywords: ARAP1-AS1, miR-8068, CEACAM5, lung adenocarcinoma

DOI: 10.3233/CBM-220223

Citation: Cancer Biomarkers, vol. 38, no. 2, pp. 177-189, 2023

Authors: Wang, Xiuli | Zhao, Baoshan | Ren, Dan | Hu, Xiaolei | Qiao, Juanjuan | Zhang, Dongmei | Zhang, Yanzhi | Pan, Yu | Fan, Yuhua | Liu, Lili | Wang, Xiaoxue | Ma, Huanhuan | Jia, Xueling | Song, Sihang | Zhao, Chong | Liu, Jingbo | Wang, Lin

Article Type: Research Article

Abstract: BACKGROUD: Previous in vitro studies have indicated that pyrimidinergic receptor P2Y 6 (P2RY6 , P2Y 6 receptor) may function as a cancer-promoting factor in lung adenocarcinoma (LUAD). However, the prognostic significance of P2RY6 expression in LUAD has not been investigated. OBJECTIVE: This study aimed to assess the impact of P2RY6 expression on the survival of patients with LUAD. METHODS: First, we assessed P2RY6 mRNA and protein expression in LUAD and non-cancerous lung tissues using the online bioinformatics analysis tool GEPIA, …fresh LUAD tissues, and LUAD tissue microarrays (TMAs). Second, we investigated the correlation between P2RY6 expression and clinicopathological parameters of LUAD patients based on data from The Cancer Genome Atlas (TCGA) database and TMAs. Finally, we analyzed the prognostic significance of P2RY6 expression in LUAD using the online survival analysis tool Kaplan-Meier Plotter and data from TMAs. RESULTS: We demonstrated that P2RY6 mRNA and protein expression levels in LUAD tissues were significantly higher than those in non-cancerous lung tissues. The expression of P2RY6 in LUAD was positively correlated with poor differentiation, more lymph node metastasis, and more advanced clinical stage. Higher P2RY6 expression level was correlated with shorter survival of the LUAD patients. Univariate and multivariate Cox regression analyses indicated that higher P2RY6 tumor expression was an independent unfavorable prognostic factor for LUAD patients. CONCLUSIONS: P2RY6 expression was elevated in LUAD and correlated with poor prognosis. Show more

Keywords: Lung adenocarcinoma, purinergic signaling, pyrimidinergic receptor P2Y6, prognosis

DOI: 10.3233/CBM-230137

Citation: Cancer Biomarkers, vol. 38, no. 2, pp. 191-201, 2023

Authors: Tiwari, Shikha | Pandey, Ritu | Kumar, Vinay | Das, Saikat | Gupta, Vikas | Vishwakarma, Supriya | Nema, Rajeev | Sindhuja, Tulasi | Hashmi, Sana | Kumar, Ashok

Article Type: Research Article

Abstract: BACKGROUND: miRNAs play a crucial role in the genesis of cancer, either as tumor suppressor genes or as oncogenes. Single Nucleotide Polymorphisms (SNPs) in the seed region of microRNAs (miRNAs) can dysregulate their levels in the tissues and thereby affect carcinogenesis. The association of SNP in miR-146a (rs2910164) with the risk of oral squamous cell carcinoma (OSCC) has not been understood. OBJECTIVE: In the present study, we have determined the association and functional significance of miR-146a (rs2910164) SNP with susceptibility to OSCC predisposition. METHODS: In the present case-control study, we enrolled 430 subjects from …central India (215 OSCC cases and 215 healthy controls). We performed genotyping by Kompetitive Allele Specific PCR (KASP), and their correlation with OSCC susceptibility was analyzed. miRNA expression profiling in tumor tissues and adjacent normal tissues from six OSCC patients was done by a NanoString n-Counter-based assay. Subsequently, gene ontology and pathway analysis were performed with FunRich version 3.13. RESULTS: The CC genotype of rs2910164 miR-146a was significantly associated with the increased risk for OSCC (CC vs GC , OR = 2.62; 95% CI: 1.48–4.66; p value = 0.001). However, the GC genotype was protective with GC vs CC (OR = 0.38, 95%CI = 0.21–0.67, p -value = 0.001), and GC vs GG (OR = 0.58, 95%CI = 0.37–0.89, p -value = 0.01). CONCLUSION: Our finding suggests that SNP rs2910164 of miR-146a may be a genetic risk factor for OSCC susceptibility in the Central India population. However, more extensive multicenter studies are required to validate these findings. Show more

Keywords: Oral squamous cell carcinoma (OSCC), miRNA, single nucleotide polymorphism (SNP)

DOI: 10.3233/CBM-230064

Citation: Cancer Biomarkers, vol. 38, no. 2, pp. 203-214, 2023

Authors: Huang, Wenxi | Zeng, Zanwen | Xu, Yonghui | Mai, Zhibin

Article Type: Research Article

Abstract: BACKGROUND: Although exosomal microRNAs (exo-miRNAs) regulate angiogenesis, they are not sufficient for the development of anti-vascular drugs for tongue squamous cell carcinoma (TSCC). miR-205-5p is an exo-miRNA that is highly expressed in the saliva of patients with oral SCC. OBJECTIVE: We aimed to clarify the role and molecular mechanism of exosomal miR-205-5p in regulating TSCC angiogenesis. METHODS: Effect of exosomes derived from TSCC cells on human umbilical vein endothelial cell (HUVEC) function was determined using the CCK-8, Transwell, Transwell-Matrigel, and Matrigel-based tube formation assays. Protein levels were detected by western blot. The binding …between miR-205-5p and the 3 ′ UTR of AMOT was verified using a luciferase reporter assay. RESULTS: Exosomal miR-205-5p (exo-miR-205-5p) promoted the proliferation, migration, and invasion of HUVECs, increased the number of tubes formed by HUVECs, and increased the vascular endothelial growth factor receptor 2 levels in HUVECs. Exo-miR-205-5p downregulated the AMOT level in HUVECs. Results of the luciferase reporter assay showed that miR-205-5p could bind to the 3 ′ UTR of AMOT . AMOT overexpression blocked the effect of exo-miR-205-5p on HUVEC functions. CONCLUSION : Exo-miR-205-5p derived from TSCC regulates the angiogenic activity of HUVECs by targeting AMOT and might be a new molecular target for the development of anti-vascular drugs for TSCC. Show more

Keywords: Tongue squamous cell carcinoma, angiogenesis, exosomal miR-205-5p, HUVECs, AMOT

DOI: 10.3233/CBM-220350

Citation: Cancer Biomarkers, vol. 38, no. 2, pp. 215-224, 2023

Authors: Fang, Yuan | Tang, Weiqiang | Zhao, Dan | Zhang, Xiaoli | Li, Na | Yang, Yang | Jin, Li | Li, Zhitao | Wei, Benkai | Miao, Yinglei | Zeng, Zhong | Huang, Hanfei

Article Type: Research Article

Abstract: BACKGROUND: Lymphoid-specific helicase (HELLS), a SNF2-like chromatin-remodeling enzyme, plays a key role in tumor progression via its DNA methylation function. However, the effects of HELLS on immune infiltration and prognosis in liver hepatocellular carcinoma (LIHC) remain uncertain. METHODS: The Tumor Immune Estimation Resource (TIMER) database was employed to explore the pan-cancer mRNA expression of HELLS and its correlation with immunity. GEPIA2 was used to verify the correlation between HELLS expression and survival. The role of HELLS in cancer was explored via gene set enrichment analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) and the …construction of gene-gene and protein-protein interaction networks (PPI). Additionally, correlations between DNA methylation, HELLS expression, and immune-related genes were explored in LIHC. HELLS expression in LIHC clinical samples was determined using qRT-PCR and western blotting. The effects of downregulated HELLS expression in hepatocellular carcinoma cells was explored via transfection experiments in vitro . RESULTS: High HELLS mRNA expression was identified in several cancers and was significantly associated with poorer prognosis in LIHC. Furthermore, HELLS expression was positively correlated with tumor-infiltrating lymphocytes and immune checkpoint genes in LIHC. Bioinformatics analysis suggested that DNA methylation of HELLS may be associated with the immune response. Results from the TCGA-LIHC dataset, clinical samples, and functional analysis indicated that HELLS contributed to tumor progression in LIHC. CONCLUSION: The study findings demonstrate that HELLS is an important factor in promoting LIHC malignancy and might serve as a potential biomarker for LIHC. Show more

Keywords: HELLS, immune, tumor-infiltrating, prognosis, DNA methylation, liver hepatocellular carcinoma

DOI: 10.3233/CBM-230073

Citation: Cancer Biomarkers, vol. 38, no. 2, pp. 225-239, 2023

Authors: Mu, Jianhua | Gong, Jianan | Lin, Peng | Zhang, Mengzhen | Wu, Kai

Article Type: Research Article

Abstract: BACKGROUND: Immunometabolism plays an important role in neuroblastoma (NB). However, the mechanism of immune-metabolism related genes (IMRGs) in NB remains unclear. This study aimed to explore the effects of IMRGs on the prognosis, immune infiltration and stemness of patients with NB using machine learning methods. METHODS: R software (v4.2.1) was used to identify the differentially expressed IMRGs, and machine learning algorithm was used to screen the prognostic genes from IMRGs. Then we constructed a prognostic model and calculated the risk scores. The NB patients were grouped according to the prognosis scores. In addition, the genes most …associated with the immune infiltration and stemness of NB were analyzed by weighted gene co-expression network analysis (WGCNA). RESULTS: There were 89 differentially expressed IMRGs between the MYCN amplification and the MYCN non-amplification group, among which CNR1 , GNAI1 , GLDC and ABCC4 were selected by machine learning algorithm to construct the prognosis model due to their better prediction effect. Both the K-M survival curve and the 5-year Receiver operating characteristic (ROC) curve indicated that the prognosis model could predict the prognosis of NB patients, and there was significant difference in immune infiltration between the two groups according to the median of risk score. CONCLUSIONS: We verified the effects of IMRGs on the prognosis, immune infiltration and stemness of NB. These findings could provide help for predicting prognosis and developing immunotherapy in NB. Show more

Keywords: Neuroblastoma, immune, metabolism, prognosis, machine learning

DOI: 10.3233/CBM-230119

Citation: Cancer Biomarkers, vol. 38, no. 2, pp. 241-259, 2023

Authors: Zheng, Shaokai | Li, Ting | Qiu, Lianglin

Article Type: Research Article

Abstract: OBJECTIVE: Testicular germ cell tumors (TGCTs), containing pure seminoma and non-seminoma, occupy the most majority of testicular cancers in adolescents and young men, which has increased dramatically in recent decades. Therefore, it is important to find crucial genes for improving diagnosis and prognosis in TGCTs. However, the diagnostic and prognostic markers of TGCTs are limited. METHODS: In this study, our main objective is to explore novel potential genes that can be used as diagnostic and prognostic biomarkers in TGCTs. Our study detected 732 differentially expressed genes (DEGs) using three microarray expression profiling datasets from Gene Expression …Omnibus (GEO). Multiple analysis was performed to identify the roles of DEGs, including pathway and functional enrichment analysis, protein-protein interaction (PPI) network analysis, module analysis, and survival analysis. RESULT: In total, 322 upregulated genes and 406 downregulated genes were identified as DEGs The functional and pathway enrichment analysis shows that DEGs were highly enriched in multiple biological attributes such as T cell activation, reproduction in multicellular organism, sperm flagellum, antigen processing and presentation Then, seven potential crucial genes were identified via PPI network analysis, module analysis, and survival analysis. Furthermore, 7 potential crucial genes had shown to play a key role in regulating immune cell infiltration level in patients with TGCTs. CONCLUSION: We identified seven potential crucial genes (LAPTM5, NCF2, PECAM1, CD14, COL4A2, ANPEP and RGS1), which may be molecular markers in improving the way of diagnosis and prognosis in TGCTs. Show more

Keywords: Testicular germ cell tumors, biomarkers, gene expression, prognosis, immune cell infiltration

DOI: 10.3233/CBM-230095

Citation: Cancer Biomarkers, vol. 38, no. 2, pp. 261-272, 2023

Article Type: Correction

DOI: 10.3233/CBM-239002

Citation: Cancer Biomarkers, vol. 38, no. 2, pp. 273-273, 2023