Cancer Biomarkers - Volume 30, issue 1

Authors: Tong, Fei | Guo, Jun | Miao, Zhanqi | Li, Zhihua

Article Type: Research Article

Abstract: BACKGROUND: The prognosis of patients with recurrent and/or metastatic oral squamous cell carcinoma (OSCC) remains poor, and its incidence is especially high in developing countries. Multiple long non-coding RNAs (lncRNAs) are recently identified as crucial oncogenic factors or tumor suppressors. This study aimed to probe into the role of lncRNA small nucleolar RNA host gene 17 (SNHG17) on the progression of OSCC. METHODS: The expression level of SNHG17 in OSCC samples was tested using quantitative real-time polymerase chain reaction (qRT-PCR). Human OSCC cell lines CAL-27 and Tca8113 were used in in vitro studies. Cell counting …kit-8 (CCK-8) and BrdU assays were used to assess the effect of SNHG17 on OSCC cell proliferation. Flow cytometry was used to study the effect of SNHG17 on OSCC cell apoptosis. Transwell assay was conducted to detect the effect of SNHG17 on migration and invasion. Moreover, luciferase reporter assay was employed to confirm targeting relationship between miR-375 and SNHG17. Additionally, Western blot was used to observe the regulatory function of SNHG17 on PAX6. RESULTS: SNHG17 expression in OSCC clinical samples was significantly increased and was correlated with unfavorable pathological indexes. Its overexpression remarkably accelerated proliferation and metastasis of OSCC cells, while reduced apoptosis. Accordingly, knockdown of SNHG17 suppressed the malignant phenotypes of OSCC cells. Overexpression of SNHG17 significantly reduced the expression of miR-375 by sponging it, but enhanced the expression of PAX6. CONCLUSION: SNHG17 is a sponge of tumor suppressor miR-375 in OSCC, enhances the expression of PAX6 indirectly, and functions as an oncogenic lncRNA. Show more

Keywords: OSCC, SNHG17, miR-375, PAX6

DOI: 10.3233/CBM-191070

Citation: Cancer Biomarkers, vol. 30, no. 1, pp. 1-12, 2021

Authors: Chen, Heyan | Li, Kunlong | Li, Yijun | Xie, Peilin | He, Jianjun | Zhang, Huimin

Article Type: Research Article

Abstract: BACKGROUND: Cancer will become the leading cause of death worldwide in the 21st century, meanwhile, immunotherapy is the most popular cancer treatment method in recent years. COPI Coat Complex Subunit Beta 1 (COPB1) relates to human innate immunity. However, the role of COPB1 in pan-cancer remains unclear. OBJECTIVE: The purpose of this study was to explore the relationship between COPB1 mRNA expression and tumor infiltrating lymphocytes and immune examination sites in pan-cancer. METHODS: Data from multiple online databases were collected. The BioGPS, UALCAN Database, COSMIC, cBioPortal, Cancer Regulome tools, Kaplan-Meier Plotter and TIMER …website were utilized to perform the analysis. RESULTS: Upregulation of COPB1 has been widely observed in tumor tissues compared with normal tissues. Although COPB1 has poor prognosis in pan-cancer, COPB1 high expression was beneficial to the survival of ESCA patients. Unlike ESCA, COPB1 expression in STAD was positively correlated with tumor infiltrating lymphocytes, including B cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells. Finally, we also found that the expression of COPB1 in STAD was positively correlated with PD-L1 and CTLA4. CONCLUSIONS: COPB1 may be a prognostic biomarker for pan-carcinoma, and also provide an immune anti-tumor strategy for STAD based on the expression of COPB1. Show more

Keywords: COPB1, pan-cancer, survival analysis, immune infiltration, immune inhibitor

DOI: 10.3233/CBM-200398

Citation: Cancer Biomarkers, vol. 30, no. 1, pp. 13-27, 2021

Authors: Ning, Yuwen | Bai, Zhengfa

Article Type: Research Article

Abstract: Osteosarcoma (OS) is one of the most primary bone malignancies, often occurring in adolescents or children. Numerous scientific findings have introduced that long noncoding RNAs (lncRNAs) can be involved in tumor occurrence and development. Although DSCAM-AS1 has been studied in several cancers, its role and mechanism in OS are poorly understood. In this work, high level of DSCAM-AS1 was validated in OS cell lines. Depleting DSCAM-AS1 inhibited cell proliferation, migration and EMT process in OS. Subsequently, we disclosed that DSCAM-AS1 was mainly observed in the cytoplasm of OS cells and could bind with miR-186-5p in OS. Moreover, inhibiting miR-186-5p rescued …the impact of silenced DSCAM-AS1 on OS progression. Additionally, GPRC5A was verified as the target downstream of miR-186-5p, and it was negatively modulated by miR-186-5p but positively regulated by DSCAM-AS1. More importantly, DSCAM-AS1 enhanced GPRC5A level in OS by sequestering miR-186-5p. Finally, up-regulating GPRC5A reversed the influences of DSCAM-AS1 repression on the oncogenic behaviors of OS cells. Knockdown of DSCAM-AS1 suppressed NPC tumor growth in vivo . All findings uncovered that DSCAM-AS1 aggravated OS progression through sponging miR-186-5p to up-regulate GPRC5A expression. Thus, we proposed DSCAM-AS1 as a probable target for OS treatment. Show more

Keywords: DSCAM-AS1, miR-186-5p, GPRC5A, osteosarcoma

DOI: 10.3233/CBM-190703

Citation: Cancer Biomarkers, vol. 30, no. 1, pp. 29-39, 2021

Authors: Zou, Xuan | Xia, Tiansong | Li, Minghui | Wang, Tongshan | Liu, Ping | Zhou, Xin | Huang, Zebo | Zhu, Wei

Article Type: Research Article

Abstract: BACKGROUND: Circulating microRNAs (miRNAs) prove to be potential non-invasive indicators of cancers. The purpose of this study is to profile serum miRNA expression in breast cancer (BC) patients to find potential biomarkers for BC diagnosis. METHODS: The miRNA expression patterns of serum samples from 216 BC patients and 214 normal control subjects were compared. A four-phase validation was conducted for biomarker identification. In the screening phase, the Exiqon miRNA qPCR panel was employed to select candidates, which were further analyzed by quantitative reverse transcriptase PCR in the following training, testing, and external validation phases. …RESULTS: A 12-miRNA (let-7b-5p, miR-106a-5p, miR-19a-3p, miR-19b-3p, miR-20a-5p, miR-223-3p, miR-25-3p, miR-425-5p, miR-451a, miR-92a-3p, miR-93-5p, and miR-16-5p) panel in serum was constructed. The diagnostic performance of the panel was assessed using ROC curve analyses. The area under the curves (AUCs) were 0.952, 0.956, 0.941 and 0.950 for the four separate phases, respectively. Additionally, the expression features of the 12 miRNAs were further explored in 32 pairs of BC tumor and para-tumor tissues, and 32 pairs of serum exosomes samples from patients and healthy subjects. miR-16-5p, miR-106a-5p, miR-25-3p, miR-425-5p, and miR-93-5p were highly overexpressed and let-7b-5p was conversely downregulated in tumor tissues. Excluding miR-20a-5p and miR-223-3p, the 10 other miRNAs were all significantly upregulated in BC serum-derived exosomes. CONCLUSION: A signature consisting of 12 serum miRNAs was identified and showed potential for use in non-invasive diagnosis of BC. Show more

Keywords: Serum microRNA, breast cancer, biomarker, qRT-PCR, exosomes

DOI: 10.3233/CBM-201547

Citation: Cancer Biomarkers, vol. 30, no. 1, pp. 41-53, 2021

Authors: Kolapalli, Srinivasa Prasad | Kumaraswamy, Sunil B. | Mortha, Karuna Kumar | Thomas, Anil | Banerjee, Shib Das

Article Type: Research Article

Abstract: Colorectal cancer (CRC) is the third most common cancer; cancer biomarker discovery is important for disease detection and management. It is known that hyaluronic acid and its receptors are ubiquitously expressed in almost all human tissues. Earlier we have shown that a monoclonal antibody H11B2C2, presently known as UNIVmAb, reactive hyaladherin expressed in multiple human cancers mainly using immunohistochemistry. However, the nature of the antigen and its sequence homology are not known. In the current study, a comprehensive investigation was performed to explore the nature of the antigen and its homology using both biochemical and proteomic analysis. Our results showed …that UNIVmAb reactive 57 kDa antigen was overexpressed in advanced grade colorectal cancer tissues compared to benign and its hyperplasia. Biochemical investigations including biotinylated hyaluronic acid-pulldown, Immunoprecipitation, HA-oligo competition experiments confirmed that the UNIVmAb reactive 57 kDa antigen is a member of hyaladherin. Further Proteomic analysis showed that the antigen has homology with IGHG1 (Igγ -1 chain C region), a possible IgG superfamily, and is associated with human serum albumin. Show more

Keywords: Colorectal cancer (CRC), UNIVmAb, hyaladherin (HD), hyaluronic acid-binding protein (HABP), hyaluronic acid (HA), extracellular matrix (ECM), immunoglobulin superfamily (IgSF)

DOI: 10.3233/CBM-191260

Citation: Cancer Biomarkers, vol. 30, no. 1, pp. 55-62, 2021

Authors: Lee, Nan | Xia, Xuelian | Meng, Hui | Zhu, Weiliang | Wang, Xiankai | Zhang, Tianyuan | Zhang, Chanyuan | Zhang, Jian | Luo, Peng

Article Type: Research Article

Abstract: BACKGROUND: DNA methylation plays a vital role in modulating genomic function and warrants evaluation as a biomarker for the diagnosis and treatment of lung squamous cell carcinoma (LUSC). OBJECTIVE: In this study, we aimed to identify effective potential biomarkers for predicting prognosis and drug sensitivity in LUSC. METHODS: A univariate Cox proportional hazards regression analysis, a random survival forests-variable hunting (RSFVH) algorithm, and a multivariate Cox regression analysis were adopted to analyze the methylation profile of patients with LUSC included in public databases: The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO). …RESULTS: A methylated region consisting of 3 sites (cg06675147, cg07064331, cg20429172) was selected. Patients were divided into a high-risk group and a low-risk group in the training dataset. High-risk patients had shorter overall survival (OS) (hazard ratio [HR]: 2.72, 95% confidence interval [CI]: 1.82–4.07, P < 0.001) compared with low-risk patients. The accuracy of the prognostic signature was validated in the test and validation cohorts (TCGA, n = 94; GSE56044, n = 23). Gene set variation analysis (GSVA) showed that activity in the cell cycle/mitotic, ERBB, and ERK/MAPK pathways was higher in the high-risk compared with the low-risk group, which may lead to differences in OS.Interestingly, we observed that patients in the high-risk group were more sensitive to gemcitabine and docetaxel than the low-risk group, which is consistent with results of the GSVA. CONCLUSION: We report novel methylation sites that could be used as powerful tools for predicting risk factors for poorer survival in patients with LUSC. Show more

Keywords: Lung squamous cell carcinoma, methylated sites, overall survival, prognosis, signature

DOI: 10.3233/CBM-201564

Citation: Cancer Biomarkers, vol. 30, no. 1, pp. 63-73, 2021

Authors: Zweerink, Susanne | Mesghenna, Senait | Mueck, Vera | Schulte, Sigrid | Kuetting, Fabian | Quaas, Alexander | Goeser, Tobias | Nierhoff, Dirk

Article Type: Research Article

Abstract: BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide and the search for clinically useful biomarkers is ongoing. Neighbor of Punc E11 (NOPE) is an established biomarker of murine HCC that remains undetectable in normal liver and at preneoplastic stages. OBJECTIVE: The aim of our study was to evaluate the presence of NOPE in human HCC. METHODS: Histologically confirmed HCC and corresponding non-tumor liver samples from 20 patients were analyzed for expression of NOPE using qRT-PCR and mRNA-in-situ technology in a conserved tissue context. RESULTS: …In our cohort, 30% of HCC samples were expressing NOPE which proved particularly useful in non-cirrhotic HCC samples with up to 155-fold higher expression than in adult liver. Using mRNA-in-situ technology, NOPE was clearly identified within epithelial tumor cells of NOPE positive human HCCs. In our analyzed cohort, the combination of AFP with NOPE did not reach more than 40% sensitivity while GPC-3 and NOPE were complementary to each other reaching a combined sensitivity of 85.7%. CONCLUSIONS: This is the first characterization of NOPE as a potential biomarker for human HCC. Our results underline the value of NOPE as a complementing biomarker for human HCC. Show more

Keywords: Human HCC, biomarker, IGDCC4, mRNA-in situ technology, AFP, GPC-3

DOI: 10.3233/CBM-190819

Citation: Cancer Biomarkers, vol. 30, no. 1, pp. 75-83, 2021

Authors: Tang, Yaoxiang | Yang, Yang | Luo, Jiadi | Liu, Sile | Zhan, Yuting | Zang, Hongjing | Zheng, Hongmei | Zhang, Yuting | Feng, Juan | Fan, Songqing | Wen, Qiuyuan

Article Type: Research Article

Abstract: BACKGROUND: HSP60 and its partner HSP10 are members of heat shock proteins (HSPs) family, which help mitochondrial protein to fold correctly. Mcl-1, a member of the Bcl-2 family, plays a crucial role in regulation of cell apoptosis. Aberrant expression of HSP10, HSP60 and Mcl-1 is involved in the development of many tumors. OBJECTIVE: To examine the association between expression of HSP10, HSP60 and Mcl-1 and clinicopathological features of non-small cell lung cancer (NSCLC). METHODS: Tissue microarrays including 53 non-cancerous lung tissues (Non-CLT) and 354 surgically resected NSCLC were stained with anti-HSP10, anti-HSP60 and …anti-Mcl-1 antibodies respectively by immunohistochemistry. RESULTS: Higher expression of HSP10, HSP60 and Mcl-1 was found in NSCLC compared with Non-CLT. Both individual and combined HSP10 and HSP60 expression in patients with clinical stage III was higher than that in stage I ∼ II. Expression of HSP10 showed a positive correlation with HSP60 and Mcl-1. Overall survival time of NSCLC patients was remarkably shorter with elevated expression of HSP10, HSP60 and Mcl-1 alone and in combination. Moreover overexpression of HSP10 and Mcl-1 was poor independent prognostic factor for lung adenocarcinoma patients. CONCLUSIONS: High expression of HSP10, HSP60 and Mcl-1 might act as novel biomarker of poor prognosis for NSCLC patients. Show more

Keywords: HSP10, HSP60, Mcl-1, NSCLC, prognosis

DOI: 10.3233/CBM-200410

Citation: Cancer Biomarkers, vol. 30, no. 1, pp. 85-94, 2021

Authors: Sirotković-Skerlev, Maja | Plavetić, Natalija Dedić | Sedlić, Filip | Kuna, Sanja Kusačić | Vrbanec, Damir | Belev, Borislav | Pleština, Stjepko | Kovač, Zdenko | Kulić, Ana

Article Type: Research Article

Abstract: BACKGROUND: Apoptosis inhibition is a major tumorigenic factor. Bcl-2 dysregulation and TP53 mutation status, which may correlate with autoantibody generation, contribute to impaired apoptosis. OBJECTIVE: This study aimed to investigate the prognostic value of circulating Bcl-2 and anti-p53 antibodies (p53Abs) in a 17.5-year follow-up of breast cancer patients. We also analyzed the correlations of Bcl-2 and p53Abs with various clinicopathological parameters in order to assess their impact on tumor aggressiveness. METHODS: Serum Bcl-2 and p53Abs levels were analyzed by the enzyme-linked immunosorbent assay (ELISA) in 82 patients with invasive breast cancer and twenty …individuals without malignancy. RESULTS: Serum Bcl-2 and p53Abs levels in breast cancer patients were significantly higher than those in controls. Patients with high levels of Bcl-2 (cut-off 200 U/ml) had a poorer prognosis (17.5-year survival) than those with lower Bcl-2 values. In combined analysis the subgroup of patients with elevated p53Abs (cut-off 15 U/ml) and elevated Bcl-2 (cut-offs 124 U/ml and 200 U/ml) had the worse prognosis in 17.5-year survival. In correlation analysis p53Abs and Bcl-2 were associated with unfavorable clinicopathological parameters. CONCLUSIONS: Our results suggest that breast cancer patients with high serum levels of p53Abs and Bcl-2 present an especially unfavorable group in a long follow-up. Show more

Keywords: Breast cancer, Bcl-2, anti-p53 antibodies, ELISA, survival

DOI: 10.3233/CBM-201497

Citation: Cancer Biomarkers, vol. 30, no. 1, pp. 95-104, 2021

Authors: Zeng, Qingwen | Li, Leyan | Feng, Zongfeng | Luo, Lianghua | Xiong, Jianbo | Jie, Zhigang | Cao, Yi | Li, Zhengrong

Article Type: Research Article

Abstract: BACKGROUND: Previous studies have identified LCP1 as a diagnostic and prognostic marker in several cancers. However, the role of LCP1 in gastric cancer (GC) and its effect on tumor immune infiltration remain unclear. OBJECTIVE: The aim was to explore the role of LCP1 in GC and its effect on tumor immune infiltration. METHODS: We explored the expression of LCP1 relative to clinicopathology in GC patients by bioinformatics analysis and immunohistochemistry. Using cBioportal database, we analyzed the characteristic genetic variations of LCP1 in GC. In addition, we evaluated the …correlation between LCP1 expression and tumor-infiltrating lymphocytes (TILs) using R software, TIMER and TISIDB databases. Finally, we analyzed the biological functions in which LCP1 may participate and the signaling pathways it may regulate. RESULTS: Here, we showed that LCP1 expression is significantly correlated with tumor aggressiveness and poor prognosis in GC patients. Additionally, the results indicated that LCP1 was associated with TILs, including both immunosuppressive and immunosupportive cells, and was strongly correlated with various immune marker sets in GC. GSEA analysis demonstrated that LCP1 expression played an important role in lymphocyte formation and immune reaction. CONCLUSIONS: LCP1 may be a potential prognostic biomarker for GC patients and a marker for tumor immunotherapy. Show more

Keywords: LCP1, gastric cancer, prognosis, immune infiltrates

DOI: 10.3233/CBM-200006

Citation: Cancer Biomarkers, vol. 30, no. 1, pp. 105-125, 2021

Authors: Pei, Li-Juan | Sun, Peng-Jun | Ma, Kui | Guo, Yan-Yan | Wang, Ling-Yan | Liu, Fei-De

Article Type: Research Article

Abstract: Gastric cancer (GC) remains poor prognosis and survival issues due to the resistance of chemotherapies, such as cisplatin. The long non-coding RNA small nucleolar RNA host gene 7 (lncRNA-SNHG7) is known as an oncogenic molecule in diverse cancers. Here, we demonstrate that SNHG7 was significantly upregulated in gastric cancer and positively correlated with cisplatin resistance of gastric cancer cells that SNHG7 was significantly upregulated in cisplatin resistant cells. Silencing SNHG7 dramatically sensitized cisplatin resistant cells. In contrast, a negative correlation between lncRNA-SNHG7 and miR-34a was found that miR-34a was downregulated in gastric cancer patient tissues and significantly sensitized cisplatin resistant …gastric cancer cells. Intriguingly, bioinformatical analysis indicated miR-34a has putative biding site for SNHG7 and such negative association between SNHG7 and miR-34a was verified in gastric cancer tissues. The cisplatin resistant cells displayed increased glycolysis rate and SNHG7 promoted cellular glycolysis rate of gastric cancer cells. Luciferase assay illustrated LDHA, a glycolysis enzyme, was the direct target of miR-34a. Importantly, inhibiting SNHG7 successfully suppressed LDHA expressions and sensitized cisplatin resistant cells and such inhibitory effects could be recovered by further anti-miR-34a. These findings suggest an important regulator mechanism for the SNHG7-mediated cisplatin resistance via miR-34a/LDHA-glycolysis axis. Show more

Keywords: Gastric cancer, lncRNA-SNHG7, miR-34a, cisplatin resistance, Warburg effect

DOI: 10.3233/CBM-201621

Citation: Cancer Biomarkers, vol. 30, no. 1, pp. 127-137, 2021