Cancer Biomarkers - Volume 35, issue 4

Authors: Pan, Li-Na | Ma, Yun-Fang | Hu, Jia-An | Xu, Zhi-Hong

Article Type: Research Article

Abstract: Circular RNA (circRNA) has been shown to participate in various tumors, including lung cancer. In the present study, we explored the expression and functional relevance of hsa_circ_0003288 in human non-small cell lung cancer (NSCLC). We verified that hsa_circ_0003288 expression was upregulated in lung cancer tissues and cell lines. Overexpression of hsa_circ_0003288 dramatically promoted lung cancer cell proliferation, colony formation, inhibited apoptosis, and increased cell migration and invasion in vitro . Xenograft experiments showed that hsa_circ_0003288 overexpression accelerated tumor growth in vivo . Mechanistically, hsa_circ_0003288 negatively regulated miR-145 to exert the oncogenic role in lung cancer. Overexpression of miR-145 decreased cell …proliferation, induced apoptosis, and suppressed migration and invasion in lung cancer. Additionally, miR-145 co-transfection abolished the oncogenic role of hsa_circ_0003288. Collectively, these findings identified a novel regulatory role of hsa_circ_0003288/miR-145 axis in the progression of NSCLC. Show more

Keywords: Non-small cell lung cancer, hsa_circ_0003288, miR-145

DOI: 10.3233/CBM-203198

Citation: Cancer Biomarkers, vol. 35, no. 4, pp. 349-357, 2022

Authors: Akbari, Abolfazl | Abbasi, Somayeh | Borumandnia, Nasrin | Eshkiki, Zahra Shokati | Sedaghat, Meghdad | Tabaeian, Seidamir Pasha | Kashani, Amirhossein Faghihi | Talebi, Atefeh

Article Type: Research Article

Abstract: Long noncoding RNAs (lncRNAs), as well-known modulator of the epigenetic processes, have been shown to contribute to normal cellular physiological and pathological conditions such as cancer. Through the interaction with epigenetic regulators, an aberrant regulation of gene expression can be resulted due to their dysregulation, which in turn, can be involved in tumorigenesis. In the present study, we reviewed the lncRNAs’ function and mechanisms that contributed to aberrant epigenetic regulation, which is directly related to gastrointestinal cancer (GI) development and progression. Findings indicated that epigenetic alterations may involve in tumorigenesis and are valuable biomarkers in case of diagnosing, assessing of …risk factors, and predicting of GI cancers. This review summarized the accumulated evidence for biological and clinical application to use lncRNAs in GI cancers, including colorectal, gastric, oral, liver, pancreatic and oesophageal cancer. Show more

Keywords: Chemoresistance, epigenetic, gastrointestinal cancer, long non-coding RNA, metastasis

DOI: 10.3233/CBM-220142

Citation: Cancer Biomarkers, vol. 35, no. 4, pp. 359-377, 2022

Authors: Chen, Heyan | Pu, Shengyu | Mei, Nan | Liu, Xiaoxu | He, Jianjun | Zhang, Huimin

Article Type: Research Article

Abstract: BACKGROUND: Intercellular adhesion molecules (ICAMs) in the tumor microenvironment are closely related to immunity and affect the prognosis of cancer patients. OBJECTIVE: The aim of our study is to explore the correlation between ICAM expression, mutation, methylation and immunity and their prognostic value in breast cancer (BC) is not clear. METHODS: Online databases and tools such as UALCAN, COSMIC, cBioPortal, MethSurv, PrognoScan, Kaplan-Meier Plotter, GSCA and TIMER were utilized in this study. RESULTS: We found that the mRNA and protein expression levels of ICAM1 were upregulated in triple-negative breast cancer …(TNBC) compared with normal tissues, and TNBC patients with high expression of ICAM1 had better overall survival (OS) and recurrence-free survival (RFS). The main types of ICAM1 gene variants were missense mutation and amplification, and ICAM1 showed a lower level of methylation in TNBC cancer tissues than in normal tissues, which was contrary to the high expression levels of ICAM1 mRNA and protein. Next, the function of ICAM1 was mainly related to the activation of apoptosis, epithelial-mesenchymal transition (EMT) and inhibition of the androgen receptor (AR) and estrogen receptor (ER) pathways. Meanwhile, functional pathway enrichment results showed that ICAM1 was also involved in the immune regulation process of BC. Furthermore, the expression of ICAM1 was positively associated with 6 types of tumor-infiltrating immune cells (CD8+ T cells, CD4+ T cells, B cells, neutrophils, macrophages and dendritic cells) and was also positively related to the expression of programmed cell death-1 (PD-1), programmed cell death-ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA4). CONCLUSIONS: Our research indicated that ICAM1 was likely to be a potential therapeutic target in TNBC. Show more

Keywords: Breast cancer, ICAMs, prognostic biomarkers, immune checkpoint therapy, tumor microenvironment

DOI: 10.3233/CBM-220073

Citation: Cancer Biomarkers, vol. 35, no. 4, pp. 379-393, 2022

Authors: Peng, Shuang | Liu, Cheng | Fan, Xingchen | Zhu, Jingfeng | Zhang, Shiyu | Zhou, Xin | Wang, Tongshan | Gao, Feng | Zhu, Wei

Article Type: Research Article

Abstract: BACKGROUND: MicroRNAs (miRNAs) capable of post-transcriptionally regulating mRNA expression are essential to tumor occurrence and progression. OBJECTIVE: This study aims to find negatively regulatory miRNA-mRNA pairs in prostate adenocarcinoma (PRAD). METHODS: Combining The Cancer Genome Atlas (TCGA) RNA-Seq data with Gene Expression Omnibus (GEO) mRNA/miRNA expression profiles, differently expressed miRNA/mRNA (DE-miRNAs/DE-mRNAs) were identified. MiRNA-mRNA pairs were screened by miRTarBase and TarBase, databases collecting experimentally confirmed miRNA-mRNA pairs, and verified in 30 paired prostate specimens by real-time reverse transcription polymerase chain reaction (RT-qPCR). The diagnostic values of miRNA-mRNA pairs were measured by receiver operation …characteristic (ROC) curve and Decision Curve Analysis (DCA). DAVID-mirPath database and Connectivity Map were employed in GO/KEGG analysis and compounds research. Interactions between miRNA-mRNA pairs and phenotypic features were analyzed with correlation heatmap in hiplot. RESULTS: Based on TCGA RNA-Seq data, 22 miRNA and 14 mRNA GEO datasets, 67 (20 down and 47 up) miRNAs and 351 (139 up and 212 down) mRNAs were selected. After screening from 2 databases, 8 miRNA (up)-mRNA (down) and 7 miRNA (down)-mRNA (up) pairs were identified with Pearson’s correlation in TCGA. By external validation, miR-221-3p (down)/GALNT3 (up) and miR-20a-5p (up)/FRMD6 (down) were chosen. The model combing 4 signatures possessed better diagnostic value. These two miRNA-mRNA pairs were significantly connected with immune cells fraction and tumor immune microenvironment. CONCLUSIONS: The diagnostic model containing 2 negatively regulatory miRNA-mRNA pairs was established to distinguish PRADs from normal controls. Show more

Keywords: miRNA, miRNA-mRNA networks, prostate adenocarcinoma, TCGA, PCR

DOI: 10.3233/CBM-220051

Citation: Cancer Biomarkers, vol. 35, no. 4, pp. 395-407, 2022

Authors: Kim, Guen Hui | Kim, Joyce Mary | Jee, Sun Ha | Jung, Keum Ji

Article Type: Research Article

Abstract: BACKGROUND: Nicotine metabolite ratio (NMR) can be used to predict total nicotine clearance. However, it is unknown whether NMR could be used as a marker of lung cancer risk. OBJECTIVE: To evaluate the blood metabolites of nicotine relating to the risk of developing lung cancer and investigate the combined effects of NMR and cigarette per day on the risk of lung cancer. METHODS: Among the 1,054 eligible subjects from the Korean Cancer Prevention Study-II biobank cohort, those with cotinine values below 0 ng/ml were excluded. Slow and fast metabolizer groups were defined using …the median value of the NMR, calculated with the control group data, as the cut-point. RESULTS: The multivariable Cox proportional hazard models demonstrated that, the fast metabolizer group had a significantly higher risk of lung cancer than the slow metabolizer group (Adjusted HR: 2.02, 95% CI: 1.32–3.10). Fast metabolizers who smoked more than 15 cigarettes per day had an even higher risk of lung cancer (Adjusted HR: 3.51, 95% CI: 1.96–6.29) than the slow metabolizers who smoked less than 15 cigarettes per day. CONCLUSIONS: In summary, the NMR may be an effective marker for estimating tobacco-related disease risks such as lung cancer. Show more

Keywords: Lung cancer, nicotine metabolite ratio, cotinine, smoking, biomarkers

DOI: 10.3233/CBM-220023

Citation: Cancer Biomarkers, vol. 35, no. 4, pp. 409-417, 2022

Authors: Liu, Zeng-Yao | Xing, Zhao-Hui | Wang, Wen | Liu, Yu-Xi | Wang, Rui-Tao | Li, Jia-Yu

Article Type: Research Article

Abstract: BACKGROUND: Post-hepatectomy liver failure (PHLF) is a severe complication of liver surgery in hepatocellular carcinoma (HCC) patients. Reduced lean body mass (LBM) decreases the immune activity and increases adverse clinical outcomes among cancer patients. OBJECTIVE: We aimed to assess the association between LBM and PHLF in HCC patients. METHODS: PHLF was defined and graded based on the International Study Group of Liver Surgery (ISGLS) criteria. Patients with Grade B or Grade C were included in PHLF ⩾ Grade B group, while others in PHLF < Grade B …group. LBM was measured via preoperative computed tomography images. Binary logistic regression was applied for investigating the association between LBM and PHLF. The receiver operating characteristic curve was used to identify potential cut-off values and assess the predictive ability of the measured variables. RESULTS: The PHLF ⩾ Grade B group had significantly lower LBM levels (means ± standard deviation: 57.0 ± 14.1) than PHLF < Grade B group (67.2 ± 15.7) (p < 0.001). After controlling other variables, LBM was an independent protective factor for PHLF ⩾ Grade B (Odds Ratio: 0.406, 95% confidence interval: 0.172–0.957, p = 0.039). The prevalence of PHLF ⩾ Grade B in each quartile of LBM was 29.4% (15/51), 25.5% (13/51), 19.2% (10/52) and 4.0% (2/50), respectively (p trend < 0.001). CONCLUSIONS: LBM might be a protective factor for PHLF in HCC patients. Our findings might help to develop a novel strategy to reduce the occurrence of hepatic dysfunction following major liver resection. Multicentric prospective studies and further molecular biologic investigation are needed. Show more

Keywords: Hepatocellular carcinoma, postoperative, liver failure, lean body mass, liver resection

DOI: 10.3233/CBM-220172

Citation: Cancer Biomarkers, vol. 35, no. 4, pp. 419-427, 2022

Authors: Chen, Changbao | Zhou, Hua | Zhang, Xiaolin | Liu, Zhongjun | Ma, Xinlong

Article Type: Research Article

Abstract: INTRODUCTION: The E3 ubiquitin ligase FBXW11 exerts an oncogenic or tumor suppressive function in a cellular context-dependent manner. However, the clinical significance and biological role of FBXW11 in chondrosarcoma have not been clearly characterized. This study focuses on the expression profile, prognostic value and biological function of FBXW11 in chondrosarcoma. METHODS: FBXW11 expression was analyzed by qRT-PCR and Western blot in six cases of chondrosarcoma specimens and the matched adjacent non-tumor tissues. The expression profile and prognostic value of FBXW11 were investigated in sixty-three cases of chondrosarcoma patients. Cell viability, colony formation, migration, invasion and apoptosis …assays were further detected in SW1353 chondrosarcoma cells with restored FBXW11 expression. RESULTS: Downregulation of FBXW11 was remarkably detected in human chondrosarcoma specimens compared with the corresponding non-tumor tissues and benign cartilage tumors. Downregulated FBXW11 expression significantly correlated with high-grade chondrosarcoma and poor prognosis. Furthermore, FBXW11 was identified as an independent prognostic factor for the overall survival of chondrosarcoma patients. Restored expression of FBXW11 significantly suppressed chondrosarcoma cell growth and induced apoptosis. CONCLUSIONS: These findings establish that FBXW11 was markedly downregulated and recognized as an independent prognostic factor for patients with chondrosarcoma, and restored FBXW11 expression can suppress chondrosarcoma growth and induce apoptosis, highlighting a novel biological marker and potential therapeutic target against chondrosarcoma. Show more

Keywords: FBXW11, chondrosarcoma development, cell growth, biological marker, therapeutic target

DOI: 10.3233/CBM-210426

Citation: Cancer Biomarkers, vol. 35, no. 4, pp. 429-437, 2022

Authors: Liu, Hengrui | Li, Yixue

Article Type: Research Article

Abstract: BACKGROUND: It is of great clinical significance to discover novel biomarkers for neck squamous cell carcinoma (HNSCC) treatments. We discovered a potential cancer-related gene, Cornichon Family AMPA Receptor Auxiliary Protein 4 (CNIH4), that can be a biomarker for HNSCC. METHODS: We access multiple open databases and analyzed bulk mRNA-sequencing, protein staining, and single-cell mRNA-sequencing data of HNSCC and investigated the diagnostic and prognostic value of CNIH4 in HNSCC. The potential association between CNIH4 and the immune microenvironment of HNSCC was also estimated. RESULTS: CNIH4 was significantly up-regulated in HNSCC compared with non-cancer tissues. …Higher CNIH4 resulted in a shorter overall survival time and we further constructed a survival nomogram for clinical applications. 2012 and 421 genes were identified as positive and negative differentially expressed genes of CNIH4 in HNSCC respectively. These genes were mostly mapped to “Cell cycle”, “DNA replicate”, “Cytokine-cytokine receptor interaction” KEGG pathways. Functions associated with CNIH4 were “stemness”, “cell cycle”, and “DNA repair” in single-cell data. CNIH4 potentially affected immune cell infiltration levels and cancer immune therapy. CONCLUSION: CNIH4 is a potential diagnostic and prognostic biomarker associated with cancer stemness and immunity in HNSCC. Show more

Keywords: CNIH4, HNSCC, cancer stemness; immunity

DOI: 10.3233/CBM-220143

Citation: Cancer Biomarkers, vol. 35, no. 4, pp. 439-450, 2022