Cancer Biomarkers - Volume 37, issue 1

Authors: Lin, Yihong | Yu, Xiongbin | Lu, Linbin | Chen, Hong | Wu, Junxian | Chen, Yaying | Lin, Qin | Wang, Xuewen | Chen, Xi | Chen, Xiong

Article Type: Research Article

Abstract: BACKGROUND: The optimal timing of combined chemotherapy with radiotherapy for locally advanced nasopharyngeal carcinoma (LA-NPC) is undetermined. OBJECTIVE: This study aimed to compare the therapeutic efficacy of neoadjuvant chemotherapy (NACT) followed by radiotherapy (RT) and concurrent chemoradiotherapy (CCRT). METHODS: Five hundred and thirty-eight patients diagnosed with LA-NPC and treated with NACT + RT or CCRT alone were enrolled in the study. Restricted cubic spline regression (RCS) was used to determine the relationship between age and the hazard Ratio of death. A Kaplan-Meier analysis was performed to evaluate overall survival (OS) …related to NACT + RT or CCRT alone. Cox proportional hazards models were used to adjust for potential confounding factors. RESULTS: Compared with the CCRT alone regimen, the NACT + RT regimen showed a significantly better OS rate with a 62% decreased risk of death in a subgroup of patients aged ⩾ 45 years (hazard ratio, HR: 0.38; 95% confidence interval, CI: 0.24–0.61). In patients aged < 45 years, the risk of death was significantly increased when NACT + RT was chosen compared with CCRT (HR: 4.10; 95% CI: 2.09–8.07). CONCLUSIONS: Age is a significant biomarker when selecting NACT + RT or CCRT alone in patients with locally advanced NPC. Show more

Keywords: Nasopharyngeal carcinoma, neoadjuvant chemotherapy, radiotherapy, concurrent chemoradiotherapy, age

DOI: 10.3233/CBM-210357

Citation: Cancer Biomarkers, vol. 37, no. 1, pp. 1-11, 2023

Authors: Liu, Yanqing | Jiang, Jianshuai

Article Type: Research Article

Abstract: BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most serious malignant tumors with a poor prognosis worldwide. Cuproptosis is a novel copper-dependent cell death form, involving mitochondrial respiration and lipoylated components of the tricarboxylic acid (TCA) cycle. Long non-coding RNAs (lncRNAs) have been demonstrated to affect the tumorigenesis, growth, and metastasis of HCC. OBJECTIVE: We explored the potential roles of cuproptosis-related lncRNAs in predicting the prognosis for HCC. METHODS: The RNA-seq transcriptome data, mutation data, and clinical information data of HCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The least …absolute shrinkage and selection operator (LASSO) algorithm and Cox regression analyses were performed to identify a prognostic cuproptosis-related lncRNA signature. The receiver operating characteristic (ROC) analysis was used to evaluate the predictive value of the lncRNA signature for HCC. The enrichment pathways, immune functions, immune cell infiltration, tumor mutation burden, and drug sensitivity were also analyzed. RESULTS: We constructed a prognostic model consisting of 8 cuproptosis-related lncRNAs for HCC. The patients were divided into high-risk group and low-risk group according to the riskscore calculated using the model. Kaplan-Meier analysis revealed that the high-risk lncRNA signature was correlated with poor overall survival [hazard ratio (HR) = 1.009, 95% confidence interval (CI) = 1.002–1.015; p = 0.010)] of HCC. A prognostic nomogram incorporated the lncRNA signature and clinicopathological features were constructed and showed favorable performance for predicting prognosis of HCC patients. In addition, the most immune-related functions were significantly different between the high-risk and low-risk groups. Tumor mutation burden (TMB) and immune checkpoints were also expressed differently between the two risk groups. Finally, HCC patients with low-risk score were more sensitive to several chemotherapy drugs. CONCLUSIONS: The novel cuproptosis-related lncRNA signature could be used to predict prognosis and evaluate the effect of chemotherapy for HCC. Show more

Keywords: Hepatocellular carcinoma, cuproptosis, lncRNAs, prognosis, immune checkpoint

DOI: 10.3233/CBM-220259

Citation: Cancer Biomarkers, vol. 37, no. 1, pp. 13-26, 2023

Authors: Jiao, Yuwen | Fu, Yue | Gong, Yu | Wang, Guangyao | Chen, Shuai | Cai, Gengdi | Wu, Siyuan | Tang, Liming

Article Type: Research Article

Abstract: BACKGROUND: Gastric cancer (GC) remains a huge challenge to the heathy of human beings, largely due to lacking of effective therapeutic measures. Though an oncogenic role for circular RNAs (circRNAs) circ_0067997 in the progression of GC has been described recently, the molecular modulatory mechanism of it still remains to be further explored. The aim of present study is to examine the molecular network of circ_0067997 in GC. METHODS: qRT-PCR was carried out to determine the mRNA levels of circ_0067997, miR-615-5p and AKT1 in cisplatin (DDP)-insensitive or sensitive GC tumor tissues and cells, while the correlations among …the contents of these molecules were determined by statistical analysis. The expression of circ_0067997 was manipulated by short-hairpin RNA and lentiviral-mediated approaches, while that of miR-615-5p was achieved by the application of its inhibitor or mimic. The in vivo action of circ_0067997 on tumor formation was determined by measuring tumor weight/volume/size and analyzing tumor apoptosis through TUNEL staining in mouse xenograft model and, while the in vitro effects of this circRNA and its target miR-615-5p on the cell survival and death were separately evaluated by CCK-8 assay and flow cytometry. Additionally, luciferase reporter assays were executed to determine the sequentially regulatory relationships of circ_0067997, miR-615-5p, and AKT1. RESULTS: Our data demonstrated that the level of circ_0067997 level was increased in DDP-insensitive GC tissues and cell line, while miR-615-5p presented the opposite results. Moreover, the relationships between circ_0067997 and miR-615-5p levels, circ_0067997 and AKT1 contents presented negative and positive correlations in clinic samples, respectively. Importantly, circ_0067997 was found to repress miR-615-5p expression, consequently leading to increased growth while reduced apoptosis of GC cells in the presence of DDP. Furthermore, the validated sequential regulation was circ_0067997 modulating miR-615-5p adjusting AKT1. CONCLUSIONS: This study demonstrated that circ_0067997 functioned as a sponge of miR-615-5p to target AKT1 expression, thereby enhancing the growth and restricting the apoptosis of DDP-insensitive GC cells. These new findings offered a valuable target for the detection and management of GC. Show more

Keywords: Circ_0067997, Cell proliferation and apoptosis, gastric cancer, Cisplatin (DDP), miR-615-5p/AKT1 axis

DOI: 10.3233/CBM-220145

Citation: Cancer Biomarkers, vol. 37, no. 1, pp. 27-38, 2023

Authors: Li, Liang | Wang, Nan | Wang, Jun | Li, Jiangang

Article Type: Research Article

Abstract: OBJECTIVE: This study attempts to investigate whether hsa_circRNA_001859 (circ_001859) could regulate the proliferation and invasion of pancreatic cancer through the miR-21-5p/SLC38A2 pathway. METHODS: GSE79634 microarray was analyzed with R package. The expression of circ_001859 in pancreatic cancer tissues and cells was verified by qRT-PCR. After the overexpression of circ_001859, cell proliferation, cell migration and invasion were verified by colony formation and transwell assay. The targeting relationship between miR-21-5p and circ_001859 was predicted by TargetScan and was verified by dual luciferase reporter assay, RNA pull down and qRT-PCR. The effect of miR-21-5p on cell proliferation, migration and …invasion were investigated by colony formation and transwell assay respectively. Similarly, the targeting relationship between miR-21-5p and SLC38A2 was predicted by TargetScan and was verified by dual luciferase reporter assay, western blot and qRT-PCR. The effect of SLC38A2 on cell proliferation was investigated by colony formation. RESULTS: Circ_001859 was lowly expressed in pancreatic cancer tissues and cells. In vitro assays showed that overexpression of circ_001859 could inhibit the proliferation, migration and invasion of pancreatic cancer. In addition, this effect was also confirmed in xenograft transplantation model. Circ_001859 could be bind to miR-21-5p and sponge its expression in pancreatic cancer cells. Overexpression of miR-21-5p enhanced the proliferation, migration and invasion ability of pancreatic cancer cells, while the inhibition of miR-21-5p expression suppressed these abilities. Moreover, miR-21-5p directly targeted at SLC38A2 and inhibited SLC38A2 expression levels while circ_001859 up-regulated SLC38A2 levels. SLC38A2 expression knockdown enhanced cell proliferation but SLC38A2 overexpression resulted in decreased proliferation, and effects of SLC38A2 could be rescued by miR-21-5p and circ_001859. In addition, both QRT-PCR and immunofluorescence confirmed that circ_001859 could regulate tumor epithelial-mesenchymal transition (EMT) through the miR-21-5p/SLC38A2 pathway. CONCLUSIONS: This study suggests that circ_001859 may inhibit the proliferation, invasion and EMT of pancreatic cancer through the miR-21-5p/SLC38A2 pathway. Show more

Keywords: Pancreatic cancer, circ_001859, miR-21-5p, SLC38A2

DOI: 10.3233/CBM-220229

Citation: Cancer Biomarkers, vol. 37, no. 1, pp. 39-52, 2023

Authors: Chen, Yupeng | Wu, Yuanyuan

Article Type: Research Article

Abstract: BACKGROUND: Lung adenocarcinoma (LUAD) has a high incidence and poor prognosis, and multiple circRNAs (circRNAs) have been found to regulate LUAD. OBJECTIVE: This study focuses on the effect and mechanism of hsa_circ_0070661 in LUAD. METHODS: LUAD tissues and para-cancerous tissues were collected from 38 patients diagnosed with LUAD in our hospital. Hsa_circ_0070661, miR-556-5p and TEK Receptor Tyrosine Kinase (TEK) levels were evaluated using western blotting and RT-qPCR, and the targeting relationship was detected by luciferase reporter and RIP assays. Cell migration, viability, apoptosis-related proteins, (Bcl-2 and Bax) and tumor growth in vivo …were assessed by Transwell, CCK-8, western blotting and xenograft assays, respectively. RESULTS: Results indicated downregulation of hsa_circ_0070661 and TEK in LUAD cell lines and tissues, whereas upregulation of miR-556-5p. Hsa_circ_0070661 upregulation restrained the viability, migration and tumor growth of LUAD cells, and promoted apoptosis. Hsa_circ_0070661 could directly target miR-556-5p to upregulate TEK expression in LUAD. MiR-556-5p upregulation promoted the malignant phenotypes of LUAD cells and reversed the anti-cancer effect of hsa_circ_0070661 overexpression, while TEK upregulation inhibited LUAD progression and somewhat eradicated the cancer-promoting effect of miR-556-5p upregulation. CONCLUSIONS: Hsa_circ_0070661 sponges miR-556-5p to inhibit LUAD development via regulating TEK, providing a promising molecular target for LUAD clinical therapy. Show more

Keywords: Hsa_circ_0070661, miR-556-5p, TEK, lung adenocarcinoma

DOI: 10.3233/CBM-220282

Citation: Cancer Biomarkers, vol. 37, no. 1, pp. 53-66, 2023