Cancer Biomarkers - Volume 39, issue 1

Authors: Zhu, Kongjun | Yi, Cen | Tong, Chuanming

Article Type: Research Article

Abstract: OBJECTIVE: Accumulating evidence indicates that circular RNAs (circRNAs) contribute to breast cancer (BC) development and progression. However, the role of circ_0058063 in BC and its underlying molecular processes remain unclear. METHODS: The expression of circ_0058063, miR-557, and DLGAP5 in BC tissues and cells was determined using real time quantitative PCR or western blotting. The functions of circ_0058063 in BC cells were detected using CCK-8, Transwell, caspase-3 activity, and xenograft tumor assays. The specific binding of circ_0058063/miR-557 and DLGAP5/miR-557 was verified using RNA immunoprecipitation (RIP) and dual-luciferase reporter assays. RESULTS: circ_0058063 expression was upregulated …in BC tissues and cells. circ_0058063 knockdown inhibited proliferation and migration but promoted apoptosis in MCF-7 and MDA-MB-231 cells in vitro . In vivo studies further validated that the knockdown of circ_0058063 repressed tumor growth. Mechanistically, circ_0058063 directly sponged miR-557 and negatively regulated its expression. Additionally, miR-557 inhibition reversed the tumor-suppressive effects of the circ_0058063 knockdown on the survival of MDA-MB-231 and MCF-7 cells. Moreover, miR-557 directly targeted DLGAP5. DLGAP5 knockdown suppressed MCF-7 and MDA-MB-231 cell growth, and these effects were reversed by miR-557 downregulation. CONCLUSION: Our findings verify that circ_0058063 acts as a sponge for miR-557 to upregulate DLGAP5 expression. These findings suggest that the circ_0058063/miR-557/DLGAP5 axis is an important regulator of oncogenic function and may be a promising therapeutic target for BC. Show more

Keywords: circ_0058063, miR-557, DLGAP5, breast cancer

DOI: 10.3233/CBM-220410

Citation: Cancer Biomarkers, vol. 39, no. 1, pp. 1-13, 2024

Authors: Huang, Wei | Wei, Suosu | Dong, Xiaofeng | Tang, Yuntian | Tang, Yi | Liu, Hongjun | Huang, Junzhang | Yang, Jianrong

Article Type: Research Article

Abstract: BACKGROUND: The correlation between the preoperative albuminalkaline phosphatase ratio (AAPR) and the prognosis of hepatocellular carcinoma (HCC) patients after radical resection is still not comprehensive. OBJECTIVE: This study aims to observe the correlation between preoperative AAPR and the prognosis of HCC patients after radical resection. METHODS: We constructed a retrospective cohort study and included 656 HCC patients who underwent radical resection. The patients were grouped after determining an optimum AAPR cut-off value. We used the Cox proportional regression model to assess the correlation between preoperative AAPR and the prognosis of HCC patients after radical …resection. RESULTS: The optimal cut-off value of AAPR for assessing the prognosis of HCC patients after radical resection was 0.52 which was acquired by using X-tile software. Kaplan-Meier analysis curves showed that a low AAPR (⩽ 0.52) had a significantly lower rate of overall survival (OS) and recurrence-free survival (RFS) (P < 0.05). Multiple Cox proportional regression showed that an AAPR > 0.52 was a protective factor for OS (HR = 0.66, 95%CI 0.45-0.97, p = 0.036) and RFS (HR = 0.70, 95% CI 0.53–0.92, p = 0.011). CONCLUSIONS: The preoperative AAPR level was related to the prognosis of HCC patients after radical resection and can be used as a routine preoperative test, which is important for early detection of high-risk patients and taking personalized adjuvant treatment. Show more

Keywords: Albumin-alkaline phosphatase ratio, survival rates, surgery, hepatocellular carcinoma, prognosis

DOI: 10.3233/CBM-230108

Citation: Cancer Biomarkers, vol. 39, no. 1, pp. 15-26, 2024

Authors: Hou, Qing | Li, He | Liang, Yu | Yao, Ningning | Cao, Xin | Liu, Jianting | Sun, Bochen | Feng, Peixin | Zhang, Wenjuan | Cao, Jianzhong

Article Type: Research Article

Abstract: BACKGROUND: At present, peripheral blood markers are easily accessible information and clinically valuable prognostic indicators in extranodal nasal-type natural killer/T-cell lymphoma (ENKTCL). Nevertheless, the role of its comprehensive score in ENKTCL remains to be determined. OBJECTIVE: Therefore, this study aimed to investigate the prognostic effect of the peripheral inflammation score on ENKTCL. METHODS: The retrospective study included 183 patients with ENKTCL. Univariate Cox regression analyses and least absolute shrinkage and selection operator (LASSO) Cox regression were used to construct the inflammation-related prognostic index named Risk. Univariate and multivariate Cox regression analyses and regression …adjustment with propensity score matching (PSM) were used to evaluate the prognostic ability of risk. The performance of the modified nomogram-revised risk index (NRI) by integrating risk was evaluated with the area under the time-dependent receiver operating characteristic (ROC) curve (AUC), decision curve analysis (DCA), and integrated Brier score (IBS). RESULTS: The risk cut-off value, constructed by the lymphocyte count, platelet count, albumin level, LMR, and PNI, was - 1.3486. Before PSM, multivariate analysis showed that risk was significantly associated with OS (HR = 2.577, 95% CI = 1.614–4.114, P < 0.001) and PFS (HR = 2.679, 95% CI = 1.744–4.114, P < 0.001). After PSM adjustment, risk was still an independent factor for OS (HR = 2.829, 95% CI = 1.601–5.001, P < 0.001) and PFS (HR = 2.877, 95% CI = 1.735–4.770, P < 0.001). With the NRI, the modified NRI by integrating risk increased the AUC and clinical net benefit and decreased the IBS. CONCLUSIONS: Risk is an easily accessible and inexpensive indicator that may be used as a prognostic marker and could improve NRI predictive power in patients with ENKTCL. Show more

Keywords: Extranodal NK-T-Cell lymphoma, nasal type, biomarker, inflammations, survival

DOI: 10.3233/CBM-230067

Citation: Cancer Biomarkers, vol. 39, no. 1, pp. 27-36, 2024

Authors: Wen, Diguang | Wang, Shuling | Yu, Jiajian | Yu, Ting | Liu, Zuojin | Li, Yue

Article Type: Research Article

Abstract: BACKGROUND: Increasing evidence has indicated that abnormal methionine metabolic activity and tumour-associated macrophage infiltration are correlated with hepatocarcinogenesis. However, the relationship between methionine metabolic activity and tumour-associated macrophage infiltration is unclear in hepatocellular carcinoma, and it contributes to the occurrence and clinical outcome of hepatocellular carcinoma (HCC). Thus, we systematically analysed the expression patterns of methionine metabolism and macrophage infiltration in hepatocellular carcinoma using bioinformatics and machine learning methods and constructed novel diagnostic and prognostic models of HCC. METHODS: In this study, we first mined the four largest HCC mRNA microarray datasets with patient clinical data …in the GEO database, including 880 tissue mRNA expression datasets. Using GSVA analysis and the CIBERSORT and EPIC algorithms, we quantified the methionine metabolic activity and macrophage infiltration degree of each sample. WGCNA was used to identify the gene modules most related to methionine metabolism and tumour-associated macrophage infiltration in HCC. The KNN algorithm was used to cluster gene expression patterns in HCC. Random forest, logistic regression, Cox regression analysis and other algorithms were used to construct the diagnosis and prognosis model of HCC. The above bioinformatics analysis results were also verified by independent datasets (TCGA-LIHC, ICGC-JP and CPTAC datasets) and immunohistochemical fluorescence based on our external HCC panel. Furthermore, we carried out pancancer analysis to verify the specificity of the above model and screened a wide range of drug candidates. RESULTS: We identified two methionine metabolism and macrophage infiltration expression patterns, and their prognoses were different in hepatocellular carcinoma. We constructed novel diagnostic and prognostic models of hepatocellular carcinoma with good diagnostic efficacy and differentiation ability. CONCLUSIONS: Methionine metabolism is closely related to tumour-associated macrophage infiltration in hepatocellular carcinoma and can help in the clinical diagnosis and prognosis of HCC. Show more

Keywords: HCC, macrophages, immune microenvironment, bioinformatics, methionine metabolism, machine learning

DOI: 10.3233/CBM-220421

Citation: Cancer Biomarkers, vol. 39, no. 1, pp. 37-48, 2024

Authors: Lin, Tingru | Guo, Jingzhu | Peng, Yifan | Li, Mei | Liu, Yulan | Yu, Xin | Wu, Na | Yu, Weidong

Article Type: Research Article

Abstract: BACKGROUND: Abelson interactor 1 (ABI1) is associated with the metastasis and prognosis of many malignancies. The association between ABI1 transcript spliced variants, their molecular constitutive exons and exon–exon junctions (EEJs) in 14 cancer types and clinical outcomes remains unsolved. OBJECTIVE: To identify novel cancer metastatic and prognostic biomarkers from ABI1 total mRNA, TSVs, and molecular constitutive elements. METHODS: Using data from TCGA and TSVdb database, the standard median of ABI1 total mRNA, TSV, exon, and EEJ expression was used as a cut-off value. Kaplan-Meier analysis, Chi-squared test (X 2 ) …and Kendall’s tau statistic were used to identify novel metastatic and prognostic biomarkers, and Cox regression analysis was performed to screen and identify independent prognostic factors. RESULTS: A total of 35 ABI1-related factors were found to be closely related to the prognosis of eight candidate cancer types. A total of 14 ABI1 TSVs and molecular constitutive elements were identified as novel metastatic and prognostic biomarkers in four cancer types. A total of 13 ABI1 molecular constitutive elements were identified as independent prognostic biomarkers in six cancer types. CONCLUSIONS: In this study, we identified 14 ABI1-related novel metastatic and prognostic markers and 21 independent prognostic factors in total 8 candidate cancer types. Show more

Keywords: ABI1 transcript variant, molecular constitutive element, metastasis, prognosis, cancer biomarker

DOI: 10.3233/CBM-220348

Citation: Cancer Biomarkers, vol. 39, no. 1, pp. 49-62, 2024

Authors: He, Peina | Liu, Zhi | Qi, Jinxu | Shan, Junrao | Sheng, Jianyun

Article Type: Research Article

Abstract: BACKGROUND: LINC00885 is a novel oncogenic long noncoding RNA (LncRNA) which is upregulated in various types of cancer, but its function in triple-negative breast cancer (TNBC) remains unknown. OBJECTIVE: This study aimed to determine the role of LINC00885 on TNBC development. METHODS: Clinical interrelation and survival analysis were determined using online database. The CCK-8 and Transwell assays were used to detect the proliferation and migration behaviors in TNBC cell lines. The interaction among genes was detected by RNA pull down assay. RESULTS: LncRNA LINC00885 was highly expressed in TNBC compared …to normal breast like. Low levels of LINC00885 was related to good prognosis in TNBC patients compared to TNBC patients with high LINC00885. LINC00885-downregulation inhibited, whereas LINC00885-overexpression promoted the proliferation and migration capability of TNBC cell lines. In TNBC cell lines, noncatalytic region of tyrosine kinase 1 (NCK1) expression was positively associated with LINC00885 expression, and shRNA-mediated the depletion of NCK1 significantly abolished LINC00885 upregulation-mediated pro-tumor effects. Combined with online databases, miR-654-3p was screened as the direct target gene of LINC00885, which could directly bind to 3’-untranslated regions (3‘-UTR) of NCK1, resulting in the decreased expression of NCK1 in TNBC cell lines. LINC00885 overexpression-mediated the upregulation of NCK1 was abrogated by miR-654-3p mimics. MiR-654-3p mimics significantly rescued the tumor promotive role caused by LINC00885-overexpression. However, exogenous NCK1 notably eliminated the anti-tumor effects caused by miR-654-3p mimics in LINC00885-overexpressed cells. CONCLUSIONS: LINC00885 is expressed at a high level in TNBC. LINC00885 promoted proliferation and migration by regulating the miR-654-3p/NCK1 axis in TNBC cell lines. Possibly, LINC00885 can be served as a potential therapeutic target for TNBC. Show more

Keywords: Long noncoding RNA LINC00885, triple-negative breast cancer, noncatalytic region of tyrosine kinase 1, miR-654-3p

DOI: 10.3233/CBM-230143

Citation: Cancer Biomarkers, vol. 39, no. 1, pp. 63-78, 2024