Cancer Biomarkers - Volume 32, issue 3

Authors: Fan, Caibin | Lu, Wei | Li, Kai | Zhao, Chunchun | Wang, Fei | Ding, Guanxiong | Wang, Jianqing

Article Type: Research Article

Abstract: BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) is the lethal stage of prostate cancer and the main cause of morbidity and mortality, which is also a potential target for immunotherapy. METHOD: In this study, using the Approximate Relative Subset of RNA Transcripts (CIBERSORT) online method, we analysed the immune cell abundance ratio of each sample in the mCRPC dataset. The EdgeR (an R package) was used to classify differentially expressed genes (DEGs). Using the Database for annotation, visualisation and interactive exploration (DAVID) online method, we performed functional enrichment analyses. STRING online database and Cytoscape tools have been …used to analyse protein-protein interaction (PPI) and classify hub genes. RESULTS: The profiles of immune infiltration in mCRPC showed that Macrophages M2, Macrophages M0, T cells CD4 memory resting, T cells CD8 and Plasma cells were the main infiltration cell types in mCRPC samples. Macrophage M0 and T cell CD4 memory resting abundance ratios were correlated with clinical outcomes. We identified 1102 differentially expressed genes (DEGs) associated with the above two immune cells to further explore the underlying mechanisms. Enrichment analysis found that DEGs were substantially enriched in immune response, cell metastasis, and metabolism related categories. We identified 20 hub genes by the protein-protein interaction network analysis. Further analysis showed that three critical hub genes, CCR5, COL1A1 and CXCR3, were significantly associated with prostate cancer prognosis. CONCLUSION: Our findings revealed the pattern of immune cell infiltration in mCRPC, and identified the types and genes of immune cells correlated with clinical outcomes. A new theoretical basis for immunotherapy may be given by our results. Show more

Keywords: Immune infiltration, metastatic castration resistant prostate cancer (mCRPC), RNA sequencing, bioinformatics analysis, immunotherapy

DOI: 10.3233/CBM-203222

Citation: Cancer Biomarkers, vol. 32, no. 3, pp. 363-377, 2021

Authors: Ebian, Huda F. | Elshorbagy, Sherin | Mohamed, Haitham | Embaby, Ahmad | Khamis, Tarek | Sameh, Reham | Sabbah, Norhan A. | Hussein, Samia

Article Type: Research Article

Abstract: BACKGROUND: Both Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD ) and Additional Sex Comb-like 1 (ASXL1) mutations are frequent and early genetic alteration events in acute myeloid leukemia (AML) patients. These genetic alterations may be associated with an unfavorable prognosis. OBJECTIVE: Up to our knowledge, this is the first study performed to evaluate the clinical implication and prognostic significance of FLT3-ITD and ASXL1 mutations and their coexistence on the outcome of Egyptian AML patients. METHODS: Our study included 83 patients with AML who were subjected to immunophenotyping and detection …of FLT3-ITD and ASXL1 gene mutation by polymerase chain reaction (PCR) and real-time PCR, respectively. RESULTS: FLT3-ITD and ASXL1 mutations were detected in 20.5% and 18.1% of AML patients respectively. Seven patients (8.4%) had co-expression of both genes’ mutations. FLT3-ITD mutation was significantly higher in younger age, higher WBCs count and poor cytogenetic risk patients (P = 0.01, < 0.001 and 0.008 respectively). ASXL1 mutation was significantly higher in intermediate cytogenetic risk patients (P = 0.2). The mean period of survival and relapse-free survival (RFS) were significantly reduced in FLT3-ITD and ASXL1 mutations compared with their non-mutant types (P = 0.01 and 0.03 respectively). Both mutations were independent risk factors for overall survival (OS) and (RFS) in univariate and multivariate analysis in AML patients. CONCLUSION: FLT3-ITD and ASXL1 gene mutations or their coexistence can predict a poor prognosis in AML patients. Show more

Keywords: Acute myeloid leukemia, FLT3-ITD mutation, ASXL1 mutation, overall survival, prognosis

DOI: 10.3233/CBM-210024

Citation: Cancer Biomarkers, vol. 32, no. 3, pp. 379-389, 2021

Authors: Li, Weibo | Song, Yizuo | Pan, Chunyu | Yu, Junhui | Zhang, Jianan | Zhu, Xueqiong

Article Type: Research Article

Abstract: BACKGROUND: Role of aquaporin-8 (AQP8) in cervical cancer has not been fully elucidated. OBJECTIVE: We aim to explore the impacts of AQP8 on viability, apoptosis and metastasis in cervical cancer cells. METHODS: AQP8 protein expression in cervical carcinoma specimens and cell lines was detected by IHC and western blot analysis. Lentivirus-mediated transfection was used to upregulate and knockdown AQP8 in cells. Cell viability and apoptosis were assessed by CCK-8 and flow cytometry assays, respectively. Transwell experiments were conducted to investigate cell invasive and migratory capabilities. EMT-related markers were detected by western blot analysis. …RESULTS: A strong positive of AQP8 protein expression was observed in cervical cancer tissues. Western blot analysis confirmed overexpression and knockdown of AQP8 in SiHa cells. AQP8-overexpressed SiHa cells displayed an enhanced viability, reduced apoptotic rate, increased invasive and migratory abilities. Knockdown of AQP8 inhibited the viability, promoted the apoptosis, and suppressed invasion and migration. Furthermore, AQP8 overexpression significantly upregulated vimentin and N-cadherin, and downregulated E-cadherin, which were reversed by AQP8 knockdown. CONCLUSIONS: AQP8 increases viability, inhibits apoptosis, and facilitates metastasis in SiHa cells. This may be associated with EMT-related markers regulated by AQP8. AQP8 could serve as a potential marker for cervical cancer progression. Show more

Keywords: Aquaporins, AQP8, cervical cancer, invasion, migration, EMT

DOI: 10.3233/CBM-203251

Citation: Cancer Biomarkers, vol. 32, no. 3, pp. 391-400, 2021

Authors: Ouyang, Renren | Wu, Shiji | Zhang, Bo | Wang, Ting | Yin, Botao | Huang, Jin | Wei, Wei | Huang, Min | Zhang, Minxia | Wang, Yun | Wang, Feng | Hou, Hongyan

Article Type: Research Article

Abstract: BACKGROUND: This study aimed to investigate the efficiency of combining tumor-associated antigens (TAAs) and autoantibodies in the diagnosis of lung cancer. METHODS: The serum levels of TAAs and seven autoantibodies (7-AABs) were detected from patients with lung cancer, benign lung disease and healthy controls. The performance of a new panel by combing TAAs and 7-AABs was evaluated for the early diagnosis of lung cancer. RESULTS: The positive rate of 7-AABs was higher than the single detection of antibody. The positive rate of the combined detection of 7-AABs in lung cancer group (30.2%) was …significantly higher than that of healthy controls (16.8%), but had no statistical difference compared with that of benign lung disease group (20.8%). The positive rate of 7-AABs showed a tendency to increase in lung cancer patients with higher tumor-node-metastasis (TNM) stages. For the pathological subtype analysis, the positive rate of 7-AABs was higher in patients with squamous cell carcinoma and small cell lung cancer than that of adenocarcinoma. The levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment 211 (CYFRA 21-1) were significantly higher than that of benign lung disease and healthy control groups. An optimal model was established (including 7-AABs, CEA and CYFRA21-1) to distinguish lung cancer from control groups. The performance of this model was superior than that of single markers, with a sensitivity of 52.26% and specificity of 77.46% in the training group. Further assessment was studied in another validation group, with a sensitivity of 44.02% and specificity of 83%. CONCLUSIONS: The diagnostic performance was enhanced by combining 7-AABs, CEA and CYFRA21-1, which has critical value for the screening and early detection of lung cancer. Show more

Keywords: Lung cancer, tumor-associated antigen, tumor-associated autoantibodies, CEA, CYFRA 21-1

DOI: 10.3233/CBM-210099

Citation: Cancer Biomarkers, vol. 32, no. 3, pp. 401-409, 2021