Cancer Biomarkers - Volume 27, issue 2

Authors: Ritter, Andrea | Hirschfeld, Marc | Berner, Kai | Jaeger, Markus | Grundner-Culemann, Franziska | Schlosser, Pascal | Asberger, Jasmin | Weiss, Daniela | Noethling, Claudia | Mayer, Sebastian | Erbes, Thalia

Article Type: Research Article

Abstract: BACKGROUND: Deregulated microRNAs (miRNAs) in breast and gynecological cancer might contribute to improve early detection of female malignancies. OBJECTIVE: Specification of miRNA types in serum and urine as minimally-invasive biomarkers for breast (BC), endometrial (EC) and ovarian cancer (OC). METHODS: In a discovery phase, serum and urine samples from 17 BC, five EC and five OC patients vs. ten healthy controls (CTRL) were analyzed with Agilent human miRNA microarray chip. Selected miRNA types were further investigated by RT-qPCR in serum (31 BC, 13 EC, 15 OC patients, 32 CTRL) and urine (25 BC, …10 EC, 10 OC patients, 30 CTRL) applying two-sample t-tests. RESULTS: Several miRNA biomarker candidates exhibited diagnostic features due to distinctive expression levels (serum: 26; urine: 22). Among these, miR-518b, -4719 and -6757-3p were found specifically deregulated in BC serum. Four, non-entity-specific, novel biomarker candidates with unknown functional roles were identified in urine (miR-3973; -4426; -5089-5p and -6841). RT-qPCR identified miR-484/-23a (all p ⩽ 0.001) in serum as potential diagnostic markers for EC and OC while miR-23a may also serve as an endogenous control in BC diagnosis. CONCLUSIONS: Promising miRNAs as liquid biopsy-based tools in the detection of BC, EC and OC qualified for external validation in larger cohorts. Show more

Keywords: miR-484, miR-23a-3p, liquid biopsy, miRNA, endometrial cancer, ovarian cancer, breast cancer, screening

DOI: 10.3233/CBM-190575

Citation: Cancer Biomarkers, vol. 27, no. 2, pp. 225-242, 2020

Authors: Xiong, Yanlu | Feng, Yangbo | Qiao, Tianyun | Han, Yong

Article Type: Research Article

Abstract: BACKGROUND: Prognostic biomarkers are promising targets for cancer prevention and treatment. OBJECTIVE: We try to filtrate survival-related genes for non-small cell lung cancer (NSCLC) via transcriptome analysis. METHODS: Transcriptome data and clinical information of Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), mainly subtypes of NSCLC, were obtained from The Cancer Genome Atlas (TCGA) program. Differentially expressed genes (DEGs) analyzed by DESeq2 package were regarded as candidate genes. For survival analysis, univariate and multivariate Cox regression were applied to select biomarkers for overall survival (OS) and progression-free survival (PFS), where univariate analysis was for …preliminary filtration and multivariate analysis considering age, gender, TNM parameters and clinical stage was for ultimate determination. Gene ontology (GO) analysis and pathway enrichment were used for biological annotation. RESULTS: We ultimately acquired a series of genes closely related to prognosis. For LUAD, we determined 314 OS-related genes and 275 PFS-related genes, while 54 OS-related genes and 78 PFS-related genes were chosen for LUSC. The final biological analysis indicated important function of proliferative signaling in LUAD but for LUSC, only cornification process had statistical meaning. CONCLUSIONS: We strictly determined prognostic genes of NSCLC, which would contribute to its carcinogenesis investigation and therapeutic methods improvement. Show more

Keywords: Lung adenocarcinoma, lung squamous cell carcinoma, transcriptome, prognosis, biomarker

DOI: 10.3233/CBM-190222

Citation: Cancer Biomarkers, vol. 27, no. 2, pp. 243-250, 2020

Authors: Abdelrahman, Aziza E. | Ibrahim, Doaa Abdelaziz | El-Azony, Ahmed | Alnagar, Ahmed A. | Ibrahim, Amr

Article Type: Research Article

Abstract: BACKGROUND: The recognition of high-risk colon cancer patients prone to chemoresistant and recurrent disease is a challenge. OBJECTIVES: We aimed to assess the immunohistochemical expression of ERCC1, PARP-1, and AQP1 in 60 cases of stage II and III colon cancer who underwent curative resection and adjuvant chemotherapy. Their predictive role of tumor progression and disease-free survival (DFS) was analyzed. METHODS: The immunohistochemical expression of ERCC1, PARP-1, and AQP1 in 60 cases of stage II and III colon cancer who underwent curative resection and adjuvant chemotherapy was studied. The collected data on the overall …survival (OS), disease-free survival (DFS), and the response to the chemotherapy were analyzed. RESULTS: Positive nuclear ERCC1 expression was identified in 58.3% of the patients, ERCC1 expression was significantly associated with left-sided tumors (P < 0.01). Moreover, its expression was significantly associated with the aggressive tumor characteristics including high grade, lymph node metastasis and advanced tumor stage (P < 0.001 for each). High nuclear PARP-1 expression was observed in 63.3% of the cases, and its expression was significantly associated with tumor grade and lymph node metastasis (P = 0.003 for each). Positive membranous AQP1 expression was identified in 41.7% of patients, and it was associated with high grade, lymph node metastasis and advanced tumor stage (P < 0.001 for each). During the follow-up period, 23 patients (38.3%) exhibited a tumor progression; this was significantly associated with positive ERCC1, high PARP-1, and negative AQP1 expression. Statistics of the survival data revealed that shorter DFS was significantly associated with positive ERCC1, high PARP-1, and positive AQP1 expression (P = 0.005, 0.016, 0.002, respectively). CONCLUSIONS: ERCC1, PARP1, and AQP1 are adverse prognostic biomarkers in stage II–III colon cancer. Moreover, adjuvant chemotherapy may not be beneficial for patients with positive ERCC1, high PARP1, and AQP1-negative tumors. Therefore, we recommend that ERCC1, PARP-1, and AQP1 should be assessed during the selection of the treatment strategy for stage II–III colon cancer patients. Show more

Keywords: Colon cancer, ERCC1, PARP-1, AQP1, immunohistochemistry

DOI: 10.3233/CBM-190994

Citation: Cancer Biomarkers, vol. 27, no. 2, pp. 251-264, 2020

Authors: Gu, Yong-yao | Chen, Gang | Lin, Peng | Cheng, Ji-wen | Huang, Zhi-guang | Luo, Jie | Zhai, Gao-qiang | Wang, Ying-lun | Yan, Hai-biao | Li, Sheng-hua

Article Type: Research Article

Abstract: BACKGROUND: Tumor-infiltrating immune cells are indispensable to the progression and prognosis of clear cell renal cell carcinoma (ccRCC). OBJECTIVE: The aim of this study was to explore the clinical implications of immune cell infiltrates in ccRCC. METHODS: The Cancer Genome Atlas (TCGA) database (N = 515) and E-MTAB-1980 cohort of patients (N = 101) were adopted to estimate the prognostic value of immune cell infiltration. Twenty-four types of immune cells were evaluated using single-sample gene set enrichment analysis. Cox regression analyses were conducted …to develop an immune risk score. RESULTS: Survival analyses revealed that 13 genes significantly associated with the overall survival (OS). Furthermore, multivariate Cox analysis identified an immune risk score on the basis of mast cells, natural killer CD56bright cells, T helper 17 (Th17) cells, and Th2 cells. The immune risk score was associated with OS, with hazard ratios of 2.72 (95% CI 2.17–3.40) and 3.24 (95% CI 1.64–6.44) in TCGA and E-MTAB-1980 datasets, respectively. This immune risk score was significantly correlated with some immunotherapy-related biomarkers. CONCLUSIONS: We profiled a prognostic signature and established an immune risk score model for ccRCC, which could provide novel predictive markers for patients with ccRCC and an indicator for immunotherapy response measurement. Show more

Keywords: Clear cell renal cell carcinoma, tumor-infiltrating immune cells, prognosis, RNA-sequencing

DOI: 10.3233/CBM-191017

Citation: Cancer Biomarkers, vol. 27, no. 2, pp. 265-275, 2020

Authors: Liao, Chan | Shen, Di-Ying | Xu, Xiao-Jun | Song, Hua | Xu, Wei-Qun | Zhao, Fen-Ying | Yang, Shi-Long | Tang, Yong-Min

Article Type: Research Article

Abstract: BACKGROUND: Prognostic factors are not well exploited in childhood T-cell acute lymphoblastic leukemia (T-ALL). OBJECTIVE: The aim of this study was to analyze the prognostic role of CD38 as well as minimal residual disease (MRD) and other biological factors in T-ALL. METHODS: Immunophenotyping of bone marrow (BM) at diagnosis and MRD levels were determined using a standard panel of antibodies by 4-colour flow cytometry. A total of 96 children with T-ALL were enrolled. RESULTS: The results showed that 97.9% of T-ALL patients were positive for CD38 with a median level …of 85.3%. CD38-high group had a worse early treatment response than the CD38-low group. However, CD38 levels were not associated with prognosis, albeit CD38-high group had a worse 5-year event free survival rate (55.1% vs. 66.6%, P > 0.05) and a higher 5-year cumulative incidence of relapse (35.6% vs. 19.8%, P > 0.05). Very high MRD levels (> 10%) were related to the worse survival. Neither flow cytometry based minimal residual disease (MRD) levels nor CD38 expression levels showed significant relation to the hazard of relapse (P > 0.05). CONCLUSIONS: We conclude that T-ALL has a high level of CD38 expression which is not associated with prognosis. Very high MRD level (> 10%) is related to the worse survival, however, FCM based MRD detection does not convey a significant prognostic value. Show more

Keywords: CD38, T-ALL, childhood, survival, relapse

DOI: 10.3233/CBM-190946

Citation: Cancer Biomarkers, vol. 27, no. 2, pp. 277-284, 2020