Cancer Biomarkers - Volume 24, issue 3

Authors: Krawczyk, Malgorzata A. | Karpinsky, Gabrielle | Izycka-Swieszewska, Ewa | Gabrych, Anna | Kunc, Michal | Fatyga, Aleksandra | Garstka, Monika | Styczewska, Malgorzata | Sokolewicz, Ewa M. | Szlagatys-Sidorkiewicz, Agnieszka | Kazanowska, Bernarda | Bien, Ewa

Article Type: Research Article

Abstract: BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is rare, aggressive soft tissue sarcoma which may affect children. OBJECTIVE: We aimed to assess prognostic significance of immunohistochemical (IHC) markers, osteopontin, fibronectin, survivin, cyclin D1 and p53, in pediatric MPNST. METHODS: A total of 26 pediatric MPNST patients were enrolled in the current study with a median follow-up of 51 months. IHC staining using commercially available monoclonal antibodies were employed to detect analyzed antigens on tissue microarrays. Eventually, all markers were subclassified to high (H) and low (L) expression categories in all analyzed tumors. …RESULTS: High IHC expressions of survivin, cyclin D1, osteopontin, fibronectin, and p53 were detected in 18 (69.2%), 13 (50%), 16 (61.5%), 16 (61.5%), and 13 (50%) tumors, respectively. A significant correlation was demonstrated between cyclin D1 and osteopontin (p = 0.004). Both markers were associated with neurofibromatosis type 1 (NF1) status (p = 0.041 and p = 0.037, respectively). H-fibronectin was more prevalent in deeply located tumors (p = 0.046). None of the markers was associated with IRS stage, age at diagnosis, and tumor size. Univariate analysis identified IRS stage, regional lymph node metastases, NF1, and cyclin D1 as variables associated with overall survival (OS), whereas tumor depth, osteopontin, and cyclin D1 – for relapse-free survival (RFS). Subsequent multivariate analysis identified cyclin D1 and p53 as independent variables predicting RFS, whereas cyclin D1 and regional lymph nodes status were independent predictors for OS. Show more

DOI: 10.3233/CBM-181572

Citation: Cancer Biomarkers, vol. 24, no. 3, pp. 351-361, 2019

Authors: Zou, Shitao | Xu, Yan | Chen, Xingxing | He, Chao | Gao, Aidi | Zhou, Jundong | Chen, Yihong

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: Dysregulation of DNA polymerase iota (Pol ι ) in breast cancer might contribute to the accumulation of genomic mutations and promotes breast cancer progression. In this study we explored the clinical relevance and biological function of Pol ι in breast cancer. METHODS: qRT-PCR was used to determine the expression levels of Pol ι in 31 breast cancer tissues. Then the stable overexpression of Pol ι and knockdown of Pol ι breast cancer cell lines were constructed. Wound-healing assay and …transwell assay were performed to evaluate cell migratory and invasiveness, respectively. Signaling pathway was analyzed by western blot. RESULTS: The expression levels of Pol ι is overexpressed in breast cancer tissues and significantly higher in breast cancer tissues with lymph node metastasis compared to those without lymph node metastasis. Elevated Pol ι expression promoted migratory and invasiveness of breast cancer cells. Signaling pathway analysis indicated EGFR-ERK cascade works as a mediator of Pol ι -induced EMT of breast cancer cells. CONCLUSIONS: These data demonstrate the underlying mechanism by which Pol ι promotes breast cancer progression, suggesting that Pol ι may be a potential therapeutic target against breast cancer. Show more

Keywords: Breast cancer, Pol ι, metastasis, EMT, EGFR

DOI: 10.3233/CBM-181516

Citation: Cancer Biomarkers, vol. 24, no. 3, pp. 363-370, 2019

Authors: Bai, Yuquan | Xiong, Lecai | Zhu, Minglin | Yang, Zetian | Zhao, Jinping | Tang, Hexiao

Article Type: Research Article

Abstract: Lung cancer is a malignant tumor with high morbidity and mortality, of which 80% is non-small cell lung cancer (NSCLC). And lung adenocarcinoma (LUAD) is the most important and common subtype in the NSCLC. In current study, the microarray data GSE31210 containing LUAD (n = 226) and normal lung tissue (n = 20) was analyzed to identify 965 differentially expressed genes, on which weighted gene co-expression network analysis was performed. Finally, it was confirmed that there was a significant correlation between brown module and LUAD stage. In the significant module, …a total of 54 network hub genes were identified, and six of them were also identified as hub genes of the protein-protein interaction network. In validation, KIF2C showed a higher correlation with disease stage than other hub genes (p < 0.001, R2 = 0.955). Functional enrichment suggests that KIF2C is associated with cell mitosis and cell cycle. Combined with clinicopathological parameters, we found that the high expression of KIF2C is closely related to the relapse and tumor stage of LUAD. Survival analysis showed a significant reduction in overall survival in LUAD patients with high expression of KIF2C. Gene set enrichment analysis (GSEA) also showed that the “cell cycle signaling pathway” and “P53 related pathway” were significantly enriched in LUAD samples with high expression of KIF2C (FDR < 0.05). In conclusion, based on the co-expression analysis, KIF2C was identified in the association with progression and prognosis of LUAD, which might refer a poor prognosis probably by regulating cell cycle signaling pathway. Show more

Keywords: KIF2C, Lung adenocarcinoma, co-expression analysis, cell cycle

DOI: 10.3233/CBM-181512

Citation: Cancer Biomarkers, vol. 24, no. 3, pp. 371-382, 2019