scholarly journals Diagnostic and Prognostic Potential of Circulating and Tissue BATF2 in Nasopharyngeal Carcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhaolei Cui ◽  
Yingying Lin ◽  
Dan Hu ◽  
Jing Wu ◽  
Wei Peng ◽  
...  

Background: Current biomarkers for nasopharyngeal carcinoma (NPC) are less effective for early diagnosis and prognosis. The basic leucine zipper ATF-like transcription factor 2 (BATF2) gene has been shown to have a tight association with the pathogenesis of various malignancies but received scant attention in NPC research. We aimed to assess the performances of circulating and tissue BATF2 in the diagnosis and prognosis of NPC.Materials and Methods: Immunohistochemistry (IHC) microarrays were performed to quantitate the BATF2 protein expression in NPC tissues. The relationships of BATF2 protein expression with clinicopathological characteristics and NPC prognosis were assessed. BATF2 mRNA expressions in serum and serum-derived exosomes were determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay.Results: The IHC microarrays revealed a predominant nuclear expression of BATF2 in NPC cells. The Kaplan-Meier survival analysis showed that BATF2-positive NPC patients enjoyed longer overall survival than BATF2-negative patients. NPC patients with serum and exosomal BATF2 mRNA expressions made up 51.47 and 48.52% of all patients, respectively. The AUCs of serum and exosomal BATF2 mRNA expressions in discriminating NPC from healthy controls were 0.9409 and 0.8983. Patients who had received radiochemotherapy exhibited higher serum and exosomal BATF2 mRNA expressions versus the levels at baseline as well as those detected in recurrent patients.Conclusion: BATF2 is expressed cancerous tissues, serum, and serum-derived exosomes in NPC patients. Circulating and tissue BATF2 can serve as a multipurpose biomarker capable of the diagnosis, prognosis prediction, efficacy evaluation, and recurrence monitoring in NPC.

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yingying Lin ◽  
Xusheng Zhou ◽  
Wei Peng ◽  
Jing Wu ◽  
Xiufeng Wu ◽  
...  

Abstract Background Basic leucine zipper ATF-like transcription factor 2 (BATF2) has been reported to participate in the occurrence and development of some malignancies. Herein, we aimed to explore the expression pattern and clinical implications of BATF2 in breast cancer (BC). Methods We assessed the differences in BATF2 mRNA expression between cancerous and noncancerous tissues in BC using GEPIA and UALCAN data and in BATF2 protein expression pattern using Human Protein Atlas (HPA) data. BATF2 co-expression networks were analyzed in Coexpedia. The association between the differentially expressed BATF2 mRNA and BC prognosis was assessed using UALCAN, OSbrca, and GEPIA databases. In external validations, BATF2 protein expression in BC tissues was quantitated using a tissue microarray and immunohistochemistry (IHC) analysis, and BATF2 mRNA expression in serum and serum-derived exosomes of BC patients using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results No difference in the BATF2 mRNA expression level was found between cancerous and noncancerous tissues in BC based on databases. There were low-to-moderate levels of increases in BATF2 protein expressions in BC cases from the HPA cohort. BATF2 mRNA expression was negatively correlated with androgen receptor (AR) and positively correlated with BRCA2 DNA repair associated (BRCA2), marker of proliferation Ki-67 (Mki67), and tumor protein p53 (TP53) expressions. Generally, BATF2 mRNA exhibited a non-significant association with BC prognosis; yet the subgroup analyses showed that triple-negative breast cancer (TNBC) patients with high BATF2 mRNA expressions had a longer overall survival (OS). Our IHC analysis revealed a positive rate of BATF2 protein expression of 46.90%, mainly located in the nucleus of cancer cells in BC, and the OS of BC patients with high BATF2 protein expressions was prolonged. The positive rates of BATF2 mRNA expressions in the serum and exosomes were 45.00 and 41.67%, respectively. Besides, the AUCs of serum and exosomal BATF2 mRNA for BC diagnosis were 0.8929 and 0.8869, respectively. Conclusions BC patients exhibit low-to-moderate expressions in BATF2 mRNA expression levels in cancerous tissues. The high BATF2 protein expression can be a potential indicator of a better BC prognosis. Serum and exosomal BATF2 mRNA levels also serve as promising noninvasive biomarkers for BC diagnosis.


2017 ◽  
Vol 114 (36) ◽  
pp. 9683-9688 ◽  
Author(s):  
Liangru Ke ◽  
Hufeng Zhou ◽  
Chong Wang ◽  
Geng Xiong ◽  
Yanqun Xiang ◽  
...  

Nasopharyngeal carcinoma (NPC) most frequently occurs in southern China and southeast Asia. Epidemiology studies link NPC to genetic predisposition, Epstein–Barr virus (EBV) infection, and environmental factors. Genetic studies indicate that mutations in chromatin-modifying enzymes are the most frequent genetic alterations in NPC. Here, we used H3K27ac chromatin immune precipitation followed by deep sequencing (ChIP-seq) to define the NPC epigenome in primary NPC biopsies, NPC xenografts, and an NPC cell line, and compared them to immortalized normal nasopharyngeal or oral epithelial cells. We identified NPC-specific enhancers and found these enhancers were enriched with nuclear factor κB (NF-κB), IFN-responsive factor 1 (IRF1) and IRF2, and ETS family members ETS1 motifs. Normal cell-specific enhancers were enriched with basic leucine zipper family members and TP53 motifs. NPC super-enhancers with extraordinarily broad and high H3K27ac signals were also identified, and they were linked to genes important for oncogenesis including ETV6. ETV6 was also highly expressed in NPC biopsies by immunohistochemistry. High ETV6 expression correlated with a poor prognosis. Furthermore, we defined the EBV episome epigenetic landscapes in primary NPC tissue.


2016 ◽  
pp. 138-140
Author(s):  
S.I. Zhuk ◽  
◽  
O.A. Taran ◽  
A.N. Koshmienskaya ◽  
T.V. Lobastova ◽  
...  

The objective: the finding of protein expression of apoptosis regulator BCL-2, Smooth Muscule Actin and the antigen Ki-67 in cervical intraepithelial neoplasia of different severity to optimize the diagnosis and prognosis of the disease. Patients and methods. The study involved 42 women of reproductive age with cervical intraepithelial the neoplasia of the cervix varying degrees applied to the doctor of cervical pathology Zhitomir regional oncologic dispensary. All women (n=42) were divided into groups. The first group included 15 patients (35.7%) with cervical intraepithelial neoplasia with mild. The second group included 13 women (31%) with cervical intraepithelial neoplasia a moderate degree. The third group was represented by patients with cervical intraepithelial neoplasia with severe – 14 respondents (33.3 per cent). Results. Marker BCL-2 in patients of the first group was positive in 7 patients (46.7%), Smooth Muscule Actin was positive in 9 patients (60%) and Ki-67 was diagnosed in 8 of the surveyed women (53.3%). In the second group of BCL-2 was positive in 8 patients (61.5%), Clone 124, Smooth Muscule Actin, Clone 1A4 was positive in 9 patients (69.2%), and Ki-67 was diagnosed in 12 of the surveyed women (92.3%). Marker BCL-2 in patients of the third group was positive in 12 patients (85.7%), Smooth Muscule Actin was positive in 10 patients (71.4%) and Ki-67 was diagnosed in 13 of the surveyed women (92.9% ). Conclusion. Carcinogenesis is associated with molecular genetic damage to the cervix. Some of the products of this process can be used as prognostic and diagnostic markers of tumor progression. Determination of protein expression of apoptosis regulator BCL-2, Smooth Muscule Actin and the antigen Ki-67 in cervical intraepithelial neoplasia makes it possible to accurately verify the diagnosis and to predict the course of pathological changes in the flat epithelium of the cervix. Key words: cervical intraepithelial neoplasia, cervical cancer, morphological diagnostics of precancerous lesions, BCL-2, Smooth Muscule Actin, Ki-67.


2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098154
Author(s):  
Xin Yuan ◽  
Yize Zhang ◽  
Zujiang Yu

Objective To investigate the association between microRNA-3615 (miR-3615) expression and the prognosis and clinicopathological features in patients with hepatocellular carcinoma (HCC). Methods We obtained clinicopathological and genomic data and prognostic information on HCC patients from The Cancer Genome Atlas (TCGA) database. We then analyzed differences in miR-3615 expression levels between HCC and adjacent tissues using SPSS software, and examined the relationships between miR-3615 expression levels and clinicopathological characteristics. We also explored the influence of miR-3615 expression levels on the prognosis of HCC patients using Kaplan–Meier survival curve analysis. Results Based on data for 345 HCC and 50 adjacent normal tissue samples, expression levels of miR-3615 were significantly higher in HCC tissues compared with adjacent tissues. MiR-3615 expression levels in HCC patients were negatively correlated with overall survival time and positively correlated with high TNM stage, serum Ki-67 expression level, and serum alpha-fetoprotein level. There were no significant correlations between miR-3615 expression and age, sex, and pathological grade. Conclusion MiR-3615 may be a promising new biomarker and prognostic factor for HCC.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Na Sang ◽  
Hui Liu ◽  
Bin Ma ◽  
Xianzhong Huang ◽  
Lu Zhuo ◽  
...  

Abstract Background In plants, 14-3-3 proteins, also called GENERAL REGULATORY FACTORs (GRFs), encoded by a large multigene family, are involved in protein–protein interactions and play crucial roles in various physiological processes. No genome-wide analysis of the GRF gene family has been performed in cotton, and their functions in flowering are largely unknown. Results In this study, 17, 17, 31, and 17 GRF genes were identified in Gossypium herbaceum, G. arboreum, G. hirsutum, and G. raimondii, respectively, by genome-wide analyses and were designated as GheGRFs, GaGRFs, GhGRFs, and GrGRFs, respectively. A phylogenetic analysis revealed that these proteins were divided into ε and non-ε groups. Gene structural, motif composition, synteny, and duplicated gene analyses of the identified GRF genes provided insights into the evolution of this family in cotton. GhGRF genes exhibited diverse expression patterns in different tissues. Yeast two-hybrid and bimolecular fluorescence complementation assays showed that the GhGRFs interacted with the cotton FLOWERING LOCUS T homologue GhFT in the cytoplasm and nucleus, while they interacted with the basic leucine zipper transcription factor GhFD only in the nucleus. Virus-induced gene silencing in G. hirsutum and transgenic studies in Arabidopsis demonstrated that GhGRF3/6/9/15 repressed flowering and that GhGRF14 promoted flowering. Conclusions Here, 82 GRF genes were identified in cotton, and their gene and protein features, classification, evolution, and expression patterns were comprehensively and systematically investigated. The GhGRF3/6/9/15 interacted with GhFT and GhFD to form florigen activation complexs that inhibited flowering. However, GhGRF14 interacted with GhFT and GhFD to form florigen activation complex that promoted flowering. The results provide a foundation for further studies on the regulatory mechanisms of flowering.


Genetics ◽  
1995 ◽  
Vol 141 (4) ◽  
pp. 1275-1285 ◽  
Author(s):  
K N Huang ◽  
L S Symington

Abstract The PKC1 gene product, protein kinase C, regulates a mitogen-activated protein kinase (MAPK) cascade, which is implicated in cell wall metabolism. Previously, we identified the pkc1-4 allele in a screen for mutants with increased rates of recombination, indicating that PKC1 may also regulate DNA metabolism. The pkc1-4 allele also conferred a temperature-sensitive (ts) growth defect. Extragenic suppressors were isolated that suppress both the ts and hyperrecombination phenotypes conferred by the pkc1-4 mutation. Eight of these suppressors for into two complementation groups, designated KCS1 and KCS2. KCS1 was cloned and found to encode a novel protein with homology to the basic leucine zipper family of transcription factors. KCS2 is allelic with PTC1, a previously identified type 2C serine/threonine protein phosphatase. Although mutation of either KCS1 or PTC1 causes little apparent phenotype, the kcs1 delta ptc1 delta double mutant fails to grow at 30 degrees. Furthermore, the ptc1 deletion mutation is synthetically lethal in combination with a mutation in MPK1, which encodes a MAPK homologue proposed to act in the PKC1 pathway. Because PTC1 was initially isolated as a component of the Hog1p MAPK pathway, it appears that these two MAPK cascades share a common regulatory feature.


Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2323
Author(s):  
Anita Thomas ◽  
Sascha Reetz ◽  
Philipp Stenzel ◽  
Katrin Tagscherer ◽  
Wilfried Roth ◽  
...  

The PI3K/mTOR/AKT pathway might represent an intriguing option for treatment of penile cancer (PeCa). We aimed to assess whether members of this pathway might serve as biomarkers and targets for systemic therapy. Tissue of primary cancer from treatment-naïve PeCa patients was used for tissue microarray analysis. Immunohistochemical staining was performed with antibodies against AKT, pAKT, mTOR, pmTOR, pS6, pPRAS, p4EBP1, S6K1 and pp70S6K. Protein expression was correlated with clinicopathological characteristics as well as overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS) and metastasis-free survival (MFS). AKT inhibition was tested in two primarily established, treatment-naïve PeCa cell lines by treatment with capivasertib and analysis of cell viability and chemotaxis. A total of 76 patients surgically treated for invasive PeCa were included. Higher expression of AKT was significantly more prevalent in high-grade tumors and predictive of DSS and OS in the Kaplan–Meier analysis, and an independent predictor of worse OS and DSS in the multivariate regression analysis. Treatment with pan-AKT inhibitor capivasertib in PeCa cell lines induced a significant downregulation of both total AKT and pAKT as well as decreased cell viability and chemotaxis. Selected protein candidates of the mTOR/AKT signaling pathway demonstrate association with histological and survival parameters of PeCa patients, whereas AKT appears to be the most promising one.


Sign in / Sign up

Export Citation Format

Share Document