1.
Front Oncol. 2020 Feb 26;10:131. doi: 10.3389/fonc.2020.00131. eCollection 2020.
Real-World Impact of Surgical Excision on Overall Survival in Primary Central Nervous System Lymphoma.
Abstract
Substantial controversy still exists regarding the use of surgical excision in the treatment of primary central nervous system lymphoma (PCNSL). This study was aimed to evaluate the survival benefit of surgical excision in PCNSL patients based on a US population. Using the Surveillance, Epidemiology, and End Results (SEER) Program database, a total of 3,543 PCNSL patients were identified from 2000 to 2014 for analysis. Surgical excision was accessed via Kaplan-Meier and multivariate Cox regression survival analyses. Coarsened exact matching (CEM) analysis was additionally employed to intensify our findings. Finally, we found that surgical excision was significantly associated with increased survival over no surgery/biopsy (P < 0.001), and its survival benefit was also independent of baseline prognostic factors. The survival benefit of surgery was also validated in clinically important subsets. CEM analysis further validated the survival advantage of surgery (P < 0.001). Moreover, a novel prediction model with excellent performance was established to estimate the potential benefit from surgical excision of the lesion with respect to the end point of overall survival. The current study supports the favorable impact of surgical excision on clinical outcome in patients with PCNSL. Although further randomized controlled trials are warranted, currently available evidence should be considered in the clinical management of this disease.
Copyright © 2020 Deng, Xu, Lin, Zhang, Yu, Sheng, Yin, Zhang and Lin.
KEYWORDS:
SEER; nomogram; primary central nervous system lymphoma; surgery; survival
- PMID:
- 32176222
- PMCID:
- PMC7054438
- DOI:
- 10.3389/fonc.2020.00131
2.
Front Oncol. 2020 Feb 27;10:267. doi: 10.3389/fonc.2020.00267. eCollection 2020.
RNA-seq Analysis of Wild-Type vs. FOXC2-Deficient Melanoma Cells Reveals a Role for the FOXC2 Transcription Factor in the Regulation of Multiple Oncogenic Pathways.
KEYWORDS:
FOXC2; RNA-seq; differential expression; gene regulation; melanoma; oncogene
- PMID:
- 32175283
- PMCID:
- PMC7056877
- DOI:
- 10.3389/fonc.2020.00267
3.
Front Oncol. 2020 Feb 27;10:242. doi: 10.3389/fonc.2020.00242. eCollection 2020.
Analytical Low-Dose CBCT Reconstruction Using Non-local Total Variation Regularization for Image Guided Radiation Therapy.
Abstract
Purpose: Conventional iterative low-dose CBCT reconstruction techniques are slow and tend to over-smooth edges through uniform weighting of the image penalty gradient. In this study, we present a non-iterative analytical low-dose CBCT reconstruction technique by restoring the noisy low-dose CBCT projection with the non-local total variation (NLTV) method. Methods: We modeled the low-dose CBCT reconstruction as recovering high quality, high-dose CBCT x-ray projections (100 kVp, 1.6 mAs) from low-dose, noisy CBCT x-ray projections (100 kVp, 0.1 mAs). The restoration of CBCT projections was performed using the NLTV regularization method. In NLTV, the x-ray image is optimized by minimizing an energy function that penalizes gray-level difference between pair of pixels between noisy x-ray projection and denoising x-ray projection. After the noisy projection is restored by NLTV regularization, the standard FDK method was applied to generate the final reconstruction output. Results: Significant noise reduction was achieved comparing to original, noisy inputs while maintaining the image quality comparable to the high-dose CBCT projections. The experimental validations show the proposed NLTV algorithm can robustly restore the noise level of x-ray projection images while significantly improving the overall image quality. The improvement in normalized mean square error (NMSE) and peak signal-to-noise ratio (PSNR) measured from the non-local total variation-gradient projection (NLTV-GPSR) algorithm is noticeable compared to that of uncorrected low-dose CBCT images. Moreover, the difference of CNRs from the gains from the proposed algorithm is noticeable and comparable to high-dose CBCT. Conclusion: The proposed method successfully restores noise degraded, low-dose CBCT projections to high-dose projection quality. Such an outcome is a considerable improvement to the reconstruction result compared to the FDK-based method. In addition, a significant reduction in reconstruction time makes the proposed algorithm more attractive. This demonstrates the potential use of the proposed algorithm for clinical practice in radiotherapy.
Copyright © 2020 Sohn, Kim, Kim, Lee, Zhou, Yang and Liu.
KEYWORDS:
compressed sensing; image reconstruction; image-guided radiation therapy (IGRT); low-dose CBCT; non-local total variation
- PMID:
- 32175282
- PMCID:
- PMC7056884
- DOI:
- 10.3389/fonc.2020.00242
4.
Front Oncol. 2020 Feb 26;10:239. doi: 10.3389/fonc.2020.00239. eCollection 2020.
Cross-Talk Between the Tumor Microenvironment, Extracellular Matrix, and Cell Metabolism in Cancer.
Abstract
The extracellular matrix (ECM) is a complex network of secreted proteins which provides support for tissues and organs. Additionally, the ECM controls a plethora of cell functions, including cell polarity, migration, proliferation, and oncogenic transformation. One of the hallmarks of cancer is altered cell metabolism, which is currently being exploited to develop anti-cancer therapies. Several pieces of evidence indicate that the tumor microenvironment and the ECM impinge on tumor cell metabolism. Therefore, it is essential to understand the contribution of the complex 3D microenvironment in controlling metabolic plasticity and responsiveness to therapies targeting cell metabolism. In this mini-review, we will describe how the tumor microenvironment and cancer-associated fibroblasts dictate cancer cell metabolism, resulting in increased tumor progression. Moreover, we will define the cross-talk between nutrient signaling and the trafficking of the ECM receptors of the integrin family. Finally, we will present recent data highlighting the contribution of nutrient scavenging from the microenvironment to support cancer cells growth under nutrient starvation conditions.
Copyright © 2020 Nazemi and Rainero.
KEYWORDS:
cancer associated fibroblasts; cell metabolism; extracellular matrix; nutrient scavenging; nutrient signaling
- PMID:
- 32175281
- PMCID:
- PMC7054479
- DOI:
- 10.3389/fonc.2020.00239
5.
Front Oncol. 2020 Feb 27;10:238. doi: 10.3389/fonc.2020.00238. eCollection 2020.
RNY4 in Circulating Exosomes of Patients With Pediatric Anaplastic Large Cell Lymphoma: An Active Player?
Lovisa F1,2, Di Battista P1,2, Gaffo E3, Damanti CC1,2, Garbin A1,2, Gallingani I1,2, Carraro E1, Pillon M1, Biffi A1,2,4, Bortoluzzi S3,5, Mussolin L1,2.
Abstract
Emerging evidence indicates that extracellular vesicles, particularly exosomes, play a role in several biological processes and actively contribute to cancer development and progression, by carrying and delivering proteins, transcripts and small RNAs (sRNAs). There is high interest in studying exosomes of cancer patients both to develop non-invasive liquid biopsy tests for risk stratification and to elucidate their possible involvement in disease mechanisms. We profiled by RNA-seq the sRNA content of circulating exosomes of 20 pediatric patients with Anaplastic Large Cell Lymphoma (ALCL) and five healthy controls. Our analysis disclosed that non-miRNA derived sRNAs constitute the prominent fraction of sRNA loaded in exosomes and identified 180 sRNAs significantly more abundant in exosomes of ALCL patients compared to controls. YRNA fragments, accounting for most of exosomal content and being significantly increased in ALCL patients, were prioritized for further investigation by qRT-PCR. Quantification of RNY4 fragments and full-length sequences disclosed that the latter are massively loaded into exosomes of ALCL patients with more advanced and aggressive disease. These results are discussed in light of recent findings on the role of RNY4 in the modulation of tumor microenvironment.
Copyright © 2020 Lovisa, Di Battista, Gaffo, Damanti, Garbin, Gallingani, Carraro, Pillon, Biffi, Bortoluzzi and Mussolin.
KEYWORDS:
ALCL; RNA-seq; YRNA; exosomes; liquidbiopsy; small RNA
- PMID:
- 32175280
- PMCID:
- PMC7056873
- DOI:
- 10.3389/fonc.2020.00238
6.
Front Oncol. 2020 Feb 27;10:228. doi: 10.3389/fonc.2020.00228. eCollection 2020.
Reversal Effect of ALK Inhibitor NVP-TAE684 on ABCG2-Overexpressing Cancer Cells.
Wang J1,2, Wang JQ1, Cai CY1, Cui Q1,3, Yang Y1, Wu ZX1, Dong X1, Zeng L1,4, Zhao L2, Yang DH1, Chen ZS1.
Abstract
Failure of cancer chemotherapy is mostly due to multidrug resistance (MDR). Overcoming MDR mediated by overexpression of ATP binding cassette (ABC) transporters in cancer cells remains a big challenge. In this study, we explore whether NVP-TAE684, a novel ALK inhibitor which has the potential to inhibit the function of ABC transport, could reverse ABC transporter-mediated MDR. MTT assay was carried out to determine cell viability and reversal effect of NVP-TAE684 in parental and drug resistant cells. Drug accumulation and efflux assay was performed to examine the effect of NVP-TAE684 on the cellular accumulation and efflux of chemotherapeutic drugs. The ATPase activity of ABCG2 transporter in the presence or absence of NVP-TAE684 was conducted to determine the impact of NVP-TAE684 on ATP hydrolysis. Western blot analysis and immunofluorescence assay were used to investigate protein molecules related to MDR. In addition, the interaction between NVP-TAE684 and ABCG2 transporter was investigated via in silico analysis. MTT assay showed that NVP-TAE684 significantly decreased MDR caused byABCG2-, but not ABCC1-transporter. Drug accumulation and efflux tests indicated that the effect of NVP-TAE684 in decreasing MDR was due to the inhibition of efflux function of ABCG2 transporter. However, NVP-TAE684 did not alter the expression or change the subcellular localization of ABCG2 protein. Furthermore, ATPase activity analysis indicated that NVP-TAE684 could stimulate ABCG2 ATPase activity. Molecular in silico analysis showed that NVP-TAE684 interacts with the substrate binding sites of the ABCG2 transporter. Taken together, our study indicates that NVP-TAE684 could reduce the resistance of MDR cells to chemotherapeutic agents, which provides a promising strategy to overcome MDR.
Copyright © 2020 Wang, Wang, Cai, Cui, Yang, Wu, Dong, Zeng, Zhao, Yang and Chen.
KEYWORDS:
ABCG2; ALK inhibitor; ATP-binding cassette (ABC) transporter; NVP-TAE684; multidrug resistance (MDR)
- PMID:
- 32175279
- PMCID:
- PMC7056829
- DOI:
- 10.3389/fonc.2020.00228
7.
Front Oncol. 2020 Feb 27;10:221. doi: 10.3389/fonc.2020.00221. eCollection 2020.
Resistance Mechanisms to Anti-angiogenic Therapies in Cancer.
Abstract
Tumor growth and metastasis rely on tumor vascular network for the adequate supply of oxygen and nutrients. Tumor angiogenesis relies on a highly complex program of growth factor signaling, endothelial cell (EC) proliferation, extracellular matrix (ECM) remodeling, and stromal cell interactions. Numerous pro-angiogenic drivers have been identified, the most important of which is the vascular endothelial growth factor (VEGF). The importance of pro-angiogenic inducers in tumor growth, invasion and extravasation make them an excellent therapeutic target in several types of cancers. Hence, the number of anti-angiogenic agents developed for cancer treatment has risen over the past decade, with at least eighty drugs being investigated in preclinical studies and phase I-III clinical trials. To date, the most common approaches to the inhibition of the VEGF axis include the blockade of VEGF receptors (VEGFRs) or ligands by neutralizing antibodies, as well as the inhibition of receptor tyrosine kinase (RTK) enzymes. Despite promising preclinical results, anti-angiogenic monotherapies led only to mild clinical benefits. The minimal benefits could be secondary to primary or acquired resistance, through the activation of alternative mechanisms that sustain tumor vascularization and growth. Mechanisms of resistance are categorized into VEGF-dependent alterations, non-VEGF pathways and stromal cell interactions. Thus, complementary approaches such as the combination of these inhibitors with agents targeting alternative mechanisms of blood vessel formation are urgently needed. This review provides an updated overview on the pathophysiology of angiogenesis during tumor growth. It also sheds light on the different pro-angiogenic and anti-angiogenic agents that have been developed to date. Finally, it highlights the preclinical evidence for mechanisms of angiogenic resistance and suggests novel therapeutic approaches that might be exploited with the ultimate aim of overcoming resistance and improving clinical outcomes for patients with cancer.
Copyright © 2020 Haibe, Kreidieh, El Hajj, Khalifeh, Mukherji, Temraz and Shamseddine.
KEYWORDS:
VEGF; VEGF-R; angiogenesis; bevacizumab; colorectal cancer; resistance mechanisms
- PMID:
- 32175278
- PMCID:
- PMC7056882
- DOI:
- 10.3389/fonc.2020.00221
8.
Front Oncol. 2020 Feb 27;10:220. doi: 10.3389/fonc.2020.00220. eCollection 2020.
An Overview of Vasculogenic Mimicry in Breast Cancer.
Andonegui-Elguera MA1, Alfaro-Mora Y2, Cáceres-Gutiérrez R1, Caro-Sánchez CHS3, Herrera LA1,4, Díaz-Chávez J1.
Abstract
Vasculogenic mimicry (VM) is the formation of vascular channels lacking endothelial cells. These channels are lined by tumor cells with cancer stem cell features, positive for periodic acid-Schiff, and negative for CD31 staining. The term VM was introduced by Maniotis et al. (1), who reported this phenomenon in highly aggressive uveal melanomas; since then, VM has been associated with poor prognosis, tumor aggressiveness, metastasis, and drug resistance in several tumors, including breast cancer. It is proposed that VM and angiogenesis (the de novo formation of blood vessels from the established vasculature by endothelial cells, which is observed in several tumors) rely on some common mechanisms. Furthermore, it is also suggested that VM could constitute a means to circumvent anti-angiogenic treatment in cancer. Therefore, it is important to determinant the factors that dictate the onset of VM. In this review, we describe the current understanding of VM formation in breast cancer, including specific signaling pathways, and cancer stem cells. In addition, we discuss the clinical significance of VM in prognosis and new opportunities of VM as a target for breast cancer therapy.
Copyright © 2020 Andonegui-Elguera, Alfaro-Mora, Cáceres-Gutiérrez, Caro-Sánchez, Herrera and Díaz-Chávez.
KEYWORDS:
angiogenesis; breast cancer; cancer stem cell; epithelial-mesenchymal transition; triple negative breast cancer; vasculogenic mimicry
- PMID:
- 32175277
- PMCID:
- PMC7056883
- DOI:
- 10.3389/fonc.2020.00220
9.
Front Oncol. 2020 Feb 27;10:209. doi: 10.3389/fonc.2020.00209. eCollection 2020.
The Atypical Protein Kinase C Small Molecule Inhibitor ζ-Stat, and Its Effects on Invasion Through Decreases in PKC-ζ Protein Expression.
Abstract
Ovarian cancer is estimated to reach 22,530 diagnoses and cause 13,980 cancer deaths per year. The most common histology diagnosed of ovarian cancer is epithelial ovarian carcinomas (EOC). An aggressive epithelial subtype is clear cell ovarian carcinoma (CCOC) and is characterized as a non-serous ovarian cancer. Protein kinase C (PKC) is an enzymatic family of proteins that have been found to be a component in cancer progression, tissue invasion, and metastasis. The atypical PKC (aPKC) isoforms, PKC-ι and PKC-ζ, have been suggested to participate in the increased proliferation of ovarian cancers. Previous studies have indicated that novel aPKC inhibitors ICA-1S and ζ-Stat decreased the migratory behaviors of colorectal cancer cells and were selective for PKC-ι/λ and PKC-ζ, respectively. The aims of this investigation were to further determine the binding mechanisms of ζ-Stat, expand on the tissue range of these compounds, investigate the therapeutic potential of ζ-Stat in CCOC, and to illustrate the disruption of invasion via the PKC-ζ signaling cascade. The methods utilized were molecular docking and virtual target screening, Western blot analysis, end-point PCR, GST pull down, cell viability and invasion and migration assays. We discovered that the small molecule inhibitor, ζ-Stat, is a prospective drug candidate to investigate as a novel potential treatment for CCOC. We also found that the PKC-ζ/Ect2/Rac1 activation pathway was decreased by ζ-Stat, which in turn decreased invasive behavior of CCOC.
Copyright © 2020 Smalley, Metcalf, Patel, Islam, Bommareddy and Acevedo-Duncan.
KEYWORDS:
Ect2; PKC-zeta; PKC-ζ; clear cell ovarian carcinoma (CCOC); computational molecular modeling; zeta-Stat; ζ-Stat
- PMID:
- 32175276
- PMCID:
- PMC7056911
- DOI:
- 10.3389/fonc.2020.00209
10.
Front Oncol. 2020 Feb 27;10:204. doi: 10.3389/fonc.2020.00204. eCollection 2020.
SPRED1 Is Downregulated and a Prognostic Biomarker in Adult Acute Myeloid Leukemia.
Abstract
We report herein that Sprouty-Related EVH1 Domain-Containing Protein1 (SPRED1) is downregulated and a prognostic biomarker in adult acute myeloid leukemia (AML). We determined mRNA levels of SPRED1 in the bone marrow mononuclear cells from adult patients, including 113 AMLs and 22 acute lymphoblastic leukemias (ALLs), as well as in 37 healthy control subjects. Significantly decreased SPRED1 mRNA expression was found in AML patients comparing to those in ALL patients and healthy controls, which was confirmed by immunocytochemistry analysis of SPRED1 protein and ELISA measurement of serum SPRED1 level. Further analysis demonstrated that SPRED1 expression was significantly higher for most patients at complete remission after induction treatment than at diagnosis. Moreover, SPRED1 expression was significantly downregulated in M2 and M3 types. Non-acute promyelocytic leukemia (non-APL) patients with decreased SPRED1 had significantly lower 2-year progression-free survival and event-free survival rates. In vitro, ectopic overexpression of SPRED1 leads to a decrease of extracellular signal-regulated kinase (ERK) phosphorylation, induction of apoptosis and reduction of proliferation of THP-1 cells. Our findings suggest SPRED1 is not only a predictor of treatment response, but also an independent prognostic factor for non-APL, and targeting Ras- Mitogen-activated protein kinase (MAPK) signaling may be a promising strategy for the treatment of AML with downregulation of SPRED1.
Copyright © 2020 Zhang, Zhang, Lu, Xu, Wang, Mo, Pang, Tang, Li, Yan and Li.
KEYWORDS:
AML; MAPK; MIR126; SPRED1; non-APL
- PMID:
- 32175275
- PMCID:
- PMC7056905
- DOI:
- 10.3389/fonc.2020.00204
11.
Front Oncol. 2020 Feb 27;10:203. doi: 10.3389/fonc.2020.00203. eCollection 2020.
Prostate Fiducial Marker Placement in Patients on Anticoagulation: Feasibility Prior to Prostate SBRT.
Iocolano M1,2, Blacksburg S1, Carpenter T1, Repka M1, Carbone S1, Demircioglu G1, Miccio M1, Katz A3, Haas J1.
Abstract
Background and Purpose: Fiducial marker placement is required in patients undergoing robotic-based Stereotactic Body Radiotherapy (SBRT) or image-guided radiation therapy (IGRT) for prostate cancer. Many patients take antiplatelet or anticoagulant medication due to other medical comorbidities. They are often required to temporarily discontinue these medications prior to invasive medical procedures as they are prone to bleed. Some patients are unable to discontinue therapy due to an elevated risk of thromboembolic events. The purpose of this study is to report this institution's experience placing fiducial markers in prostate cancer patients who are on chronic antiplatelet or anticoagulant medication. Materials and Methods: From August 2015-March 2019 57 patients on chronic antiplatelet or anticoagulation therapy who were not cleared to stop these medications underwent transrectal ultrasound guided (TRUS) fiducial marker placement for SBRT/IGRT. All patients were monitored by a registered nurse during the procedure for prolonged bleeding that required staff to hold pressure to the area with a 4 × 4 gauze until it resolved. All patients were also called the following day to assess for ongoing bleeding events. Treatment planning CT scan confirmed the ideal geometry of the marker placement. Results: All 57 patients on antiplatelet or anticoagulant medication who underwent fiducial marker placement were discharged home the same day of the procedure. Four patients experienced persistent bleeding that required a nurse to hold prolonged pressure to the area. No patient experienced significant bleeding the following day or any untoward cardiovascular event. Conclusions: This series suggests the use of antiplatelet or anticoagulant medication is not an absolute contraindication to fiducial marker placement in patients undergoing SBRT or IGRT for prostate cancer. These patients should be closely monitored after the procedure for bleeding complications. Practitioners may consider the patient's medical comorbidities, risk factors for thromboembolism, and overall functional status as there is no standardized protocol for discontinuing anticoagulant or antiplatelet therapy for fiducial marker placement.
Copyright © 2020 Iocolano, Blacksburg, Carpenter, Repka, Carbone, Demircioglu, Miccio, Katz and Haas.
KEYWORDS:
SBRT; anticoagulants; fiducial markers; image-guided; prostate cancer; radiotherapy
- PMID:
- 32175274
- PMCID:
- PMC7056879
- DOI:
- 10.3389/fonc.2020.00203
12.
Front Oncol. 2020 Feb 27;10:185. doi: 10.3389/fonc.2020.00185. eCollection 2020.
Computational Methods for the Integrative Analysis of Genomics and Pharmacological Data.
Abstract
Since the pioneering NCI-60 panel of the late'80's, several major screenings of genetic profiling and drug testing in cancer cell lines have been conducted to investigate how genetic backgrounds and transcriptional patterns shape cancer's response to therapy and to identify disease-specific genes associated with drug response. Historically, pharmacogenomics screenings have been largely heterogeneous in terms of investigated cell lines, assay technologies, number of compounds, type and quality of genomic data, and methods for their computational analysis. The analysis of this enormous and heterogeneous amount of data required the development of computational methods for the integration of genomic profiles with drug responses across multiple screenings. Here, we will review the computational tools that have been developed to integrate cancer cell lines' genomic profiles and sensitivity to small molecule perturbations obtained from different screenings.
Copyright © 2020 Caroli, Dori and Bicciato.
KEYWORDS:
bioinformatics; genomics; integration; online databases; pharmacogenomics
- PMID:
- 32175273
- PMCID:
- PMC7056894
- DOI:
- 10.3389/fonc.2020.00185
13.
Front Oncol. 2020 Feb 27;10:149. doi: 10.3389/fonc.2020.00149. eCollection 2020.
FBXW4 Is Highly Expressed and Associated With Poor Survival in Acute Myeloid Leukemia.
Abstract
The F-box and WD repeat domain-containing (FBXW) proteins play an important role in ubiquitin proteasome by inducing protein degradation. Ten FBXW proteins have been identified in humans. The functions of FBXW proteins, like FBXW7, have been well-established in many human cancers. However, little is known about their transcriptional expression profiles and relationship with prognosis in acute myeloid leukemia (AML). Here we investigated the roles of FBXW proteins in AML by analyzing their mRNA expression profiles and association with clinical features using data from EMBL-EBI, the Cancer Cell Line Encyclopedia, Gene Expression Profiling Interactive Analysis, and cBioPortal databases. Our results showed that the mRNA level of FBXW proteins were highly detected by microarray in 14 AML cell lines, although there were no obvious differences. The expression of FBXW4 was significantly higher in AML patients compared with that in normal controls (P < 0.01). Patients whose age was ≥60 years old had a higher FBXW4 expression when compared with those who were <60 years old (P < 0.05). Cytogenetic favorable-risk group patients had a much lower FBXW4 expression than the intermediate- and poor-risk group patients (P < 0.0001). Moreover, patients with high FBXW4 expression exhibited significantly shorter event-free survival (EFS) and overall survival (OS) than those with low FBXW4 expression (median EFS: 5.3 vs. 10.0 months, P = 0.025; median OS: 8.1 vs. 19.0 months, P= 0.015). A multivariate analysis indicated that high FBXW4 expression was an independent risk factor for poor EFS in AML patients who received intensive chemotherapy followed by allo-SCT. In summary, our data suggested that FBXW4 is aberrantly expressed in AML and high FBXW4 expression might be a poor prognostic biomarker; future functional and mechanistic studies will further illuminate the roles of FBXW4 in AML.
Copyright © 2020 Han, Zhang, Song, Bamme, Song and Ge.
KEYWORDS:
FBXW4; acute myeloid leukemia; clinical feature; expression; survival
- PMID:
- 32175272
- PMCID:
- PMC7056870
- DOI:
- 10.3389/fonc.2020.00149
14.
Front Oncol. 2020 Feb 26;10:115. doi: 10.3389/fonc.2020.00115. eCollection 2020.
METTL3 Promotes the Progression of Gastric Cancer via Targeting the MYC Pathway.
Abstract
Methyltransferase-like 3 (METTL3), a major component of the N6-methyladenosine (m6A) methyltransferase complex, has been suggested to function as an oncogene in several cancers. However, its biological mechanism and the involved pathways in gastric cancer (GC) remain unknown. Here, we reported that frequent upregulation of METTL3 was responsible for the aberrant m6A levels in gastric carcinoma. On the other hand, a high level of METTL3 was significantly associated with several clinicopathological features and poor survival in patients with GC. The knockdown of METTL3 effectively inhibited cell proliferation and migration and invasion capacity. Moreover, overexpression of METTL3 considerably augmented its oncogenic function. Integrated RNA-seq and m6A-seq analysis first indicated that several component molecules (e.g., MCM5, MCM6, etc.) of MYC target genes were mediated by METTL3 via altered m6A modification. Our work uncovers the oncogenic roles of METTL3 in GC and suggests a critical mechanism of GC progression.
Copyright © 2020 Yang, Chen, Yu, Lu, Wu, Wang, Ju, Xu, Liu and Zeng.
KEYWORDS:
METTL3; MYC target genes; gastric cancer; minichromosome maintenance complex component 5; minichromosome maintenance complex component 6; prognostic factor
- PMID:
- 32175271
- PMCID:
- PMC7054453
- DOI:
- 10.3389/fonc.2020.00115
15.
Front Oncol. 2020 Feb 27;10:112. doi: 10.3389/fonc.2020.00112. eCollection 2020.
Differentiation of Thyroid Nodules Difficult to Diagnose With Contrast-Enhanced Ultrasonography and Real-Time Elastography.
Xi X1, Gao L2, Wu Q2,3, Fang S3, Xu J4, Liu R2, Yang X2, Zhu S2, Zhao R2, Lai X2, Zhang X2, Zhang B1,2, Jiang Y2.
Abstract
According to the 2015 American Thyroid Association (ATA), referred risk stratification and thyroid nodules with intermediate- and low-suspicion patterns are difficult to diagnose. The objective of this study is to evaluate the diagnostic performance of contrast-enhanced ultrasonography (CEUS) and elastosonography (ES) for the differentiation of these thyroid nodules. From November 2011 to June 2016, a total of 163 thyroid nodules with intermediate- and low-suspicion patterns in 150 consecutive patients at our hospital were studied before surgery. With surgical pathology as the standard, the diagnostic value of CEUS and ES was analyzed. There were 29 (17.8%) malignant lesions and 134 (82.2%) benign lesions. The enhancement patterns of CEUS, the echogenicity, and the elastography were significantly different between malignant and benign lesions (P < 0.05). Heterogenous enhancement was more common in malignant nodules, and the sensitivity, specificity, positive predictive value, negative predictive value, and odds ratio were 51.7, 88.1, 48.4, 89.4, and 10.1%, respectively. The diagnostic accuracy of CEUS was better than the conventional ultrasound [area under the curve (AUC), 0.729 vs. 0.616, P = 0.021]. The enhancement patterns of CEUS were helpful in the differential diagnosis of thyroid nodules with intermediate and low suspicion.
Copyright © 2020 Xi, Gao, Wu, Fang, Xu, Liu, Yang, Zhu, Zhao, Lai, Zhang, Zhang and Jiang.
KEYWORDS:
American Thyroid Association; contrast-enhanced ultrasonography; elastosonography; intermediate- and low-suspicion patterns; thyroid carcinoma
- PMID:
- 32175270
- PMCID:
- PMC7056834
- DOI:
- 10.3389/fonc.2020.00112
16.
Front Oncol. 2020 Feb 26;10:108. doi: 10.3389/fonc.2020.00108. eCollection 2020.
miR-15b-5p Promotes Growth and Metastasis in Breast Cancer by Targeting HPSE2.
Abstract
MicroRNAs (miRNAs) can participate in many behaviors of various tumors. Prior studies have reported that miR-15b-5p in different tumors can either promote or inhibit tumor progression. In breast cancer, the role of miR-15b-5p is unclear. The main objective of this paper is to explore miR-15b-5p effects and their mechanisms in breast cancer using both in vitro and in vivo experiments. This study showed that miR-15b-5p expression was upregulated in breast cancer compared with normal breast tissue and was positively correlated with poor overall survival in patients. Knockdown of miR-15b-5p in MCF-7 and MD-MBA-231 breast cancer cells restrained cell growth and invasiveness and induced apoptosis, whereas overexpression of miR-15b-5p achieved the opposite effects. We next revealed a negative correlation between miR-15b-5p and heparanase-2 (HPSE2) expression in breast cancer. Knockdown of miR-15b-5p significantly increased HPSE2 expression at both mRNA and protein levels in breast cancer cells in vitro. The underlying mechanisms of miR-15-5p in breast cancer were investigated using luciferase activity reporter assay and rescue experiments. In addition, miR-15b-5p knockdown significantly inhibited tumor growth in a xenograft model in mice. In summary, we showed that miR-15b-5p promotes breast cancer cell proliferation, migration, and invasion by directly targeting HPSE2. Accordingly, miR-15b-5p may serve both as a tool for prognosis and as a target for therapy of breast cancer patients.
Copyright © 2020 Wu, Liu, Jin, Yang, Zhang, Ding, Zhou, Pan and Wei.
KEYWORDS:
HPSE2; biomarker; breast cancer; miR-15b-5p; microRNA
- PMID:
- 32175269
- PMCID:
- PMC7054484
- DOI:
- 10.3389/fonc.2020.00108
17.
Front Oncol. 2020 Feb 27;10:96. doi: 10.3389/fonc.2020.00096. eCollection 2020.
Young-Onset Early Colorectal Cancer Had Similar Relative Survival to but Better Overall Survival Than Conventional Early Colorectal Cancer: A Large Population-Based Study.
Abstract
Background: There existed limited evidence about prognosis of young-onset early colorectal cancer (ECRC). In the present study, we aimed to compare prognosis between patients with young-onset ECRCs and patients with conventional ECRCs. Method: Patients with surgically resected, histologically diagnosed ECRCs were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Young-onset ECRC was defined as ECRC occurring in patients aged <50 years. Five-years relative survival was calculated at the time of diagnosed year and linear regression was performed to analyze the association between 5-years relative survival and age. The multivariate Cox regression, multivariate competing risk model, and propensity score matching (PSM) and univariate analysis weighted by the inverse probability of treatment weight (IPTW) were used to compare overall survival (OS) between young-onset ECRCs and conventional ECRCs. Results: A total of 51,197 ECRCs were retrieved from SEER database, including 4,634 young-onset ECRCs and 46,563 conventional ECRCs. Five-years relative survival was found to be moderately associated with different age groups (R = -0.725, P = 0.0034). Patients with young-onset ECRCs (96.7%) had similar 5-years relative survival compared with conventional ECRCs (96.3%). However, multivariate Cox regression [HR (hazard ratio), 0.18; 95% CI: 0.16-0.20; P < 0.001] showed better OS in young-onset ECRCs. After PSM, we still found favored prognosis for young-onset ECRCs under univariate Cox regression (HR, 0.18; 95% CI: 0.16-0.21; P < 0.001). Similar results could also be found in the univariate Cox regression weighted by IPTW (HR, 0.17; 95% CI: 0.17-0.18; P < 0.001). Conclusions: Patients with young-onset ECRCs had similar relative survival but better OS compared with conventional ECRCs.
Copyright © 2020 Chen, Zhang, Pan, Wang, Zhang and Li.
KEYWORDS:
cause-specific survival; early colorectal cancer; prognosis; relative survival; young-onset
- PMID:
- 32175268
- PMCID:
- PMC7056900
- DOI:
- 10.3389/fonc.2020.00096
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