High Expression of LGR6 is A Poor Prognostic Factor In Esophageal Carcinoma DOI Creative Commons

Takehito Ehara,

Takeshi Uehara, Takahiro Yoshizawa

et al.

Research Square (Research Square), Journal Year: 2021, Volume and Issue: unknown

Published: Dec. 1, 2021

Abstract Background: Leucine-rich repeat-containing G-protein-coupled receptor 6 (LGR6) promotes carcinogenesis and progression in some cancer types. However, there are few reports of LGR6 expression esophageal squamous cell carcinoma (ESCC). clinicopathological features ESCC were investigated by RNAscope, a high-sensitivity RNA situ hybridization method. Methods: Appropriate tumors selected from 41 cases which tissue microarrays generated, was identified RNAscope. Results: Thirty-seven patients had expression. High observed 17 low 24 cases. significantly higher high histological grade than ( P =0.0023). who received neoadjuvant chemotherapy those without =0.0109). Furthermore, showed poorer prognosis (log-rank test, =0.0365). Conclusions: may be prognostic factor potential new therapeutic target ESCC.

Language: Английский

Investigating the Interactions of Glioma Stem Cells in the Perivascular Niche at Single‐Cell Resolution using a Microfluidic Tumor Microenvironment Model DOI
Emmanuela Adjei‐Sowah, Samantha O’Connor, Jaimeson Veldhuizen

et al.

Advanced Science, Journal Year: 2022, Volume and Issue: 9(21)

Published: May 26, 2022

The perivascular niche (PVN) is a glioblastoma tumor microenvironment (TME) that serves as safe haven for glioma stem cells (GSCs), and acts reservoir inevitably leads to recurrence. Understanding cellular interactions in the PVN drive GSC treatment resistance stemness crucial develop lasting therapies glioblastoma. limitations of vivo models vitro assays have led critical knowledge gaps regarding influence various cell types on GSCs behavior. This study developed an organotypic triculture microfluidic model means recapitulate its impact GSCs. platform, comprised endothelial (ECs), astrocytes, GSCs, used investigate invasion, proliferation stemness. Both ECs astrocytes significantly increased invasiveness futher identified 15 ligand-receptor pairs using single-cell RNAseq with putative chemotactic mechanisms where receptor up-regulated diffusible ligand expressed either or ECs. Notably, pair SAA1-FPR1 demonstrated be involved invasion toward PVN. novel platform presented herein can therapeutic development discovery molecular driving biology.

Language: Английский

Citations

29
β-Catenin is required for radial cell patterning and identity in the developing mouse cochlea DOI Open Access

Lina Jansson,

Michael Ebeid, Jessica W. Shen

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2019, Volume and Issue: 116(42), P. 21054 - 21060

Published: Sept. 30, 2019

Significance The cochlea is essential for sound detection. It consists of highly differentiated hair cells and nonsensory supporting radially patterned into lateral medial compartments. However, mechanisms regulating radial patterning specification cell subtypes, each which serves unique functions, are unclear. Here we show that β-catenin required differentiation sensory subtypes in the developing cochlea. β-Catenin-deleted cochleae displayed disrupted compartment borders containing ectopic whereas inhibiting transcriptional preserving adhesion-mediated activities maintained identity. This study thus characterizes a role β-catenin-mediated adhesion

Language: Английский

Citations

32
LGR5 promotes tumorigenicity and invasion of glioblastoma stem‐like cells and is a potential therapeutic target for a subset of glioblastoma patients DOI
Yuan Xie, Anders Sundström,

Naga Prathyusha Maturi

et al.

The Journal of Pathology, Journal Year: 2018, Volume and Issue: 247(2), P. 228 - 240

Published: Oct. 25, 2018

Abstract Glioblastoma (GBM) is the most common and lethal primary malignant brain tumor which lacks efficient treatment predictive biomarkers. Expression of epithelial stem cell marker Leucine‐rich repeat‐containing G‐protein coupled receptor 5 (LGR5) has been described in GBM, but its functional role not conclusively elucidated. Here, we have investigated LGR5 a large repository patient‐derived GBM (GSC) cultures. The consequences overexpression or depletion analyzed using vitro vivo methods, showed that, among those with highest expression ( high ), there were two phenotypically distinct groups: one that was dependent on for properties another unaffected by changes expression. LGR5‐responding cultures could be identified their significantly higher self‐renewal capacity as measured extreme limiting dilution assay (ELDA), these ‐ELDA also more invasive compared to low This alone would strict responsiveness. In search additional biomarkers, LPAR4 , CCND2 OLIG2 upregulated LGR5‐responsive GSC cultures, found together radiation drug response. Overall, show regulates phenotype subset supports potential biomarker. Copyright © 2018 Pathological Society Great Britain Ireland. Published John Wiley & Sons, Ltd.

Language: Английский

Citations

23
A novel Foxp3-related immune prognostic signature for glioblastoma multiforme based on immunogenomic profiling DOI Creative Commons
Xiaoyu Guo, Guanhua Zhang, Zhenning Wang

et al.

Aging, Journal Year: 2021, Volume and Issue: 13(3), P. 3501 - 3517

Published: Jan. 10, 2021

Foxp3+ regulatory T cells (Treg) play an important part in the glioma immunosuppressive microenvironment. This study analyzed effect of Foxsp3 on immune microenvironment and constructed a Foxp3-related prognostic signature (IPS)for predicting prognosis glioblastoma multiforme (GBM). Immunohistochemistry (IHC) staining for Foxp3 was performed 72 high-grade specimens. RNA-seq data from 152 GBM samples were obtained The Cancer Genome Atlas database (TCGA) divided into two groups, High (Foxp3_H) Low (Foxp3_L), based expression. We systematically influence Least Absolute Shrinkage Selection Operator (LASSO) Cox analysis conducted immune-related genes that differentially expressed between Foxp3_H Foxp3_L patients. found differential expression tissues. presence significantly associated with poor OS. From four-gene IPS developed, patients stratified low-risk high-risk groups both training set validation sets. Furthermore, we developed novel nomogram to evaluate overall survival offers innovative insights these findings contribute individualized treatment improvement

Language: Английский

Citations

13
The oncogenic role of LGR6 overexpression induced by aberrant Wnt/β‐catenin signaling in lung cancer DOI Creative Commons
Noriaki Sunaga, Kyoichi Kaira, Kimihiro Shimizu

et al.

Thoracic Cancer, Journal Year: 2023, Volume and Issue: 15(2), P. 131 - 141

Published: Nov. 28, 2023

Abstract Background Molecular abnormalities in the Wnt/β‐catenin pathway confer malignant phenotypes lung cancer. Previously, we identified association of leucine‐rich repeat‐containing G protein‐coupled receptor 6 (LGR6) with oncogenic Wnt signaling, and its downregulation upon β‐catenin knockdown non‐small cell cancer (NSCLC) cells carrying CTNNB1 mutations. The aim this study was to explore mechanisms underlying accompanying phenotypes. Methods LGR6 expression lines surgical specimens analyzed using quantitative RT‐PCR immunohistochemistry. Cell growth assessed colony formation assay. Additionally, mRNA sequencing performed compare profiles subjected different treatments. Results overexpressed small (SCLC) NSCLC lines, including ‐mutated HCC15 A427. In both inhibited growth. upregulated spheroids compared adherent cultures A427 cells, suggesting that participates acquisition stem properties. Immunohistochemical analysis revealed protein predominantly SCLCs, large neuroendocrine carcinomas, adenocarcinomas, wherein overexpression associated vascular invasion, wild‐type EGFR genotype, an unfavorable prognosis. Integrated or without LGR6‐related pathways genes development stemness Conclusions Our findings highlight roles induced by aberrant signaling

Language: Английский

Citations

4
LGR6 is a prognostic biomarker for less differentiated tumors in lymph nodes of colon cancer patients DOI Creative Commons

Hagar Alaa Eldin Eltorky,

Manar AbdelMageed, Hager Tarek H. Ismail

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: April 23, 2024

Introduction The aim was to investigate whether the stem cell marker LGR6 has prognostic value in colon cancer, alone or combination with biomarkers CEA and CXCL16. Methods mRNA levels were determined 370 half lymph nodes of 121 cancer patients. Ability predict relapse after curative surgery estimated by Kaplan-Meier survival model Cox regression analyses. Results Patients high [LGR6(+)] had a decreased mean time 11 months at 5-year follow-up 47 12-year follow-up, respectively, hazard ratios 3.2 2.8. analysis added CXCL16 analysis. In poor prognosis groups CEA(+) CXCL16(+), further division achieved LGR6(+) patients very prognosis. also identified small number CEA(-), TNM stage I who relapsed suggesting origin these tumors. LGR5 correlated strongly IV but not II patients, that markers are differentially regulated. Conclusion This study highlights as useful biomarker independently CEA, identifying different risk groups.

Language: Английский

Citations

1
Analysis of multi-omics differences in left-side and right-side colon cancer DOI Creative Commons
Yanyi Huang,

Jinzhong Duanmu,

Yushu Liu

et al.

PeerJ, Journal Year: 2021, Volume and Issue: 9, P. e11433 - e11433

Published: May 12, 2021

Colon cancer is one of the most common tumors in digestive tract. Studies left-side colon (LCC) and right-side (RCC) show that these two subtypes have different prognoses, outcomes, clinical responses to chemotherapy. Therefore, a better understanding importance classifications anatomic needed.We collected patients' transcriptome data, information, somatic mutation data from Cancer Genome Atlas (TCGA) database portal. The were taken 390 patients (172 LCC samples 218 RCC samples); included 142 187 samples. We compared expression prognostic differences by conducting multi-omics analysis each using characteristics, immune microenvironment, transcriptomic differences, differences. signatures was validated internal testing set, complete external set (GSE39582). also verified independent value signature.The results our characteristic showed had significantly worse prognosis than LCC. microenvironment infiltration more differential gene there 360 differentially expressed genes, with upregulated genes RCC. frequency generally higher BRAF KRAS mutations dominant RCC, they strong mutual exclusion APC, while APC This suggests molecular mechanisms differed. 4-mRNA 6-mRNA respectively, highly predictive may be used as factors.The classification great significance for early diagnosis risk assessment. Our study provides directions individualized treatment left right cancer.

Language: Английский

Citations

9
The possibilities of LOXL4 as a prognostic marker for carcinomas DOI
Jiaming Wang, Chaojian Chen, Jiayi Huang

et al.

Amino Acids, Journal Year: 2023, Volume and Issue: 55(11), P. 1519 - 1529

Published: Oct. 9, 2023

Language: Английский

Citations

3
Inhibition of the long non‐coding RNA UNC5B‐AS1/miR‐4455/RSPO4 axis reduces cervical cancer growth in vitro and in vivo DOI
Jian Fu, Yuanyuan Zhang, Min Wang

et al.

The Journal of Gene Medicine, Journal Year: 2021, Volume and Issue: 23(12)

Published: Aug. 5, 2021

Long non-coding RNAs (lncRNAs) are significant regulatory factors for the initiation and development of numerous malignant tumors, including cervical cancer (CC). The expression lncRNA unc-5 netrin receptor B antisense RNA 1 (UNC5B-AS1, also known as UASR1) is up-regulated in tissues squamous cell carcinoma endocervical adenocarcinoma compared to normal based on GEPIA database. In present study, we explored functions UNC5B-AS1 its underlying mechanism with respect CC development.A real-time quantitative polymerase chain reaction was applied detection cells. Cell counting kit-8, colony formation transwell assays, well western blot flow cytometry analyses, were employed detect biological effects knockdown phenotypes cells vitro. addition, combination between microRNA-4455 (miR-4455) or R-spondin 4 (RSPO4) by immunoprecipitation, luciferase reporter pulldown assays. A tumor xenograft nude mice model established explore effect depletion miR-4455 overexpression growth.UNC5B-AS1 inhibits proliferation, migration invasion promotes apoptosis. Mechanistically, binds up-regulate RSPO4 expression. targeted negatively regulated vivo assays revealed that growth regulating expression.Inhibition UNC5B-AS1/miR-4455/RSPO4 reduces both vitro vivo, furnishing new insights into molecular studies development.

Language: Английский

Citations

7
Epithelial stem cell marker LGR6 expression identifies a low-risk subgroup in human papillomavirus positive oropharyngeal squamous cell carcinoma DOI
Bernhard J. Jank,

Lorenz Kadletz,

Daniela Dunkler

et al.

Oral Oncology, Journal Year: 2020, Volume and Issue: 105, P. 104657 - 104657

Published: March 31, 2020

Language: Английский

Citations

4