Clinical significance of reduced GPRC5A expression in surgically resected non‑small cell lung cancer

Jin, Er; Wang, Wenzhe; Fang, Man; Wang, Wei; Xie, Rong; Zhou, Hong; Ye, Jian; Xu, Ruochen; Ma, Shenglin

doi:10.3892/ol.2018.9537

Cited by 6 publications

(6 citation statements)

References 22 publications

(28 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This gene encodes G protein-coupled receptors involved in signaling pathways in development, cellular growth, and epithelial cell differentiation. GPRC5A can block EGFR expression and activation 90 . GPRC5A is expressed in lung type I and type II epithelial cells constitutively 91 .…”

Section: Discussionmentioning

confidence: 99%

Derangement of cell cycle markers in peripheral blood mononuclear cells of asthmatic patients as a reliable biomarker for asthma control

Hachim

Elemam

Ramakrishnan

et al. 2021

Sci Rep

View full text Add to dashboard Cite

In asthma, most of the identified biomarkers pertain to the Th2 phenotype and no known biomarkers have been verified for severe asthmatics. Therefore, identifying biomarkers using the integrative phenotype-genotype approach in severe asthma is needed. The study aims to identify novel biomarkers as genes or pathways representing the core drivers in asthma development, progression to the severe form, resistance to therapy, and tissue remodeling regardless of the sample cells or tissues examined. Comprehensive reanalysis of publicly available transcriptomic data that later was validated in vitro, and locally recruited patients were used to decipher the molecular basis of asthma. Our in-silicoanalysis revealed a total of 10 genes (GPRC5A, SFN, ABCA1, KRT8, TOP2A, SERPINE1, ANLN, MKI67, NEK2, and RRM2) related to cell cycle and proliferation to be deranged in the severe asthmatic bronchial epithelium and fibroblasts compared to their healthy counterparts. In vitro, RT qPCR results showed that (SERPINE1 and RRM2) were upregulated in severe asthmatic bronchial epithelium and fibroblasts, (SFN, ABCA1, TOP2A, SERPINE1, MKI67, and NEK2) were upregulated in asthmatic bronchial epithelium while (GPRC5A and KRT8) were upregulated only in asthmatic bronchial fibroblasts. Furthermore, MKI76, RRM2, and TOP2A were upregulated in Th2 high epithelium while GPRC5A, SFN, ABCA1 were upregulated in the blood of asthmatic patients. SFN, ABCA1 were higher, while MKI67 was lower in severe asthmatic with wheeze compared to nonasthmatics with wheezes. SERPINE1 and GPRC5A were downregulated in the blood of eosinophilic asthmatics, while RRM2 was upregulated in an acute attack of asthma. Validation of the gene expression in PBMC of locally recruited asthma patients showed that SERPINE1, GPRC5A, SFN, ABCA1, MKI67, and RRM2 were downregulated in severe uncontrolled asthma. We have identified a set of biologically crucial genes to the homeostasis of the lung and in asthma development and progression. This study can help us further understand the complex interplay between the transcriptomic data and the external factors which may deviate our understanding of asthma heterogeneity.

show abstract

Section: Discussionmentioning

confidence: 99%

Derangement of cell cycle markers in peripheral blood mononuclear cells of asthmatic patients as a reliable biomarker for asthma control

Hachim

Elemam

Ramakrishnan

et al. 2021

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Finally, 15 studies comprising a total of 3349 patients were included in the meta-analysis. The types of cancer in the studies included: colorectal cancer [ 22 , 23 ], pancreatic cancer [ 24 – 27 ], gastric cancer [ 28 , 29 ], esophageal cancer [ 30 ], prostate cancer [ 31 ], hepatocellular cancer [ 32 ], head and neck squamous cell carcinoma [ 33 ], lung cancer [ 34 ], and ovarian cancer [ 35 ]. The characteristics of the enrolled articles are summarized in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

Prognostic and clinicopathological significance of GPRC5A in various cancers: A systematic review and meta-analysis

2021

View full text Add to dashboard Cite

Background GPRC5A is associated with various cancer initiation and progression. Controversial findings have been reported about GPRC5A prognostic characteristics, and no meta-analysis has been conducted to assess the relationship between GPRC5A and cancer prognosis. Therefore, the objective of this meta-analysis is to evaluate the overall prognostic effectiveness of GPRC5A. Methods We first conducted a systematic search in the PubMed, Embase, Web of Science, CNKI, Cochrane, and WangFang databases. The hazard ratio (HR) and odds ratios (OR) with 95% CI were then pooled to assess the associations between GPRC5A expression and overall survival (OS), disease-free survival (DFS), event-free survival (EFS), and clinicopathological characteristics. Chi-squared test and I2 statistics were completed to evaluate the heterogeneity in our study. A random‐effects model was used when significant heterogeneity existed (I2>50% and p<0.05); otherwise, we chose the fixed-effect model. Subgroup analysis was stratified by tumor type, region, HR obtained measurements, and sample capacity to explore the source of heterogeneity. Results In total, 15 studies with 624 patients met inclusion criteria of this study. Our results showed that higher expression of GPRC5A is associated with worse OS (HR:1.69 95%CI: 1.20–2.38 I2 = 75.6% p = 0.000), as well as worse EFS (HR:1.45 95%CI: 1.02–1.95 I2 = 0.0% p = 0.354). Subgroup analysis indicated that tumor type might be the source of high heterogeneity. Additionally, cancer patients with enhanced GPRC5A expression were more likely to lymph node metastasis (OR:1.95, 95%CI 1.33–2.86, I2 = 43.9%, p = 0.129) and advanced tumor stage (OR: 1.83, 95%CI 1.15–2.92, I2 = 61.3%, p = 0.035), but not associated with age, sex, differentiation, and distant metastasis. Conclusion GPRC5A can be a promising candidate for predicting medical outcomes and used for accurate diagnosis, prognosis prediction for patients with cancer; however, the predictive value of GPRC5A varies significantly according to cancer type. Further studies for this mechanism will be necessary to reveal novel insights into application of GPRC5A in cancers.

show abstract

“…GPRC5a is a potential therapeutic target and biomarker in several solid tumors including prostate cancer, lung cancer or colon cancer 45,46 . It has been identified in a differential gene expression analysis comparing T1 and T3 ccRCC stages 47 .…”

Section: Discussionmentioning

confidence: 99%

“…Mechanistically, GPRC5A acts via the Hippo pathway effector YAP 48 . However, in non-small cell lung carcinoma (NSCLC), GPRC5A is expressed as much lower levels than in the corresponding noncancerous tissues and was associated to a worse prognosis 46 . Thus, the role of GPRC5A seems context-dependent and either associated with a pro-tumor or anti-tumor context.…”

Section: Discussionmentioning

confidence: 99%

A multi-layered systems approach for renal cell carcinoma

Rudewicz

Souleyreau

et al. 2020

Preprint

View full text Add to dashboard Cite

Acknowledgments:This work was supported by grants from the PlanCancer («Systems Biology of Renal Cell Carcinoma using an Experimental RCC model» (C18005GS, SystemsRCC)) and from the university Bordeaux (G2P project) to AB. LC and AE were supported by post-doctoral fellowships from the Region "Nouvelle Aquitaine". The Crispr/cas9 construct was gratefully provided by Michel Tremblay (Goodman Cancer Center, McGill, University). The authors would like to thank the lentiviral production plateform Vect'UB for EGFP lentivirus, the "service commun des animaleries" for animal production and housing, and the Bordeaux Imaging Center (BIC). 2 AbstractIn order to discover molecular pathways and players in renal cancer development and metastasis, we developed a mouse model to generate sequentially more aggressive and specialized cell lines. Multiple cell lines for primary tumor growth, survival in the blood circulation and lung metastasis or metastatic spread from the primary tumor were generated and analyzed using a multi-layered approach which includes large-scale transcriptome, genome and methylome analyses. Transcriptome and methylome analyses demonstrated distinct clustering in three different groups. Remarkably, DNA sequencing did not show significant genomic variations in the different groups which indicates absence of clonal selection during the in vivo amplification process. Transcriptome analysis revealed several markers and signatures of tumor aggressiveness which were validated, at the mRNA and protein level, in patient cohorts from TCGA, local biobanks and clinical trials. This also includes soluble markers. In particular, SAA2 and CFB were highly predictive for survival and tumor progression. Methylome analysis of full-length DNA allowed clustering of the same groups and revealed clinically predictive signatures. We also uncovered IL34 as a key regulator of renal cell carcinoma (RCC) progression which was also functionally validated in vivo, and a mathematical model of IL34-dependent primary tumor growth and metastasis development was provided. These results indicate that such multilayered analysis in a RCC animal model leads to meaningful results that are of translational significance. 3

show abstract

Clinical significance of reduced GPRC5A expression in surgically resected non‑small cell lung cancer

Cited by 6 publications

References 22 publications

Derangement of cell cycle markers in peripheral blood mononuclear cells of asthmatic patients as a reliable biomarker for asthma control

Derangement of cell cycle markers in peripheral blood mononuclear cells of asthmatic patients as a reliable biomarker for asthma control

Prognostic and clinicopathological significance of GPRC5A in various cancers: A systematic review and meta-analysis

A multi-layered systems approach for renal cell carcinoma

Contact Info

Product

Resources

About