GNRH1 and LTB4R might be novel immune-related prognostic biomarkers in clear cell renal cell carcinoma (ccRCC)

Wu, Hua-Hui; Yan, Xin; Zhao, Chen; Du, Guo-Wei; Bai, Xiaojie; Tuoheti, Kurerban; Liu, Tong-Zu

doi:10.1186/s12935-021-02052-1

Cited by 11 publications

(9 citation statements)

References 32 publications

(34 reference statements)

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“…CSNK1E positively regulated the expression of differentially expressed immune genes related to survival such as AGER, GNRH1, SHC1, IRF9, TNFRSF25, LMBR1L, LTB4R, and LTB4R2. A recent study reported that AGER, GNRH1, SHC1, IRF9, and LTB4R could be used as prognostic factors of KIRC [ 29 , 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Effects and Prognostic Values of Circadian Genes CSNK1E/GNA11/KLF9/THRAP3 in Kidney Renal Clear Cell Carcinoma via a Comprehensive Analysis

Wang

et al. 2022

Bioengineering

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Kidney renal clear cell carcinoma (KIRC) is one of the most prevalent and deadly types of renal cancer in adults. Recent research has identified circadian genes as being involved in the development and progression of KIRC by altering their expression. This study aimed to identify circadian genes that are differentially expressed in KIRC and assess their role in KIRC progression. In KIRC, there were 553 differentially expressed rhythm genes (DERGs), with 300 up-regulated and 253 down-regulated DERGs. Functional enrichment analyses showed that DERGs were greatly enriched in the circadian rhythm and immune response pathways. Survival analyses indicated that higher expression levels of CSNK1E were related to shorter overall survival of KIRC patients, whereas lower expression levels of GNA11, KLF9, and THRAP3 were associated with shorter overall survival of KIRC patients. Through cell assay verification, the mRNA level of CSNK1E was significantly up-regulated, whereas the mRNA levels of GNA11, KLF9, and THRAP3 were dramatically down-regulated in KIRC cells, which were consistent with the bioinformatics analysis of KIRC patient samples. Age, grade, stage, TM classification, and CSNK1E expression were all shown to be high-risk variables, whereas GNA11, KLF9, and THRAP3 expression were found to be low-risk factors in univariate Cox analyses. Multivariate Cox analyses showed that CSNK1E and KLF9 were also independently related to overall survival. Immune infiltration analysis indicated that the proportion of immune cells varied greatly between KIRC tissues and normal tissue, whereas CSNK1E, GNA11, KLF9, and THRAP3 expression levels were substantially linked with the infiltration abundance of immune cells and immunological biomarkers. Moreover, interaction networks between CSNK1E/GNA11/KLF9/THRAP3 and immune genes were constructed to explore the stream connections. The findings could help us better understand the molecular mechanisms of KIRC progression, and CSNK1E/GNA11/KLF9/THRAP3 might be used as molecular targets for chronotherapy in KIRC patients in the near future.

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Section: Discussionmentioning

confidence: 99%

Effects and Prognostic Values of Circadian Genes CSNK1E/GNA11/KLF9/THRAP3 in Kidney Renal Clear Cell Carcinoma via a Comprehensive Analysis

Wang

et al. 2022

Bioengineering

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“…Many studies have reported that immune checkpoint blockade (ICB) therapy and combination regimens significantly improve survival in ccRCC patients [ 30 , 31 ]. Therefore, based on our previous studies [ 12 ], we further investigated LTB4R’s biological functions and mechanisms in the development of renal clear cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…The combination of leukotriene B4 receptor 1 (LTB4R) with LTB4 to activate leukocytes and prolong their survival as IAGs is significant in acute inflammatory responses [ 11 , 12 , 13 ]. BLT1 (LTB4R) is also an attractive drug target for allergic airway inflammation, inflammatory arthritis, atherosclerosis, and psoriasis [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

LTB4R Promotes the Occurrence and Progression of Clear Cell Renal Cell Carcinoma (ccRCC) by Regulating the AKT/mTOR Signaling Pathway

Zhang

Yan

et al. 2022

Cells

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ccRCC is highly immunogenic, yet its underlying immune-related molecular mechanisms are unknown. Leukotriene B4 Receptor 1 (LTB4R), a novel immune-related gene associated in our previous research with the prognosis of ccRCC patients, has been found in many cancers; however, its potential mechanism in renal clear carcinoma is unclear. This study was conducted to investigate LTB4R’s action mechanism in renal clear cell carcinoma. First, a CCK8 assay was performed to verify LTB4R’s effect on the proliferation viability of renal clear cell carcinoma cells. Scratch and transwell assays verified LTB4R’s effect on the migration and invasion ability of renal clear cell carcinoma cells. Flow cytometry validated LTB4R’s effect on renal clear cell carcinoma cells’ apoptosis and cell cycle. A Western blot assay was conducted to further investigate LTB4R’s effect on apoptosis, cell cycle, EMT process, and AKT/mTOR signaling pathway in renal clear cell carcinoma at the protein level. In vitro experiments showed that LTB4R knockdown inhibited the proliferation, migration, and invasion of renal clear cell carcinoma cells and promoted their apoptosis, whereas LTB4R overexpression promoted the proliferation, migration, and invasion of renal clear cell carcinoma cells and inhibited their apoptosis. In addition, we found that LTB4R regulated the proliferation and apoptosis of renal clear cell carcinoma cells by regulating the AKT/mTOR signaling pathway’s phosphorylation process. Furthermore, we verified some of these results using bioinformatic analysis. LTB4R plays an oncogenic role in renal clear cell carcinoma; it is expected to be a molecular target for renal clear cell carcinoma treatment and a predictive biomarker for prognosis.

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“…Microslaw et al [ 17 ] demonstrated that the expression levels of chorionic gonadotropin beta subunit and GnRH1 in the blood of cancer patients might be valuable in indicating tumor metastasis and spread. Wu et al [ 18 ] demonstrated that GnRH1 and LTB4R are prognostic biomarkers for patients with ccRCC.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of immune-related prognostic genes and immunotherapy in renal clear cell carcinoma

et al. 2022

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Clear cell renal cell carcinoma (ccRCC) is an immunogenic tumor, and investigating the immunorelated genes is essential. To investigate the immunoprognostic genes of ccRCC, we analyzed the data assimilated from a public database (The Cancer Genome Atlas (TCGA) database and the gene expression omnibus (GEO) database) using bioinformatics. Then, an immunoprognosis model was constructed to identify four hub genes with moderate predictive values for the prognosis of ccRCC patients. These four genes were associated with the prognosis of ccRCC patients based on Oncomine and Gena Expression Profiling Interactive Analysis (GEPIA) databases. The correlation analysis between the immune infiltrate, immune checkpoints, and immunotherapy and this immunoprognosis model showed that immune infiltration could predict the immunotherapy effects. We also conducted a quantitative real-time polymerase chain reaction analysis and found that the expressions of three hub genes were associated with tumor progression (P<0.1). In conclusion, four genes that may serve as potential biomarkers in ccRCC were identified with respect to prognosis.

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GNRH1 and LTB4R might be novel immune-related prognostic biomarkers in clear cell renal cell carcinoma (ccRCC)

Cited by 11 publications

References 32 publications

Effects and Prognostic Values of Circadian Genes CSNK1E/GNA11/KLF9/THRAP3 in Kidney Renal Clear Cell Carcinoma via a Comprehensive Analysis

Effects and Prognostic Values of Circadian Genes CSNK1E/GNA11/KLF9/THRAP3 in Kidney Renal Clear Cell Carcinoma via a Comprehensive Analysis

LTB4R Promotes the Occurrence and Progression of Clear Cell Renal Cell Carcinoma (ccRCC) by Regulating the AKT/mTOR Signaling Pathway

Bioinformatics analysis of immune-related prognostic genes and immunotherapy in renal clear cell carcinoma

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