LIMCH1 as a New Potential Metastasis Predictor in Breast Cancer

Alifanov, V.V.; Таширева, Л. А.; Zavyalova, М. V.; Перельмутер, В. М.

doi:10.31557/apjcp.2022.23.11.3947

Cited by 6 publications

(3 citation statements)

References 11 publications

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“…Studies showed that it played an important role in ovarian cancer by affecting cell proliferation and tumour sensitivity to therapy ( 34 ). Furthermore, the ARHGEF19 gene located on chromosome 2 and the LIMCH1 gene located on chromosome 13, within each of which we found one SNP ( TIGRP2P33447_rs8841788 and TIGRP2P176993_rs9197628 , respectively), were associated with an increased risk of breast cancer ( 3 , 30 ).…”

Section: Discussionmentioning

confidence: 84%

Identification of SNP markers for canine mammary gland tumours in females based on a genome-wide association study – preliminary results

Mucha

Nowak

Dzimira

et al. 2023

Journal of Veterinary Research

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Introduction The development of genetic research over recent decades has enabled the discovery of new genetic markers, such as single nucleotide polymorphisms (SNPs). This, as well as the full sequencing of the dog genome, has enabled genome-wide association studies (GWAS) to be used in the search for genetic causes of canine mammary tumours (CMTs). Material and Methods Genotypic data containing 175,000 SNPs, which had been obtained using the Illumina CanineHD BeadChip microarray technique, were available for analysis in this study. The data concerned 118 bitches, including 36 animals with CMT, representing various breeds and age groups. Statistical analysis was performed in two steps: quality control of genotyping data and genome-wide association analysis based on dominant, recessive, overdominant, codominant, and log-additive models with the single SNP effects. Results A total of 40 different SNPs significantly associated with CMT appearance were detected. Moreover, twelve SNPs showed statistical significance in more than one model. Of all the significant SNPs, two, namely BICF2G630136001 in the overdominant model and TIGRP2P107898_rs9044787 in the log-additive model, reached the 5−8 significance level. The other SNPs were significant to a 1−5 level. Conclusion In the group of SNPs indicated as significant in the GWAS analysis, several transpired to be localised within genes that may play an important role in CMT.

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Section: Discussionmentioning

confidence: 84%

Identification of SNP markers for canine mammary gland tumours in females based on a genome-wide association study – preliminary results

Mucha

Nowak

Dzimira

et al. 2023

Journal of Veterinary Research

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“…Of these genes, PTK7, KLK6 and LIMCH1 have interesting links with breast cancer; PTK7 is a catalytically inactive receptor tyrosine kinase in the Wnt signalling pathway, and a PTK7 targeted antibody-drug conjugate has been shown to reduce tumour-initiating cells 52 . Both KLK6 and LIMCH1 expression has been linked to clinical outcome of breast cancer patients 53,54 The signi cant associations observed between DARPP-32 and its downstream targets DKK1 and GRB7 and patient survival, underscore their importance in breast cancer. By using an approach that combines patient and cell line transcriptomics we have identi ed a number of common genes that provides an insight into the molecular mechanisms underlying differential breast cancer prognosis and highlights potential targets for therapeutic intervention.…”

Section: Discussionmentioning

confidence: 99%

Unravelling transcriptomic complexity in breast cancer through modulation of DARPP-32 expression and signalling pathways

Saidy

Vasan

Durant

et al. 2023

Preprint

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DARPP-32 is a key regulator of protein-phosphatase-1 (PP-1) and protein kinase A (PKA), with its function dependent upon its phosphorylation state. We previously identified DKK1 and GRB7 as genes with linked expression using Artificial Neural Network (ANN) analysis; here, we determine protein expression in a large cohort of early-stage breast cancer patients. Low levels of DARPP-32 Threonine-34 phosphorylation and DKK1 expression were significantly associated with poor patient prognosis, while low levels of GRB7 expression were linked to better survival outcomes. To gain insight into mechanisms underlying these associations, we analysed the transcriptome of T47D breast cancer cells following DARPP-32 knockdown. We identified 202 differentially expressed transcripts and observed that some overlapped with genes implicated in the ANN analysis, including PTK7, TRAF5, and KLK6, amongst others. Furthermore, we found that treatment of DARPP-32 knockdown cells with 17β-estradiol or PKA inhibitor fragment (6–22) amide led to the differential expression of 193 and 181 transcripts respectively. These results underscore the importance of DARPP-32, a central molecular switch, and its downstream targets, DKK1 and GRB7 in breast cancer. The discovery of common genes identified by a combined patient/cell line transcriptomic approach provides insights into the molecular mechanisms underlying differential breast cancer prognosis and highlights potential targets for therapeutic intervention.

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“…Among these signature genes, SLC16A12 has been previously reported to have excellent effectiveness and clinical application value in ccRCC ( 23 ). There is an unfavorable association between LIMCH1 protein expression and distant metastasis-free survival in breast cancer ( 24 ). In addition, as well as being a component of exosomes, the GIPC2 paralog plays a key role in WNT signaling pathways associated with tumor progression and was shown to be robustly stimulating the adhesion, invasion, and migration of prostate cancer ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

Cuproptosis in ccRCC: key player in therapeutic and prognostic targets

Lv,

Li,

Yin

et al. 2023

Front. Oncol.

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BackgroundClassical biomarkers have been used to classify clear cell renal cell carcinoma (ccRCC) patients in a variety of ways, and emerging evidences have indicated that cuproptosis is closely related to mitochondrial metabolism, thereby accelerating the development and progression of ccRCC. Nevertheless, the specific relationship between cuproptosis and the prognosis and treatment of ccRCC remains unclear.MethodsWe comprehensively integrated several ccRCC patient datasets into a large cohort. Following that, we systematically analyzed multi-omics data to demonstrate the differences between two cuproptosis clusters.ResultsWe identified two cuproptosis clusters in ccRCC patients. Among the two clusters, cluster 1 patients showed favorable prognosis. We then confirmed the significant differences between the two clusters, including more typical cancer hallmarks were enriched in cluster 2 patients; cluster 2 patients were more susceptible to develop mutations and had a lower level of gistic score and mRNAsi. Importantly, both Tumor Immune Dysfunction and Exclusion analysis and subclass mapping algorithm showed that cuproptosis 1 patients were more susceptible to be responded to immunotherapy. In addition, a prognostic signature was successfully developed and also showed prominent predictive power in response to immunotherapy.ConclusionAs a result of our findings, we were able to classify ccRCC patients according to cuproptosis in a novel way. By constructing the cuproptosis clusters and developing the signature, patients with ccRCC could have a more accurate prognosis prediction and better immunotherapy options.

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LIMCH1 as a New Potential Metastasis Predictor in Breast Cancer

Cited by 6 publications

References 11 publications

Identification of SNP markers for canine mammary gland tumours in females based on a genome-wide association study – preliminary results

Identification of SNP markers for canine mammary gland tumours in females based on a genome-wide association study – preliminary results

Unravelling transcriptomic complexity in breast cancer through modulation of DARPP-32 expression and signalling pathways

Cuproptosis in ccRCC: key player in therapeutic and prognostic targets

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