Timing of mTORI usage and outcomes in kidney transplant recipients

Lim, Lee‐Moay; Kung, Lan-Fang; Kuo, Mei‐Chuan; Huang, A-Mei; Kuo, Hung-Tien

doi:10.7150/ijms.53655

Cited by 5 publications

(6 citation statements)

References 34 publications

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“…First, this was a retrospective study with a limited sample size. Second, due to limitations in sample collection, all the patients in our study groups were female; nonetheless, this is consistent with the finding that most UCKT individuals in the Taiwanese population are female [ 11 , 82 ]. Additional studies with larger sample sizes are required to achieve conclusive results.…”

Section: Discussionsupporting

confidence: 85%

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Whole-exome sequencing identified mutational profiles of urothelial carcinoma post kidney transplantation

et al. 2022

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Kidney transplantation is a lifesaving option for patients with end-stage kidney disease. In Taiwan, urothelial carcinoma (UC) is the most common de novo cancer after kidney transplantation (KT). UC has a greater degree of molecular heterogeneity than do other solid tumors. Few studies have explored genomic alterations in UC after KT. We performed whole-exome sequencing to compare the genetic alterations in UC developed after kidney transplantation (UCKT) and in UC in patients on hemodialysis (UCHD). After mapping and variant calling, 18,733 and 11,093 variants were identified in patients with UCKT and UCHD, respectively. We excluded known single-nucleotide polymorphisms (SNPs) and retained genes that were annotated in the Catalogue of Somatic Mutations in Cancer (COSMIC), in the Integrative Onco Genomic cancer mutations browser (IntOGen), and in the Cancer Genome Atlas (TCGA) database of genes associated with bladder cancer. A total of 14 UCKT-specific genes with SNPs identified in more than two patients were included in further analyses. The single-base substitution (SBS) profile and signatures showed a relative high T > A pattern compared to COMSIC UC mutations. Ingenuity pathway analysis was used to explore the connections among these genes. GNAQ, IKZF1, and NTRK3 were identified as potentially involved in the signaling network of UCKT. The genetic analysis of posttransplant malignancies may elucidate a fundamental aspect of the molecular pathogenesis of UCKT.

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Section: Discussionsupporting

confidence: 85%

“…The standardized incidence ratio of urinary tract malignancies (among which bladder cancer was the most common) among recipients of a kidney transplant was 10.93 (95% CI, 9.20–12.99) [ 10 ]. Furthermore, in our previous single-center retrospective study, the most common PTMs were UC and hepatocellular carcinoma [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Whole-exome sequencing identified mutational profiles of urothelial carcinoma post kidney transplantation

et al. 2022

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“…First, this was a retrospective study with a limited sample size. Second, due to limitations in sample collection, all the patients in our study groups were female; nonetheless, this is consistent with the finding that most UCKT individuals in the Taiwanese population are female [11,60]. Additional studies with larger sample sizes are required to achieve conclusive results.…”

Section: Discussionsupporting

confidence: 83%

“…10 Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. 11 Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 12 Ph.D.…”

Section: Abbreviationsmentioning

confidence: 99%

Whole-Exome Sequencing Identified Mutational Profiles of Urothelial Carcinoma post Kidney Transplantation

Lim,

Chung,

Hwang

et al. 2022

Preprint

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Background: Kidney transplantation is a lifesaving option of selected patients with end-stage kidney disease (ESKD). Urothelial carcinoma (UC) is the most common de novo cancer after kidney transplantation in Taiwan. UC has the characteristics of high mutational burden and elevated degree of molecular heterogeneity compared with other solid tumors. However, there are limited research exploring the genomic alterations in UC after kidney transplantation. Methods: In this study, we performed whole exome sequencing (WES) to compare the genetic alterations between UC developed after kidney transplantation (UCKT) and UC from hemodialysis patients (UCHD). After mapping and variant calling, a total of 18,733 and 11,093 mutations were identified from UCKT and UCHD patients, respectively. We first excluded known SNPs and then retained genes that were annotated in Cosmic, Intogen, and TCGA bladder databases for onco-driver genes. Seventeen UCKT unique genes with recurrent SNPs in more than two patients were subjected for further analysis. IPA pathway analysis was used to explore the interconnections among these genes. Results: 17 novel mutations of BTK, CARD11, ELL, FNBP1, GNAQ, HOXD13, IKZF1, MAX, MLLT10, NTRK3, PAX5, SEPTIN6, SEPTIN9, SH3GL1, SLC34A2, TAL1 , and TRAF7 were identified UCKT groups, and none of the genes had been reported in the genomes of patients with UC. Among the affected genes, GNAQ, IKZF1, and NTRK3 were potentially involved in the signaling network of UCKT. Conclusion : Our findings provide information for understanding the mutational landscape of UC developed after kidney transplantation, and a gene list that may be of great importance in related molecular mechanisms. Genetic analysis in malignancy after transplantation may help to identify high risk patients in post-transplant care and also illuminate a fundamental aspect of the molecular pathogenesis of post-transplantation UC.

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“…3,29 Our previous study demonstrated that UC was most common renal pelvic or bladder malignancy observed following kidney transplants in Taiwan. 30 Increasing evidence from genomic studies has gradually revealed the molecular landscape of UTUC and identifying numerous gene alterations that are promising targets for gene therapies.…”

Section: Ntrk3 Expression Associated With Cellular Migration and Inva...mentioning

confidence: 99%

NTRK3 exhibits a pro‐oncogenic function in upper tract urothelial carcinomas

Lim,

Lee,

Lin

et al. 2024

The Kaohsiung J of Med Scie

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Neurotrophic receptor tyrosine kinase 3 (NTRK3) has pleiotropic functions: it acts not only as an oncogene in breast and gastric cancers but also as a dependence receptor in tumor suppressor genes in colon cancer and neuroblastomas. However, the role of NTRK3 in upper tract urothelial carcinoma (UTUC) is not well documented. This study investigated the association between NTRK3 expression and outcomes in UTUC patients and validated the results in tests on UTUC cell lines. A total of 118 UTUC cancer tissue samples were examined to evaluate the expression of NTRK3. Survival curves were generated using Kaplan–Meier estimates, and Cox regression models were used for investigating survival outcomes. Higher NTRK3 expression was correlated with worse progression‐free survival, cancer‐specific survival, and overall survival. Moreover, the results of an Ingenuity Pathway Analysis suggested that NTRK3 may interact with the PI3K‐AKT‐mTOR signaling pathway to promote cancer. NTRK3 downregulation in BFTC909 cells through shRNA reduced cellular migration, invasion, and activity in the AKT‐mTOR pathway. Furthermore, the overexpression of NTRK3 in UM‐UC‐14 cells promoted AKT‐mTOR pathway activity, cellular migration, and cell invasion. From these observations, we concluded that NTRK3 may contribute to aggressive behaviors in UTUC by facilitating cell migration and invasion through its interaction with the AKT‐mTOR pathway and the expression of NTRK3 is a potential predictor of clinical outcomes in cases of UTUC.

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Timing of mTORI usage and outcomes in kidney transplant recipients

Cited by 5 publications

References 34 publications

Whole-exome sequencing identified mutational profiles of urothelial carcinoma post kidney transplantation

Whole-exome sequencing identified mutational profiles of urothelial carcinoma post kidney transplantation

Whole-Exome Sequencing Identified Mutational Profiles of Urothelial Carcinoma post Kidney Transplantation

NTRK3 exhibits a pro‐oncogenic function in upper tract urothelial carcinomas

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