Association of PTPRT Mutations with Cancer Metastasis in Multiple Cancer Types

Chen, Chao; Liu, Haozhen; Xu, Qumiao; Zhang, Xiuqing; Mu, Feng; Liu, Jixian

doi:10.1155/2022/9386477

Cited by 6 publications

(9 citation statements)

References 31 publications

(49 reference statements)

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“…PTPRT , a member of the protein tyrosine phosphatase (PTP) family, has been reported to be a tumor suppressor gene in BC and other cancers. 38-44 NCKAP5 , potentially functioning in microtubule bundle formation and microtubule depolymerization, is less studied, and polymorphisms in this gene are reported to be associated with the clinical outcome of gastric cancer patients in a recent study. 45 Overall, our study suggests different genetic factors controlling tumor onset, multiplicity, metastasis, as well as the site of metastasis.…”

Section: Discussionmentioning

confidence: 99%

A susceptibility gene signature for ERBB2-driven mammary tumor development and metastasis in Collaborative Cross mice with human translational value

Yang,

Wang,

Blanco-Gómez

et al. 2024

Preprint

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BackgroundDeeper insights into ERBB2-driven cancers are essential to develop novel treatment avenues for ERBB2+ breast cancers (BCs). We employed Collaborative Cross (CC) mouse model, along with human translational evaluation, to unearth genetic factors underpinning Erbb2-driven mammary tumor development and metastasis.Methods732 F1 hybrid female mice between FVB/N MMTV-Erbb2and 30 CC strains were monitored for mammary tumor phenotypes. GWAS pinpointed SNPs that influence various tumor phenotypes. Clinical value of a mouse tumor susceptibility gene signature (mTSGS) was evaluated using public datasets, encompassing TCGA, METABRIC and I-SPY2 cohorts. The predictive power of mTSGS for response to chemotherapy was validatedin vivousing genetically diverse MMTV-Erbb2mice.ResultsDistinct variances in tumor onset, multiplicity, and metastatic patterns were observed across CC strains. Besides lung metastasis, liver and kidney metastases emerged in specific CC strains. GWAS identified 1525 SNPs, 800 SNPs, 568 SNPs, and 23 SNPs significantly associated with tumor onset, multiplicity, lung metastasis, and liver metastasis, respectively. Multivariate analyses flagged SNPs in 20 genes independently tied to various tumor characteristics, designated as mTSGS. These 20 genes were transcriptionally altered in human BCs. We then established mTSGS scores (mTSGSS) based on their transcriptional levels. The mTSGSS showed prognostic values, superseding clinical factors and PAM50 molecular subtype across cohorts. Moreover, mTSGSS predicted pathological complete response (pCR) to six of thirteen treatment regimens, including chemotherapy only, in I-SPY2 study. Importantly, the predictive value of the mTSGSS for pCR stood independent of the MammaPrint score. The power of mTSGSS for predicting chemotherapy response was validated in anin vivoMMTV-Erbb2 model, showing that like findings in human patients, mouse tumors with low mTSGSS were most likely to respond to treatment.ConclusionOur investigation has unveiled many novel genes predisposing individuals to ERBB2-driven cancer. Translational findings indicate that mTSGSS holds promise as a biomarker to refine treatment strategies for BC patients.

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Section: Discussionmentioning

confidence: 99%

A susceptibility gene signature for ERBB2-driven mammary tumor development and metastasis in Collaborative Cross mice with human translational value

Yang,

Wang,

Blanco-Gómez

et al. 2024

Preprint

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“…PTPRT and ARHGEF4 were identi ed as hub genes in our research. PTPRT, known as a tumor suppressor gene, is implicated in regulating various cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation [40][41][42] . It has been shown to play important roles in promoting malignant cell proliferation in HCC patients harboring hepatitis B virus 40 .…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of hepatocellular carcinoma reveals disparate subtype of prognosis significance

Jiang,

Zhang

et al. 2024

Preprint

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Hepatocellular carcinoma (HCC) is a complex disease with various contributing factors. Most clinical biomarkers fall short in providing an accurate prognostic evaluation for HCC patients. This underscores the urgent need to gain insight into the role of key molecules in disease progression and to develop more dependable prognosis prediction models. Our study reported that molecular subtyping based on transcriptome profiling could serve as an independent predictor of HCC prognosis. The joint use of molecular subtyping and American Joint Committee on Cancer (AJCC) staging system was superior to each individual factor as a prognostic indicator. The multi-omics analysis revealed the activation of signal transduction, cytokines interaction, cell proliferation pathways in category A (CA) tumors, while organic compound metabolism pathways were enriched in category B (CB) tumors. These findings indicated significant and substantial molecular differences among prognostically relevant subtypes. This research highlighted the potential for widespread development and validation of molecular subtyping to improve clinical management of HCC patients. Through gaining a better understanding of the molecular variances among subtypes, such as different pathogenic pathways, this approach could guide more effective and tailored therapeutic strategies.

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“…The study of Zhu et al suggested that ARID1A mutations were related to the good prognosis of immune checkpoint inhibitors (ICI) therapy based on the pan-cancer population [ 59 ]. The study of Chen et al suggested that PTPRT mutation is associated with poor progression-free survival in pan-cancer and NSCLC [ 60 ]. Contrary to our results, the study of Zhang et al showed that melanoma patients with PTPRT mutations harbored a significantly elevated ICI response rate and a prolonged survival outcome, and in the NSCLC cohort, the favorable response and immunotherapy survival were also observed in PTPRT -mutated patients [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular profiling and prognostic biomarkers in chinese non-small cell lung cancer cohort

Shen¹,

Guo²,

Song³

et al. 2023

Diagn Pathol

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Introduction Comprehensive information about the genome analysis and its prognostic values of NSCLC patients in Chinese population are still needed. Patients A total of 117 Chinese patients with NSCLC were enrolled in this study. Tumor tissues or blood were collected and sequenced by targeted next-generation sequencing of 556 cancer related genes. The associations between clinical outcomes and clinical characteristics, TMB, mutated genes, treatment therapies were analyzed using Kaplan-Meier methods and further evaluated using multivariable Cox proportional hazards regression model. Results A total of 899 mutations were identified by targeted NGS. The most frequently mutations included EGFR (47%), TP53 (46%), KRAS (18%), LRP1B (12%) and SPTA1 (10%). Patients with mutant TP53, PREX2, ARID1A, PTPRT and PIK3CG had lower median overall survival (OS) than those patients with wild-type (P = 0.0056, P < 0.001, P < 0.0001, P < 0.0001 and P = 0.036, respectively). Using a multivariate Cox regression model, PREX2 (P < 0.001), ARID1A (P < 0.001) and PIK3CG (P = 0.04) were independent prognostic factors in NSCLC. In the patients received chemotherapy, squamous patients had a significantly longer median OS than adenocarcinoma patients (P = 0.011). In the patients received targeted therapy, adenocarcinoma patients had a significantly longer survival period than squamous patients (P = 0.01). Conclusions Our study provided comprehensive genomic alterations in a cohort of Chinese NSCLC. We also identified new prognostic biomarkers, which could provide potential clues for targeted therapies.

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Association of PTPRT Mutations with Cancer Metastasis in Multiple Cancer Types

Cited by 6 publications

References 31 publications

A susceptibility gene signature for ERBB2-driven mammary tumor development and metastasis in Collaborative Cross mice with human translational value

A susceptibility gene signature for ERBB2-driven mammary tumor development and metastasis in Collaborative Cross mice with human translational value

Integrated analysis of hepatocellular carcinoma reveals disparate subtype of prognosis significance

Molecular profiling and prognostic biomarkers in chinese non-small cell lung cancer cohort

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