PTPRT Could Be a Treatment Predictive and Prognostic Biomarker for Breast Cancer

Li, Lun; Xu, Feng; Xie, Pingfang; Yuan, Liqin; Zhou, Meirong

doi:10.1155/2021/3301402

Cited by 8 publications

(11 citation statements)

References 31 publications

(48 reference statements)

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“…This exploration revealed six miRNA: mRNA pairs when a higher expression of the miRNAs with positive coefficients intersected with downregulated genes in the high-risk group. Intriguingly, among these downregulated genes, CLEC10A and PTPRT have been demonstrated as poor prognostic factors when their expressions were reduced in breast cancer, suggesting a plausible negative regulatory mechanism of these miRNAs in our TRM signature [92,93]. Similarly, it reduced the expression of the TP63; a known suppressor of cell migration and metastasis and could lead to enhanced tumor invasion and migration [94].…”

Section: Discussionmentioning

confidence: 83%

An Eleven-microRNA Signature Related to Tumor-Associated Macrophages Predicts Prognosis of Breast Cancer

Jayasingam

Citartan

Zin

et al. 2022

IJMS

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The dysregulation of microRNAs (miRNAs) has been known to play important roles in tumor development and progression. However, the understanding of the involvement of miRNAs in regulating tumor-associated macrophages (TAMs) and how these TAM-related miRNAs (TRMs) modulate cancer progression is still in its infancy. This study aims to explore the prognostic value of TRMs in breast cancer via the construction of a novel TRM signature. Potential TRMs were identified from the literature, and their prognostic value was evaluated using 1063 cases in The Cancer Genome Atlas Breast Cancer database. The TRM signature was further validated in the external Gene Expression Omnibus GSE22220 dataset. Gene sets enrichment analyses were performed to gain insight into the biological functions of this TRM signature. An eleven-TRM signature consisting of mir-21, mir-24-2, mir-125a, mir-221, mir-22, mir-501, mir-365b, mir-660, mir-146a, let-7b and mir-31 was constructed. This signature significantly differentiated the high-risk group from the low-risk in terms of overall survival (OS)/ distant-relapse free survival (DRFS) (p value < 0.001). The prognostic value of the signature was further enhanced by incorporating other independent prognostic factors in a nomogram-based prediction model, yielding the highest AUC of 0.79 (95% CI: 0.72–0.86) at 5-year OS. Enrichment analyses confirmed that the differentially expressed genes were mainly involved in immune-related pathways such as adaptive immune response, humoral immune response and Th1 and Th2 cell differentiation. This eleven-TRM signature has great potential as a prognostic factor for breast cancer patients besides unravelling the dysregulated immune pathways in high-risk breast cancer.

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Section: Discussionmentioning

confidence: 83%

An Eleven-microRNA Signature Related to Tumor-Associated Macrophages Predicts Prognosis of Breast Cancer

Jayasingam

Citartan

Zin

et al. 2022

IJMS

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“…As shown in Figure 2(c) , a total of 17 cancer types had significantly downregulated PTPRT levels in cancer tissues compared to normal tissue in most cancer types (the expression of PTPRT in 12/17 cancer types was downregulated, Figure 2(c) ). In addition, some studies reported that the downregulation of PTPRT expression is associated with poor prognosis [ 22 , 23 ].…”

Section: Resultsmentioning

confidence: 99%

Association of PTPRT Mutations with Cancer Metastasis in Multiple Cancer Types

Chen

Liu

et al. 2022

BioMed Research International

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Metastasis is one of the characteristics of advanced cancer and the primary cause of cancer-related deaths from cancer, but the mechanism underlying metastasis is unclear, and there is a lack of metastasis markers. PTPRT is a protein-coding gene involved in both signal transduction and cellular adhesion. It is also known as a tumor suppressor gene that inhibits cell malignant proliferation by inhibiting the STAT3 pathway. Recent studies have reported that PTPRT is involved in the early metastatic seeding of colorectal cancer; however, the correlation between PTPRT and metastasis in other types of cancer has not been revealed. A combined analysis using a dataset from the genomics evidence neoplasia information exchange (GENIE) and cBioPortal revealed that PTPRT mutation is associated with poor prognosis in pan-cancer and non-small-cell lung cancer. The mutations of PTPRT or “gene modules” containing PTPRT are significantly enriched in patients with metastatic cancer in multiple cancers, suggesting that the PTPRT mutations serve as potential biomarkers of cancer metastasis.

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Section: Discussionmentioning

confidence: 99%

“…PTPR, a subfamily of class I PTPs, are involved in protein dephosphorylation, which has been shown to inhibit multiple cellular signaling pathways. Previous studies have demonstrated that PTPRD exerts a suppressive effect in breast cancer and liver cancer (27,28). Hsu et al demonstrated that deleterious PTPRT/ PTPRD alterations are associated with the shorter progressionfree survival of CRC patients who had received bevacizumab (29).…”

Section: Discussionmentioning

confidence: 99%

PTPRD/PTPRT mutation as a predictive biomarker of immune checkpoint inhibitors across multiple cancer types

Shang

Zhang

et al. 2022

Front. Immunol.

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BackgroundImmune checkpoint inhibitors (ICIs) are dramatically changing the treatment landscape of a variety of cancers. Nevertheless, the variability in ICI responses highlight the importance in identifying predictive biomarkers. PTPRD and PTPRT (PTPRD/PTPRT) are the phosphatases of JAK-STAT signaling, a critical pathway in anti-cancer immunity regulation. However, the pan-cancer association between PTPRD/PTPRT mutation and the efficacy of ICIs remains unclear across pan-cancer patients.MethodsWe analyzed the association between PTPRD/PTPRT mutations and patient outcomes using clinical data and genomic mutations from TCGA pan-cancer cohort. Furthermore, the ICI-treatment cohort was used to evaluate the relationship between PTPRD/PTPRT mutation and the efficacy of ICIs. Another ICIs-treatment cohort was used to validate the findings. The TCGA pan-cancer dataset was analyzed to explore the correlation between PTPRD/PTPRT mutations and immune signatures. Moreover, we combined four factors to construct a nomogram model that could be used to predict the survival of pan-cancer patients receiving ICI treatment. The calibration curves and area under the curve were applied to assess the performance of the model.ResultsPTPRD/PTPRT mutations were shown to be associated with a worse prognosis in TCGA cohort (P < 0.05). In the Samstein cohort, prolonged overall survival (OS) was observed in PTPRD/PTPRT mutant cancers, compared with wild-type cancers (mOS: 40.00 vs 16.00 months, HR = 0.570, 95%CI: 0.479-0.679, P < 0.0001). In the validation cohort, significant OS advantage was observed in PTPRD/PTPRT mutant patients (mOS: 31.32 vs 15.53 months, HR = 0.658, 95%CI: 0.464-0.934, P = 0.0292). Furthermore, PTPRD/PTPRT mutations were associated with a higher tumor mutational burden, MSI score, and TCR score (P < 0.0001). Enhanced immune signatures were found in the PTPRD/PTPRT mutant cancers (P < 0.05). Finally, we successfully established a nomogram model that could be used to predict the survival of NSCLC patients who received ICI treatment. Based on the risk score of the model, patients in the low-risk group showed a better mOS than those in the high-risk group (mOS: 2.75 vs 1.08 years, HR = 0.567, 95%CI: 0.492-0.654; P < 0.001).ConclusionsPTPRD/PTPRT mutations may be a potential biomarker for predicting ICI treatment responsiveness in multiple cancer types.

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PTPRT Could Be a Treatment Predictive and Prognostic Biomarker for Breast Cancer

Cited by 8 publications

References 31 publications

An Eleven-microRNA Signature Related to Tumor-Associated Macrophages Predicts Prognosis of Breast Cancer

An Eleven-microRNA Signature Related to Tumor-Associated Macrophages Predicts Prognosis of Breast Cancer

Association of PTPRT Mutations with Cancer Metastasis in Multiple Cancer Types

PTPRD/PTPRT mutation as a predictive biomarker of immune checkpoint inhibitors across multiple cancer types

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