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

ABSTRACT: The role of PTPRT in breast cancer was not comprehensively explored and well analyzed. Our study comprehensively searched available databases to analyze the clinical role of PTPRT in breast cancer. We found PTPRT was an antioncogene and could be used to distinguish different stages, age groups, molecular types, and grades for breast cancer. PTPRT might be primary resistance biomarkers for taxane, anthracycline, and ixabepilone but not be acquired resistance biomarkers. Higher PTPRT expression levels were associated with longer overall survival and recurrence-free survival. PTPRT was negatively associated with Ki67 and CDK4/6 but positively associated with BCL-2. PTPRT might be associated with cell cycle and microtubule, and tumor infiltration in B cell and macrophage cell. PTPRT could predict chemotherapy effectiveness and prognosis for breast cancer patients. PTPRT might inhibit tumor growth via disrupting the microtubule dynamics and cell cycle in breast cancer.

SUBMITTER: Li L

PROVIDER: S-EPMC8370817 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Li Lun L Xu Feng F Xie Pingfang P Yuan Liqin L Zhou Meirong M

BioMed research international 20210810

The role of PTPRT in breast cancer was not comprehensively explored and well analyzed. Our study comprehensively searched available databases to analyze the clinical role of PTPRT in breast cancer. We found PTPRT was an antioncogene and could be used to distinguish different stages, age groups, molecular types, and grades for breast cancer. PTPRT might be primary resistance biomarkers for taxane, anthracycline, and ixabepilone but not be acquired resistance biomarkers. Higher PTPRT expression le ...[more]

PMID: 34414233

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Project description: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.

Project description:BackgroundRecQ-mediated genome instability 2 (RMI2) maintains genome stability by promoting DNA damage repair. It has been reported to accelerate the progression of several tumors. However, the functional mechanism of RMI2 in breast cancer remains unclear.MethodsGene expression profiles were obtained from TCGA, GTEx, and GEO databases. The expression of RMI2 and its prognostic value in breast cancer was explored. In addition, we calculated pooled standardized mean deviation (SMD) and performed a summary receiver operating characteristic (sROC) curve analysis to further determine RMI2 expression status and diagnostic significance. The functions and related signaling pathways were investigated based on GO and KEGG analyses. The PPI network was constructed by combining the STRING database and Cytoscape software. Subsequently, in vitro assays were conducted to detect the effect of RMI2 on the proliferation and migration of breast cancer cells.ResultsThe expression of RMI2 was markedly upregulated in breast cancer tissues relative to that in normal tissues. Moreover, pooled SMD further confirmed the overexpression of RMI2 in breast cancer (SMD = 1.29, 95% confidence interval (CI): 1.18-1.41, p = 0.000). The sROC curve analysis result suggested that RMI2 had a relatively high diagnostic ability in breast cancer (AUC = 0.87, 95% CI: 0.84-0.90). High RMI2 expression was associated with poor prognosis. GO and KEGG analyses revealed that RMI2 was closely related to cell adhesion, various enzyme activities, and PI3K/AKT signaling pathway. PPI analysis showed that RMI2 had interactions with proteins involved in DNA damage repair. knockdown of RMI2 remarkably inhibited the proliferation and migration of breast cancer cells, while overexpression of RMI2 exerted the opposite effects. Furthermore, we identified that RMI2 accelerates the proliferation and migration of breast cancer cells via activation of the PI3K/AKT pathway.ConclusionThe results suggest that RMI2 is a potential diagnostic and prognostic biomarker associated with cell proliferation and migration, and may be used as a novel therapeutic target for breast cancer in the future.

Project description:Background: Triple-negative breast cancer (TNBC) is characterized by a more aggressive biological behavior and unfavorable outcome. Circulating and histological expression of THBS2 has been demonstrated to be a novel diagnostic and prognostic biomarker in patients with various types of tumors. However, few studies have evaluated the predictive and prognostic value of THBS2 in TNBC specifically. Methods: In total, 185 triple-negative breast cancer patients (TNBC) with preoperative neoadjuvant chemotherapy were enrolled in this study. Serum THBS2 (sTHBS2) level was measured both prior to the start of NAC and at surgery by enzyme-linked immunosorbent assay (ELISA). Histological THBS2 (hTHBS2) expression in patients with residual tumors was evaluated by immunohistochemistry (IHC) staining method. Correlations between variables and treatment response were studied. Kaplan-Meier plots and Cox proportional hazard regression model were applied for survival analysis. Functional activities of THBS2 in TNBC cells were determined by CCK-8 assay, colony formation, wound healing, and transwell assay. Results: Of the 185 patients, 48 (25.9%) achieved pathological complete response (pCR) after completion of NAC. Elevated pCR rates were observed in patients with a lower level of sTHBS2 at surgery and higher level of sTHBS2 change (OR = 0.88, 95%CI: 0.79-0.98, p = 0.020 and OR = 1.12, 95%CI: 1.02-1.23, p = 0.015, respectively). In survival analysis, hTHBS2 expression in residual tumor was of independent prognostic value for both disease-free survival (HR = 2.21, 95%CI = 1.24-3.94, p = 0.007) and overall survival (HR = 2.07, 95%CI = 1.09-3.92, p = 0.026). For functional studies, THBS2 was indicated to inhibit proliferation, migration, and invasion abilities of TNBC cells in vitro. Conclusion: Our findings confirmed the value of serum THBS2 level to predict pCR for TNBC patients and the prognostic performance of histological THBS2 expression in non-pCR responders after NAC. THBS2 might serve as a promising functional biomarker for patients with triple-negative breast cancer.

Project description:GADD45B acts as a member of the growth arrest DNA damage-inducible gene family, which has demonstrated to play critical roles in DNA damage repair, cell growth, and apoptosis. This study aimed to explore the potential relationship between GADD45B expression and tumor progression and evaluate the clinical value of GADD45B in stage II colorectal cancer (CRC). The expression patterns and prognostic value of GADD45B in CRC were analyzed based on The Cancer Genomic Atlas (TCGA). GADD45B expression features of 306 patients with stage II CRC and 201 patients with liver metastasis of CRC were investigated using immunochemical staining on tissue microarrays. Afterward, survival analysis and stratification analysis were performed in stage II to explore the prognostic and predictive significance of GADD45B. Overexpressed GADD45B is associated with poorer prognosis for CRC patients both in overall survival (OS) (p < 0.001) and disease-free survival (DFS) (p = 0.001) based on the TCGA database. Analysis results according to the stage II CRC cohort and the liver metastatic CRC cohort revealed that GADD45B was gradually upregulated in normal mucosa including primary colorectal cancer (PCC). Colorectal liver metastases (CLM) tissues were arranged in order (normal tissue vs. PCC p = 0.005 and PCC vs. CLM p = 0.001). The low GADD45B group had a significantly longer five-year OS (p = 0.001) and progression-free survival (PFS) (p < 0.001) than the high GADD45B group for the stage II patients. The multivariate Cox regression analysis results proved that the expression level of GADD45B was an independent prognostic factor for stage II after radical surgery (OS: Hazard Ratio (HR) 0.479, [95% confidence interval (CI) 0.305⁻0.753] and PFS:HR 0.490, [95% CI 0.336⁻0.714]). In high GADD45B expression subgroup of stage II cohort, the patients who underwent adjuvant chemotherapy had longer PFS than those who did not (p = 0.008). High expression levels of GADD45B is an independent prognostic factor of decreased OS and PFS in stage II CRC patients. The stage II CRC patients with high GADD45B expression might benefit from adjuvant chemotherapy.

Dataset Information

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

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

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