Upregulation of TTK expression is associated with poor prognosis and immune infiltration in endometrial cancer patients

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Abstract

Background

Threonine and tyrosine kinase (TTK) is associated with invasion and metastasis in various tumors. However, the prognostic importance of TTK and its correlation with immune infiltration in endometrial cancer (EC) remain unclear.

Methods

The expression profile of TTK was analyzed using data from The Cancer Genome Atlas (TCGA) and the Clinical Proteome Cancer Analysis Consortium (CPTAC). TTK protein and mRNA levels were verified in EC cell lines. Receiver operating characteristic (ROC) curve analysis was used to evaluate the ability of TTK to distinguish between normal and EC tissues. K-M survival analysis was also conducted to evaluate the impact of TTK on survival outcomes. Protein‒protein interaction (PPI) networks associated with TTK were explored using the STRING database. Functional enrichment analysis was performed to elucidate the biological functions of TTK. TTK mRNA expression and immune infiltration correlations were examined using the Tumor Immune Estimation Resource (TIMER) and the Tumor-Immune System Interaction Database (TISIDB).

Results

TTK expression was significantly greater in EC tissues than in adjacent normal tissues. Higher TTK mRNA expression was associated with tumor metastasis and advanced TNM stage. The protein and mRNA expression of TTK was significantly greater in tumor cell lines than in normal endometrial cell lines. ROC curve analysis revealed high accuracy (94.862%), sensitivity (95.652%), and specificity (94.894%) of TTK in differentiating EC from normal tissues. K-M survival analysis demonstrated that patients with high TTK expression had worse overall survival (OS) and disease-free survival (DFS) rates. Correlation analysis revealed that TTK mRNA expression was correlated with B cells and neutrophils.

Conclusion

TTK upregulation is significantly associated with poor survival outcomes and immune infiltration in patients with EC. TTK can serve as a potential biomarker for poor prognosis and a promising immunotherapy target in EC. Further investigation of the role of TTK in EC may provide valuable insights for therapeutic interventions and personalized treatment strategies.

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Most cited references 38

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Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma

Roger Stupp, Warren P Mason, Martin J van den Bent … (2005)

Glioblastoma, the most common primary brain tumor in adults, is usually rapidly fatal. The current standard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible, followed by adjuvant radiotherapy. In this trial we compared radiotherapy alone with radiotherapy plus temozolomide, given concomitantly with and after radiotherapy, in terms of efficacy and safety. Patients with newly diagnosed, histologically confirmed glioblastoma were randomly assigned to receive radiotherapy alone (fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy) or radiotherapy plus continuous daily temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle). The primary end point was overall survival. A total of 573 patients from 85 centers underwent randomization. The median age was 56 years, and 84 percent of patients had undergone debulking surgery. At a median follow-up of 28 months, the median survival was 14.6 months with radiotherapy plus temozolomide and 12.1 months with radiotherapy alone. The unadjusted hazard ratio for death in the radiotherapy-plus-temozolomide group was 0.63 (95 percent confidence interval, 0.52 to 0.75; P<0.001 by the log-rank test). The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiotherapy alone. Concomitant treatment with radiotherapy plus temozolomide resulted in grade 3 or 4 hematologic toxic effects in 7 percent of patients. The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma resulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity. Copyright 2005 Massachusetts Medical Society.

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pROC: an open-source package for R and S+ to analyze and compare ROC curves

Xavier Robin, Natacha Turck, Alexandre Hainard … (2013)

Background Receiver operating characteristic (ROC) curves are useful tools to evaluate classifiers in biomedical and bioinformatics applications. However, conclusions are often reached through inconsistent use or insufficient statistical analysis. To support researchers in their ROC curves analysis we developed pROC, a package for R and S+ that contains a set of tools displaying, analyzing, smoothing and comparing ROC curves in a user-friendly, object-oriented and flexible interface. Results With data previously imported into the R or S+ environment, the pROC package builds ROC curves and includes functions for computing confidence intervals, statistical tests for comparing total or partial area under the curve or the operating points of different classifiers, and methods for smoothing ROC curves. Intermediary and final results are visualised in user-friendly interfaces. A case study based on published clinical and biomarker data shows how to perform a typical ROC analysis with pROC. Conclusions pROC is a package for R and S+ specifically dedicated to ROC analysis. It proposes multiple statistical tests to compare ROC curves, and in particular partial areas under the curve, allowing proper ROC interpretation. pROC is available in two versions: in the R programming language or with a graphical user interface in the S+ statistical software. It is accessible at http://expasy.org/tools/pROC/ under the GNU General Public License. It is also distributed through the CRAN and CSAN public repositories, facilitating its installation.

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TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells.

Taiwen Li, Jingyu Fan, Binbin Wang … (2017)

Recent clinical successes of cancer immunotherapy necessitate the investigation of the interaction between malignant cells and the host immune system. However, elucidation of complex tumor-immune interactions presents major computational and experimental challenges. Here, we present Tumor Immune Estimation Resource (TIMER; cistrome.shinyapps.io/timer) to comprehensively investigate molecular characterization of tumor-immune interactions. Levels of six tumor-infiltrating immune subsets are precalculated for 10,897 tumors from 32 cancer types. TIMER provides 6 major analytic modules that allow users to interactively explore the associations between immune infiltrates and a wide spectrum of factors, including gene expression, clinical outcomes, somatic mutations, and somatic copy number alterations. TIMER provides a user-friendly web interface for dynamic analysis and visualization of these associations, which will be of broad utilities to cancer researchers. Cancer Res; 77(21); e108-10. ©2017 AACR.

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Author and article information

Contributors

Yilang Wang: oncowang@163.com

Xiaoqing Yang: ntyxq169@126.com

Journal

Journal ID (nlm-ta): Cancer Cell Int

Journal ID (iso-abbrev): Cancer Cell Int

Title: Cancer Cell International

Publisher: BioMed Central (London )

ISSN (Electronic): 1475-2867

Publication date (Electronic): 9 January 2024

Publication date PMC-release: 9 January 2024

Publication date Collection: 2024

Volume: 24

Electronic Location Identifier: 20

Affiliations

[1 ]GRID grid.440642.0, ISNI 0000 0004 0644 5481, Department of Obstetrics and Gynecology, , Affiliated Hospital of Nantong University, Medical School of Nantong University, ; Nantong, China

[2 ]GRID grid.260483.b, ISNI 0000 0000 9530 8833, Department of Cancer Research Center, Nantong Tumor Hospital, , The Affiliated Tumor Hospital of Nantong University, ; Nantong, China

[3 ]GRID grid.260483.b, ISNI 0000 0000 9530 8833, Department of Oncology, , The Affiliated Maternity and Child Health Care Hospital of Nantong University, ; Nantong, China

[4 ]Department of Gynaecology and Obstetrics, JiangSu XiangShui Hospital of Chinese Medicine, XiangShui, China

Article

Publisher ID: 3192

DOI: 10.1186/s12935-023-03192-2

PMC ID: 10775523

PubMed ID: 38195567

SO-VID: 295027e8-a47a-401f-a404-566068cf4d2e

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 16 September 2023

Date accepted : 25 December 2023

Funding

Funded by: Third-level Talents of the Seventh Phase of Jiangsu Province 333 Talent Plan

Award ID: No. 2022-3-29-061

Custom metadata

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: endometrial cancer,threonine and tyrosine kinase,ttk,prognosis,immune infiltrate

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: endometrial cancer, threonine and tyrosine kinase, ttk, prognosis, immune infiltrate

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Upregulation of TTK expression is associated with poor prognosis and immune infiltration in endometrial cancer patients

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Karger: Oncology

Most cited references 38

Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma

pROC: an open-source package for R and S+ to analyze and compare ROC curves

TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells.

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