Dataset Information

TIM-3 as a Prognostic Marker and a Potential Immunotherapy Target in Human Malignant Tumors: A Meta-Analysis and Bioinformatics Validation.

ABSTRACT:

Background

As a novel immune checkpoint molecular, T-cell immunoglobulin mucin 3 (TIM-3) is emerging as a therapeutic target for cancer immunotherapy. However, the predictive role of TIM-3 in cancer remains largely undetermined. This study was designed to investigate the role of TIM-3 in cancer.

Methods

Publications were searched using multiple databases. The hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. To further confirm the prognostic effect of TIM-3, The Cancer Genome Atlas (TCGA) data were applied. Functional analysis of TIM-3 was also investigated.

Results

28 studies with 7284 patients with malignant tumors were identified. Based on multivariate Cox regression analysis, TIM-3 was an independent prognostic indicator for poor overall survival (OS) (HR= 1.54, 95% CI = 1.19-1.98, P = 0.001). However, TIM-3 was not correlated with cancer-specific survival and disease-free survival (DFS). Particularly, TIM-3 showed a worse prognosis in non-small cell lung carcinoma and gastric cancer; but it showed a favorable prognosis in breast cancer. Functional analysis showed that TIM-3 was closely correlated with immune responses such as T-cell activation and natural killer cell-mediated cytotoxicity. Moreover, TIM-3 expression was found to be related to worse OS in 9491 TCGA patients (HR = 1.2, P < 0.001), but was not associated with DFS.

Conclusions

TIM-3 was an independent prognostic factor. Meanwhile, TIM-3 played a crucial role in tumor immune responses. This supports TIM-3 as a promising target for cancer immunotherapy.

SUBMITTER: Zang K

PROVIDER: S-EPMC7938756 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

TIM-3 as a Prognostic Marker and a Potential Immunotherapy Target in Human Malignant Tumors: A Meta-Analysis and Bioinformatics Validation.

Zang Kui K Hui Liangliang L Wang Min M Huang Ying Y Zhu Xingxing X Yao Bin B

Frontiers in oncology 20210222

<h4>Background</h4>As a novel immune checkpoint molecular, T-cell immunoglobulin mucin 3 (TIM-3) is emerging as a therapeutic target for cancer immunotherapy. However, the predictive role of TIM-3 in cancer remains largely undetermined. This study was designed to investigate the role of TIM-3 in cancer.<h4>Methods</h4>Publications were searched using multiple databases. The hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. To further confirm the prognostic effect of TIM-3, ...[more]

PMID: 33692946

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Project description:BackgroundTryptophan 2,3-dioxygenase (TDO2) is one of the emerging immune checkpoints. Meanwhile, TDO2 is also a key enzyme in the tryptophan (Trp)-kynurenine (Kyn) signaling pathway. Many studies have evaluated that TDO2 is highly expressed in various malignant tumor patients and plays a prognostic role. However, the sample size of a single prognostic study was small, and the results were still controversial.MethodsWe used Stata software and referenced the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement to conduct a meta-analysis on TDO2 and its clinical features and prognosis. We searched the PubMed, Cochrane Library, and Web of Science databases to find publications concerning TDO2 expression in malignant tumor patients up to June 2021. We used the Newcastle-Ottawa Scale (NOS) to evaluate the bias risk of the included literature. Risk ratios (RRs) and hazard ratios (HRs) were used for clinical outcomes, specifically overall survival (OS) and progression-free survival (PFS). In addition, we used data from The Cancer Genome Atlas (TCGA) to verify our conclusions.ResultsNine studies including 667 patients with malignant tumors were identified. Our results suggested that overexpression of TDO2 was statistically correlated with poor OS and poor PFS (HR = 2.58, 95% CI = 1.52-4.40, p = 0.0005; HR = 2.38, 95% CI = 0.99-5.73, p = 0.05). In terms of clinicopathological characteristics, the overexpression level of TDO2 was statistically correlated with TNM (tumor-node-metastasis) stage (RR = 0.65, 95% CI = 0.48-0.89, p = 0.002) and regional lymph node metastasis (RR = 0.76, 95% CI = 0.59-0.99, p = 0.04). Subgroup analysis revealed the potential sources of heterogeneity. In addition, bioinformatics studies suggested that the level of TDO2 was high in malignant tumors and higher in cancer tissue than in matched paracarcinoma tissue. Gene enrichment analysis showed that TDO2 was closely related to immune response.ConclusionOverall, TDO2 may be a biomarker for the survival and prognosis of patients with malignant tumors and a potential therapeutic target in the future.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=260442, identifier (CRD42021260442).

Project description:BackgroundDespite the diverse genetic mutations in head and neck cancer, the chemotherapy outcome for this cancer has not improved for decades. It is urgent to select prognostic factors and therapeutic targets for oropharyngeal cancer to establish precision medicine. Recent studies have identified PSMD1 as a potential prognostic marker in several cancers. We aimed to assess the prognostic significance of PSMD1 expression in oropharyngeal squamous cell carcinoma (OPSCC) patients using immunohistochemistry.MethodsWe studied 64 individuals with OPSCC tissue from surgery at Seoul National University Bundang Hospital between April 2008 and August 2017. Immunostaining analysis was conducted on the tissue microarray (TMA) sections (4 μm) for p16 and PSMD1. H-score, which scale from 0 to 300, was calculated from each nucleus, cytoplasm, and cellular expression. Clinicopathological data were compared with Chi-squared test, Fisher's exact test, t-test, and logistic regression. Survival data until 2021 were achieved from national statistical office of Korea. Kaplan-Meier method and cox-regression model were used for disease-specific survival (DSS) analysis.ResultsH-score of 90 in nucleus was appropriate cutoff value for 'High PSMD1 expression' in OPSCC. Tonsil was more frequent location in low PSMD1 group (42/52, 80.8%) than in high PSMD1 group (4/12, 33.3%; P = .002). Early-stage tumor was more frequent in in low PSMD1 group (45/52, 86.5%) than in high PSMD1 group (6/12, 50%; P = .005). HPV was more positive in low PSMD1 group (43/52, 82.7%) than in high PSMD1 group (5/12, 41.7%; P = .016). Patients with PSMD1 high expression showed poorer DSS than in patients with PSMD1 low expression (P = .006 in log rank test). In multivariate analysis, PSMD1 expression, pathologic T staging, and specimen age were found to be associated with DSS (P = .011, P = .025, P = .029, respectively).ConclusionsIn our study, we established PSMD1 as a negative prognostic factor in oropharyngeal squamous cell carcinoma, indicating its potential as a target for targeted therapy and paving the way for future in vitro studies on drug repositioning.

Dataset Information

TIM-3 as a Prognostic Marker and a Potential Immunotherapy Target in Human Malignant Tumors: A Meta-Analysis and Bioinformatics Validation.

Background

Methods

Results

Conclusions

Publications

TIM-3 as a Prognostic Marker and a Potential Immunotherapy Target in Human Malignant Tumors: A Meta-Analysis and Bioinformatics Validation.

Similar Datasets

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