T‑cell immunoglobulin and mucin domain‑containing protein‑3 and galectin‑9 protein expression: Potential prognostic significance in esophageal squamous cell carcinoma for Chinese patients

Hou, Nan; Ma, Jun; Li, Wei; Zhao, Lingdi; Gao, Quanli; Mai, Linh

doi:10.3892/ol.2017.7188

Cited by 14 publications

(14 citation statements)

References 40 publications

(48 reference statements)

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“…When stratified by tumor type, TIM-3 expression was not associated with OS in esophageal carcinoma, sarcoma, and renal cell carcinoma, but was correlated with favorable OS in triple-negative breast cancer; TIM-3 was related to worse OS in non-small cell lung cancer and gastric cancer. Evidence from some previous publications is consistent with the present results, such as esophageal carcinoma (no association) ( 29 , 41 ), sarcoma (no association) ( 23 ), renal cell carcinoma (no association) ( 24 ), non-small cell lung cancer (worse OS) ( 39 , 55 ), gastric cancer (worse OS) ( 28 , 38 ), and breast cancer (better CSS) ( 37 ). We found the correlation between TIM-3 expression and worse prognosis among most cancers, such as lung, gastric, cervical, ovarian, colorectal, bladder, pancreatic, hepatocellular, and oral squamous cell carcinomas, as well as diffuse large B-cell lymphoma.…”

Section: Discussionsupporting

confidence: 92%

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

Zang¹,

Hui²,

Wang³

et al. 2021

Front. Oncol.

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BackgroundAs 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.MethodsPublications 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.Results28 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.ConclusionsTIM-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.

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Section: Discussionsupporting

confidence: 92%

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

Zang¹,

Hui²,

Wang³

et al. 2021

Front. Oncol.

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“…Our results showed that in the analysis of the LCRT subgroup, ICs Additionally, PD-1 and ICs TIM-3 were both independent prognostic factors for DFS in our study; and high expression of ICs LAG-3, CD8, and CD3 was related to better DFS in univariate analysis. In line with our observation, it has been reported that the expression of ICBs can serve as a predictor for outcome [21,[23][24][25]. However, the correlation between PD-1, TIM-3 expression, remained controversial in various cancers [23,26,27].…”

Section: Discussionsupporting

confidence: 87%

Assessment of the expression and response of PD-1, LAG-3, and TIM-3 after neoadjuvant radiotherapy in rectal cancer

Peng

Xin

et al. 2021

neo

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Many studies have verified the safety of combined radiotherapy and immune checkpoint blockades iation dose or sequencing of combination. We aimed to evaluate the expression and response of PD-1, TIM-3, LAG-3 after neoadjuvant radiotherapy (NRT) and explore the possibility and optimal schedule of combining immunotherapy with radiotherapy in treating rectal cancer. Immunohistochemistry was performed to detect the expression of PD-1, TIM-3, LAG-3, CD8, and CD3. These molecules' expression was detected on the specimens of 76 rectal cancer patients following NRT and 13 of these patients before NRT. The expression of ICBs was assessed by the percentage of positive cells. The levels of PD-1 and immune cells (ICs) LAG-3 in rectal cancer increased after NRT (0% vs. 3%, P = 0.043 and 5% vs. 45%, P = 0.039, respectively). However, TIM-3 in ICs and tumor cells (TCs) were both decreased (80% vs. 50%, P = 0.011, 90% vs. 0%, P = 0.000, respectively). The LAG-3 expression was higher in patients treated with short-course RT than longcourse RT (22.5% vs. 8.0%, P = 0.0440 in ICs; 0% vs. 70%, P < 0.001 in TCs). On the co ntrary, CD8 was higher after long-course RT (15% vs. 8%, P = 0.0146). Interestingly, the level of ICs TIM-3 was low in > eight weeks after long-course RT (P = 0.045). The expressions of PD-1, ICs TIM-3, ICs LAG-3, CD3, and CD8 were associated with the disease-free survival (DFS) in univariate analysis (P = 0.036, 0.008, 0.018, 0.025, and 0.004, respectively). Adjusted by the relevant variables, PD-1 (HR 0.274; 95%

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“…Similar to PD-1, TIM-3 was mainly expressed in cellular membranes, but it was also expressed in the nucleus in prostate cancer and colorectal cancer [28, 30]. In bladder cancer and esophageal cancer, TIM-3 was both expressed in cellular membranes and cytoplasm [24, 32]. 5) TIM-3 also appears as a co-stimulatory signal in other non-tumor disease states [18–20].…”

Section: Discussionmentioning

confidence: 99%

Differential expression of TIM-3 between primary and metastatic sites in renal cell carcinoma

et al. 2019

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BackgroundDue to the significant heterogeneity of renal cell carcinoma (RCC), immune checkpoints may express differently between primary and metastatic tumor. We aimed to evaluate the differential expression of TIM-3 between the primary and metastatic sites of RCC.MethodsCases of RCC with metastases resected or biopsied at West China Hospital between January 2009 and November 2016 were included. Clinicopathological parameters were retrospectively extracted. SPPS 22.0, GraphPad Prism 6 and R statistical software were applied for data analysis.ResultsA total of 163 cases were included. Immunohistochemical results showed that the overall detection rate of TIM-3 was 56.4% (92/163). The detection rate of TIM-3 in the primary (53.0%, 44/83) was numerically higher than that of the metastasis (42.6%,79/174). Although the concordance rate of TIM-3 between the primary and metastasis was as high as 66.3% (55/83) in the paired cohort, a significant statistically difference of TIM-3 expression between the primary and metastasis was observed (χ2 = 4.664, p = 0.002), with a poor consistency (Kappa = 0.331, p = 0.002). Subsequent survival analysis suggested that TIM-3 expression either in the primary or metastatic tumor was associated with longer progression-free survival (PFS) (HR: 0.67, 95% CI 0.45–0.99, P = 0.02) and overall survival (OS) (HR: 0.52, 95% CI 0.33–0.82, P < 0.001). The expressions of TIM-3 in the primary, metastatic tumors and patients treated with targeted agents all played as favorable factors for PFS and OS. Further multivariate analysis showed that, in the whole cohort, TIM-3 expression in metastatic tumor increased the predicted accuracy (PA) of the whole model of PFS from 74.7 to 75.6% (P = 0.02). For OS, the PA of whole model was increased from 78.1 to 81.1% by adding TIM-3 expression in the metastasis (P = 0.005). The same trends were also observed in paired patients and patients treated with targeted agents. In conclusion, the expression difference between the primary and metastatic tumor of TIM-3 was significant. Biopsy or resection of the metastases may provide a more accurate biological information for clinician’s decision-making and the patient’s prognosis. What’s more, the role of TIM-3 in the RCC still remains controversy, further study are needed to verify the conclusion.

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T‑cell immunoglobulin and mucin domain‑containing protein‑3 and galectin‑9 protein expression: Potential prognostic significance in esophageal squamous cell carcinoma for Chinese patients

Cited by 14 publications

References 40 publications

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

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

Assessment of the expression and response of PD-1, LAG-3, and TIM-3 after neoadjuvant radiotherapy in rectal cancer

Differential expression of TIM-3 between primary and metastatic sites in renal cell carcinoma

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