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Immune-related key gene CLDN10 correlates with lymph node metastasis but predicts favorable prognosis in papillary thyroid carcinoma.

ABSTRACT: The functions of immune cells in lymph node metastasis (LNM) have attracted considerable attention. This study aimed to screen the key immune-related and LNM-related genes in PTC. In the discovery phase, the immune-related genes in LNM were screened by using bioinformatics methods. In the validation phases, the association of the genes with LNM was first confirmed in a cohort from The Cancer Genome Atlas and a cohort based on a tissue chip. Then, the relationship of the genes with immune cell infiltration was further explored. Consequently, CLDN10 was identified, and its high expression was correlated with the presence of LNM in PTC but predicted a favorable prognosis. High CLDN10 expression was positively correlated with the infiltration of several immune cells, such as B cells, CD8+T cells, and macrophages. High CLDN10 expression may improve the outcomes of patients with PTC by increasing immune cell infiltration, although it might be associated with LNM. In conclusion, although CLDN1 might be correlated with LNM, it may also increase the infiltration of immune cells, including CD8+T cells and macrophages, and improve the clinical outcomes of patients with PTC. The effects of tumor purity and immune cell infiltration need to be considered in prognosis evaluation.

SUBMITTER: Xiang Z

PROVIDER: S-EPMC7041783 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Immune-related key gene CLDN10 correlates with lymph node metastasis but predicts favorable prognosis in papillary thyroid carcinoma.

Xiang Zhaolan Z Zhong Cheng C Chang Aoshuang A Ling Junjun J Zhao Houyu H Zhou Wei W Zhuo Xianlu X

Aging 20200211 3

The functions of immune cells in lymph node metastasis (LNM) have attracted considerable attention. This study aimed to screen the key immune-related and LNM-related genes in PTC. In the discovery phase, the immune-related genes in LNM were screened by using bioinformatics methods. In the validation phases, the association of the genes with LNM was first confirmed in a cohort from The Cancer Genome Atlas and a cohort based on a tissue chip. Then, the relationship of the genes with immune cell in ...[more]

PMID: 32045884

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Project description:BackgroundDistant metastasis (DM) is a rare event and has a negative effect on the prognosis for papillary thyroid carcinoma (PTC). The relationship between cervical lymph node metastasis and DM is complicated and unclear. This study aimed to evaluate the impact of N stage subclassification on different distant metastasis sites based on age stratification, especially for patients with papillary thyroid microcarcinoma.MethodsA total of 28,712 patient with PTC cases between 2010 and 2018 were extracted from the Surveillance, Epidemiology, and End Results database. Multivariable logistic regression analysis was utilized to adjust for confounding variables. Risk stratification, including positive lymph node number and lymph node ratio, was established by receiver operating characteristic curves to help predict DM.ResultsLung was the most common metastatic site regardless of N0, N1a disease, or N1b disease. As the N stage increased, the higher the rate of DM identified. After age stratification, only N1b disease significantly increased the risk of lung metastasis (LM; odds ratio, OR = 20.45, P < 0.001) rather than bone metastasis (BM; OR = 3.46, P > 0.05) in younger patients. However, in older patients, N1b disease significantly increased the risk of both LM (OR = 4.10, P < 0.001) and BM (OR = 2.65, P = 0.007). In patients with papillary thyroid microcarcinoma (PTMC), N1a disease did not increase the risk of DM, LM, and BM compared with N0 disease (P > 0.05). Furthermore, combined N stage with risk stratification has well performance in predicting DM (area under the curve, AUC = 0.761). Similar results were shown in PTC patients with LM (AUC = 0.770) and BM (AUC = 0.729).ConclusionOverall, the incidence of DM significantly increased with the progress of N disease after age stratification. N1a disease did not increase the risk of DM in PTMC patients, regardless of LM or BM. Combined N stage with risk stratification may be beneficial for DM prediction.

Project description:BackgroundPapillary thyroid microcarcinoma (PTMC) is characterized by its favorable prognosis and potential for active surveillance (AS) as a management option. However, the presence of cervical lymph node (LN) metastasis, especially lateral LN metastasis, significantly impacts management and prognosis. Previous studies have focused on post-surgery risk factors for cervical LN metastasis. This study aims to identify predictors of lateral LN metastasis by analyzing pre-operative ultrasonographic findings alongside clinicopathological factors.MethodsA retrospective review of medical records was conducted for patients with PTMC who underwent surgery at Chonnam National University Hwasun Hospital between 2004 and 2013. This is a case-control study that compares patients with lateral LN metastasis (N1b) to age- and sex-matched patients without LN metastasis (N0). Subgroup analysis was performed to evaluate risk factors of skip metastasis.ResultsThe study included 90 patients with PTMC with lateral LN metastasis (N1b) and 268 age- and sex-matched patients without LN metastasis (N0). The mean age was 49.3 years, and female patients were dominant in both groups. Structural recurrences of 4.4% (4/90) were observed only in the N1b group. The N1b group exhibited a higher frequency of upper lobe tumor location compared to the N0 group (38.9% vs. 16.0%, p < 0.001). There was no significant difference in the locations with the presence of invasion to adjacent organs. A higher proportion of non-parallel shape was observed in the N1b group than the N0 group (80.0% vs. 66.0%, p = 0.013). There were no differences in echogenicity, sonographic feature, margin, and AP diameter of the thyroid gland between the two groups. In multivariate analysis, independent risk factors for lateral LN metastasis included extrathyroidal extension, multiplicity, upper lobe tumor location, and non-parallel shape. Skip metastasis in patients with PTMC was associated with upper lobe tumor location.ConclusionDetailed ultrasound examinations, evaluating tumor location, number, orientation, and the presence of ETE, are crucial in accurately predicting lateral LN metastasis especially when primary tumor was in the upper lobe to avoid missing skip metastasis. These evaluations can help guide the decision between AS and immediate surgery in patients with PTMC.

Dataset Information

Immune-related key gene CLDN10 correlates with lymph node metastasis but predicts favorable prognosis in papillary thyroid carcinoma.

Publications

Immune-related key gene CLDN10 correlates with lymph node metastasis but predicts favorable prognosis in papillary thyroid carcinoma.

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