Clinicopathological and prognostic value of SIRT6 in patients with solid tumors: a meta-analysis and TCGA data review

Abstract

Purposes: In addition to its role in cellular progression and cancer, SIRT6, a member of nicotinamide adenine dinucleotide (NAD⁺)-dependent class III deacylase sirtuin family, serves a variety of roles in the body's immune system. In this study, we sought to determine the relationship between the expression of SIRT6 and the clinicopathological outcomes of patients with solid tumours by conducting a meta-analysis of the available data.

Methods: The databases PubMed and ISI Web of Science were searched for relevant literature, and the results were presented here. Using Stata16.0, a meta-analysis was conducted to determine the impact of SIRT6 on clinicopathological characteristics and prognosis in malignancy patients. The results were published in the journal Cancer Research. The dataset from the Cancer Genome Atlas (TCGA) was used to investigate the prognostic significance of SIRT6 in various types of tumors.

Results: The inclusion and exclusion criteria were met by 15 studies. In patients with solid tumours, reduced SIRT6 expression was found to be related with improved overall survival (OS) (HR = 0.66, 95% CI = 0.45-0.97, P < 0.001) as well as improved disease-free survival (DFS) (HR = 0.48, 95% CI = 0.26-0.91, P < 0.001). Low SIRT6 expression was found to be associated with a better OS in breast cancer (HR = 0.49, 95% CI = 0.27-0.89, P = 0.179), but was found to be associated with a worse OS in gastrointestinal cancer (gastric cancer and colon cancer) (HR = 1.83, 95% CI = 1.20-2.79, P = 0.939) after subgroup analysis. In terms of clinicopathological characteristics, SIRT6 expression was found to be linked with distant metastasis (OR = 2.98, 95% CI = 1.59-5.57, P = 0.694). When the data from the TCGA dataset was compared to normal tissue, it was discovered that SIRT6 expression was significantly different in 11 different types of cancers. Meanwhile, reduced SIRT6 expression was shown to be associated with improved OS (P < 0.05), which was consistent with the findings of the meta-analysis. Aside from that, the expression of SIRT6 was found to be associated with both gender and clinical stage.

Conclusion: The overall data of the present meta-analysis indicated that low expression of SIRT6 may predict a favorable survival for patients with solid tumors.

Keywords: Meta-analysis; Prognosis; SIRT6; Solid tumors.

Fig. 1

Flow diagram of the selection of eligible studies

Fig. 2

A Forest plot of the association between SIRT6 expression and OS; B subgroup analysis by tumor type

Fig. 3

Forest plot describing the association between low-expressed SIRT6 and DFS

Fig. 4

Sensitivity analysis of each study. A Sensitivity analysis for OS; B Sensitivity analysis for DFS

Fig. 5

Funnel plot for publication bias. A Funnel plot for OS; B Funnel plot for DFS

Fig. 6

Funnel plot for publication bias regarding clinicopathological features. A Gender; B Tumor differentiation; C T status; D Lymph node metastasis; E Distant metastasis; F TNM stage

Fig. 7

Expression of SIRT6 was significantly different in 11 malignant tumor tissues (red) and paired normal tissues (gray). Bladder Urothelial Carcinoma (BLCA); Breast invasive carcinoma (BRCA); Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC); Cholangiocarcinoma (CHOL); Colon adenocarcinoma (COAD); Esophageal carcinoma (ESCA); glioblastoma multiforme (GBM); Head and Neck squamous cell carcinoma (HNSC); Kidney Chromophobe (KIRC); Thyroid carcinoma (THCA) and Uterine Corpus Endometrial Carcinoma (UCEC)

Fig. 8

Forest plot for prognosis of SIRT6 in tumors analyzed by univariate Cox regression in TCGA. Adrenocortical carcinoma (ACC), Kidney Chromophobe (KICH), Testicular Germ Cell Tumors (TGCT), Thymoma (THYM), Uterine Carcinosarcoma (UCS) and Uveal Melanoma (UVM)

Fig. 9

Kaplan–Meier survival curves of different tumor types of patients in TCGA dataset. A Overall survival plot of SIRT6 in all 17 types of tumors (n = 4678, logrank P < 0.05); B Disease-free survival plot of SIRT6 in all 17 types of tumors (n = 2828, logrank P = 0.164); C Overall survival plot of SIRT6 in gastrointestinal cancer (n = 609, logrank P < 0.05); D Disease-free survival plot of SIRT6 in gastrointestinal cancer (n = 260, logrank P < 0.05); E Overall survival plot of SIRT6 in breast cancer (n = 1082, logrank P = 0.826); F Disease-free survival plot of SIRT6 in breast cancer (n = 952, logrank P < 0.05); G Overall survival plot of SIRT6 in head and neck cancer (n = 1010, logrank P < 0.05); H Disease-free survival plot of SIRT6 in head and neck cancer (n = 482, logrank P = 0.583); I Overall survival plot of SIRT6 in urogenital cancer (n = 2130, logrank P < 0.05); J Disease-free survival plot of SIRT6 in urogenital cancer (n = 1109, logrank P < 0.05); K Overall survival plot of SIRT6 in other system cancer (n = 401, logrank P < 0.05); L Disease-free survival plot of SIRT6 in other system cancer (n = 25, logrank P = 0.149)

Fig. 10

Violin plot demonstrated that expression of SIRT6 was significantly associated with clinical stage (P < 0.001) and gender (P < 0.001). A Clinical stage; B Gender