Metallothioneins may be a potential prognostic biomarker for tumors

Abstract

Background:Metallothioneins (MTs) were reported to be associated with many kinds of tumors’ prognosis, although MTs expression varied greatly among tumors. To assess the prognostic value of Metallothioneins (MTs) in different kinds of tumors, comprehensive literature search was conducted to perform a meta-analysis.Methods:Eligible studies were identified by PubMed, MEDLINE, Web of Science (WOS), the Cochrane Library of Systematic Reviews, EMBASE, China National Knowledge Infrastructure (CNKI), WANFANG database and SinoMed database up to December 2017, which was designed to assess the prognostic value of MTs in different kinds of tumors. The main endpoint events were overall survival (OS) and disease-free survival (DFS). Hazard ratios (HRs) and its variance were retrieved from the original studies directly or calculated using Engauge Digitizer version 4.1. Random or fixed effects model meta-analysis was employed depending on the heterogeneity. Publication bias was evaluated by funnel plots, Begg and Egger tests.Results:A total of 22 studies were enrolled in this meta-analysis, including 2843 tumor tissues (1517 were MTs negative/low, and 1326 were MTs high). Results showed that there was significant association between MTs expression and tumors’ OS (HR = 1.60; 95%CI 1.34∼1.92, P < .00001). Subgroup analysis showed that high level of MTs expression was associated with prolonged OS in liver cancer (HR = 0.65, 95%CI 0.48∼0.89, P = .007), but it was on the contrary in the tumor of ovary (HR = 1.47, 95%CI 1.01∼2.14, P = .04), bladder (HR = 1.71, 95%CI 1.21∼2.42, P = .002), intestine (HR = 3.13, 95%CI 1.97∼4.97, P < .00001), kidney (HR = 3.31, 95%CI 1.61∼6.79, P = .001). However, there was no significant association between MTs expression and OS in breast (HR = 1.02, 95%CI 0.69∼1.51, P = .93).Conclusions:MTs could be taken as a potential prognostic biomarker for tumors, and uniqueness of MTs prognostic value in liver cancer deserved further study.

Resolving the immune landscape of human prostate at a single-cell level in health and cancer

“…Two of the three macrophage populations were transcriptionally similar (MAC1 and MAC2) (Figure 3B), while MAC-MT cells formed a completely distinct cluster (Figure 3A) and expressed high levels of the metallothionein family genes (Figure 3B), encoding cysteine-rich proteins that bind divalent heavy metal ions and are involved in the cellular transport, storage, and metabolism of metal ions (Miles et al, 2000). High expression of metallothioneins has been noted in prostate cancer (Wei et al, 2008, Wang et al, 2018, but the MAC-MT cluster contained cells from both our dataset and that generated from normal, young human prostate tissue (Henry et al, 2018;Figure S4C), confirming that these cells exist in healthy prostate tissue in homeostasis. We also validated the presence of MAC-MT in the three other published scRNaseq datasets of both normal prostate and prostate cancer (Figures 3C and S4D).…”

Metallothioneins and Megalin Expression Profiling in Premalignant and Malignant Oral Squamous Epithelial Lesions

“…Data on the paracrine MT-megalin axis are scarce and mostly limited to the central nervous system (CNS), where such interactions were found to be associated with neuronal survival, neuroprotection and neuroregeneration [ 24 , 26 , 28 , 29 , 30 ]. In the view of this knowledge, particular interest was drawn to the possible role of MTs in the processes of oncogenesis and tumor progression, and MTs expression was being extensively investigated on that trail [ 1 , 3 , 33 , 34 , 35 ]. However, despite the large corpus of data in this field, they are inconsistent and do not allow convincing conclusions on MTs impact on carcinogenesis, failing to firmly establish these molecules as a reliable diagnostic and prognostic marker of oncological diseases [ 33 , 34 ].…”

“…In the view of this knowledge, particular interest was drawn to the possible role of MTs in the processes of oncogenesis and tumor progression, and MTs expression was being extensively investigated on that trail [ 1 , 3 , 33 , 34 , 35 ]. However, despite the large corpus of data in this field, they are inconsistent and do not allow convincing conclusions on MTs impact on carcinogenesis, failing to firmly establish these molecules as a reliable diagnostic and prognostic marker of oncological diseases [ 33 , 34 ]. The heterogeneity of the data collected so far suggests that MTs expression in tumorous tissue is related to tumor type and origin, differentiation status and histological grade, which all can affect tumor aggressiveness and prognosis [ 34 ].…”

A systematic review and meta-analysis of cross-reactivity of antibodies induced by H7 influenza vaccine

“…If there was some missing data, the original authors were contacted for additional information on unreported data. For the results of antibody titers 37,38 and fold changes of antibody titers 39 displayed as images without digital data, images were imported into digital software (Engauge Digitizer 4.1) 40 to convert the outlines into x and y coordinates. Consequently, the values of the antibody titers or fold changes were displayed and then exported into Excel files.…”