Comprehensive analysis of the effects of the cuprotosis-associated gene SLC31A1 on patient prognosis and tumor microenvironment in human cancer

Our plain-English summary of Comprehensive analysis of the effects of the cuprotosis-associated gene SLC31A1 on patient prognosis and tumor microenvironment in human cancer, by G. Zhang, N. Wang, S. Ma, et al (Translational Cancer Research, 2024).

The study

• Authors: G. Zhang, N. Wang, S. Ma, P. Tao, H. Cai
• Journal: Translational Cancer Research
• Published: 2024;13(2):714-737
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Solute carrier family 31 (copper transporter), member 1 (SLC31A1) is a key factor in maintaining intracellular copper concentration and an important factor affecting cancer energy metabolism. Therefore, exploring the potential biological function and value of SLC31A1 could provide a new direction for the targeted therapy of tumors.

Methods: This study assessed gene expression levels, survival, clinicopathology, gene mutations, methylation levels, the tumor mutational burden (TMB), microsatellite instability (MSI), and the immune cell infiltration of SLC31A1 in pan-cancer using the Tumor Immune Estimation Resource 2.0 (TIMER2.0), Gene Expression Profiling Interactive Analysis (GEPIA), University of Alabama at Birmingham CANcer (UALCAN) data analysis portal, and cBioPortal databases. To further understand the potential biological mechanisms of SLC31A1 in different cancers, single-cell level sequencing and a Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) enrichment analysis of SLC31A1 were also performed. Finally, real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB) were used to validate the expression of SLC31A1 in cancers, such as gastric cancer.

Results: SLC31A1 was expressed in most cancer tissues. In kidney renal clear cell carcinoma (KIRC), the high expression of SLC31A1 was associated with good overall survival (OS), while in adrenocortical carcinoma (ACC), breast invasive carcinoma (BRCA), lower grade glioma (LGG), mesothelioma (MESO), and skin cutaneous melanoma (SKCM), the low expression of SLC31A1 was associated with good OS. The highest frequency of SLC31A1 amplification was observed in ACC. In addition, missense mutations accounted for a major portion of the mutation types. The truncation mutation S105Y may be a putative cancer driver. SLC31A1 affected methylation levels in cancer and was associated with the TMB, MSI, and the level of infiltration of various immune cells. Additionally, the single-cell sequencing results showed that SLC31A1 was associated with multiple biological functions in cancer. Finally, the SLC31A1 enrichment analysis revealed that the SLC31A1-related genes were mainly enriched in the mitochondrial matrix and envelope vesicles. The RT-qPCR and WB results were consistent with the predicted results.

Conclusions: SLC31A1 may be a potential target related to cancer energy metabolism and may have prognostic value.

2024 Translational Cancer Research. All rights reserved.

In plain English

This study did not examine asbestos. The authors used public cancer databases, mainly The Cancer Genome Atlas, to study SLC31A1, a gene that carries copper into cells, across 33 cancer types. Mesothelioma was one of them; the article does not say whether pleural or peritoneal. The authors also measured the gene in liver, gastric and colon cancer cell lines in the laboratory. In mesothelioma, low SLC31A1 expression was associated with better overall survival and better disease-free survival. The same overall-survival pattern was reported for several other cancers, while in kidney renal clear cell carcinoma high expression was associated with better overall survival. In mesothelioma, SLC31A1 expression was positively correlated with stromal and immune cell scores and negatively correlated with B cell and natural killer cell infiltration. In the laboratory, mRNA results matched the database predictions for liver and gastric cancer cells but not for colon cancer cells. The authors concluded that SLC31A1 may be a potential predictive target. They stated that their biggest limitation was being unable to validate the findings in tissue.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Bioinformatics analysis of public online cancer databases (pan-cancer), with laboratory validation in cell lines by RT-qPCR and western blotting
• Who was studied: Tumor and normal tissue data for 33 cancer types from The Cancer Genome Atlas and related databases, including mesothelioma (MESO). The TIMER2.0 figure lists 87 mesothelioma tumors. Laboratory work used liver, gastric and colon cancer cell lines and corresponding normal cell lines.
• Exposure: No asbestos or other fiber exposure was studied. The factor examined was the expression, genetic alteration and methylation of the copper-transporter gene SLC31A1.
• Main results:
  • In kidney renal clear cell carcinoma, high SLC31A1 expression was associated with good overall survival. In adrenocortical carcinoma, breast invasive carcinoma, lower grade glioma, mesothelioma and skin cutaneous melanoma, low expression was associated with good overall survival.
  • Low SLC31A1 expression was associated with good disease-free survival in adrenocortical carcinoma, lower grade glioma and mesothelioma.
  • SLC31A1 genetic alterations were reported as positively correlated with overall survival in several cancers, including mesothelioma.
  • SLC31A1 expression was positively correlated with stromal and immune cell scores in five cancers, including mesothelioma.
  • In mesothelioma, among other cancers, SLC31A1 expression was negatively correlated with B cell infiltration and with natural killer cell infiltration.
  • Across cancers, SLC31A1 amplification was most frequent in adrenocortical carcinoma.
  • At the mRNA level, SLC31A1 was low in liver cancer cells, high in gastric cancer cells and low in colon cancer cells, each compared with corresponding normal cells.
• The authors' conclusion: The authors concluded that SLC31A1 may influence tumor patients' prognosis through energy metabolism, coated vesicles and the immune microenvironment, and may be a potential predictive target.
• Limitations the authors state:
  • The authors could not validate SLC31A1 expression in tissue samples, which they called the biggest limitation of their study.
  • Laboratory results for colon cancer cells were opposite to the database predictions. The authors suggested cell heterogeneity or differences between tissue and cell levels as possible causes.

Topics

Medical terms in this study, explained in our Lexicon: Prognosis, Tumor Microenvironment, Targeted Therapy, Tumor Mutational Burden (TMB), Microsatellite Instability (MSI-H), Stomach Cancer, Carcinoma, Overall Survival.

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