Systematic pan-cancer analysis identifies SLC31A1 as a biomarker in multiple tumor types

Our plain-English summary of Systematic pan-cancer analysis identifies SLC31A1 as a biomarker in multiple tumor types, by F.S. Kong, C.Y. Ren, R. Jia, et al (BMC Medical Genomics, 2023).

The study

• Authors: F.S. Kong, C.Y. Ren, R. Jia, Y. Zhou, J.H. Chen, Y. Ma
• Journal: BMC Medical Genomics
• Published: 2023;16(1):61
• Cited by: 29 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Solute Carrier Family 31 Member 1 (SLC31A1) has recently been identified as a cuproptosis-regulatory gene. Recent studies have indicated that SLC31A1 may play a role in colorectal and lung cancer tumorigenesis. However, the role of SLC31A1 and its cuproptosis-regulatory functions in multiple tumor types remains to be further elucidated.

Methods: Online websites and datasets such as HPA, TIMER2, GEPIA, OncoVar, and cProSite were used to extract data on SLC31A1 in multiple cancers. DAVID and BioGRID were used to conduct functional analysis and construct the protein-protein interaction (PPI) network, respectively. The protein expression data of SLC31A1 was obtained from the cProSite database.

Results: The Cancer Genome Atlas (TCGA) datasets showed increased SLC31A1 expression in tumor tissues compared with non-tumor tissues in most tumor types. In patients with tumor types including adrenocortical carcinoma, low-grade glioma, or mesothelioma, higher SLC31A1 expression was associated with shorter overall survival and disease-free survival. S105Y was the most prevalent point mutation in SLC31A1 in TCGA pan-cancer datasets. Moreover, SLC31A1 expression was positively correlated with the infiltration of immune cells such as macrophages and neutrophils in tumor tissues in several tumor types. Functional enrichment analysis showed that SLC31A1 co-expressed genes were involved in protein binding, integral components of the membrane, metabolic pathways, protein processing, and endoplasmic reticulum. Copper Chaperone For Superoxide Dismutase, Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha and Solute Carrier Family 31 Member 2 were copper homeostasis-regulated genes shown in the PPI network, and their expression was positively correlated with SLC31A1. Analysis showed there was a correlation between SLC31A1 protein and mRNA in various tumors.

Conclusions: These findings demonstrated that SLC31A1 is associated with multiple tumor types and disease prognosis. SLC31A1 may be a potential key biomarker and therapeutic target in cancers.

© 2023. The Author(s).

In plain English

This study was a computer analysis of public cancer databases, mainly The Cancer Genome Atlas (TCGA). It looked at SLC31A1, a gene that helps cells take up copper. The study did not look at asbestos or any other exposure. The authors compared how active the gene was in tumor and normal tissue across many cancer types, and whether its activity was linked to survival. Mesothelioma had 87 tumor samples but no normal-tissue samples for that comparison. The gene was more active in most tumor types than in matching normal tissue. In mesothelioma, adrenocortical carcinoma and low-grade glioma, higher gene activity was associated with worse overall survival and worse disease-free survival. For mesothelioma the p-values were 1.8 × 10 to the minus 5 for overall survival and 0.044 for disease-free survival. Gene activity also differed between mesothelioma stages. The most common mutation in the gene was S105Y. The authors concluded that SLC31A1 may be a potential biomarker and treatment target in cancers. They called their findings preliminary and said small samples for rare tumor types needed checking in independent patient groups.

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: Bioinformatic (computer-based) analysis of publicly available online cancer databases; no new patients or samples were collected
• Who was studied: Tumor and normal tissue data for many cancer types in TCGA and other public databases, including 87 mesothelioma tumor samples (no mesothelioma normal tissue listed); the article does not give dates or locations
• Exposure: No asbestos or environmental exposure was studied; the factor examined was the activity (expression) and mutation of the copper-transporter gene SLC31A1
• Main results:
  • SLC31A1 mRNA was higher in most tumor tissues than in corresponding normal tissues; mesothelioma had tumor samples only and was not part of this comparison
  • Higher SLC31A1 expression was associated with worse overall survival in several tumor types, including adrenocortical carcinoma (P = 0.0012) and mesothelioma (P printed as 1.8 × 10 to the minus 5)
  • Higher SLC31A1 levels were associated with worse disease-free survival in patients with adrenocortical carcinoma, low-grade glioma (P = 0.032) and mesothelioma (P = 0.044)
  • SLC31A1 expression differed significantly among pathological stages of adrenocortical carcinoma, KIRC and mesothelioma (all P less than 0.05)
  • S105Y was the most prevalent point mutation in SLC31A1 in TCGA tumor samples; uterine corpus endometrioid carcinoma had the highest alteration frequency (2.46%)
  • SLC31A1 expression was positively correlated with macrophage infiltration in several tumor types (bladder, colon, head and neck, KIRC, lung adenocarcinoma, lung squamous, pancreatic, thymoma); mesothelioma was not among those listed
  • Across all tumor samples, expression of the copper-related genes SLC31A2, PIK3CA and CCS was correlated with SLC31A1, with Spearman r of 0.31, 0.34 and −0.22 respectively
• The authors' conclusion: The authors concluded that SLC31A1 may be a potential key biomarker and therapeutic target in cancers, and that further experimental and clinical studies are warranted
• Limitations the authors state:
  • The authors described their findings as preliminary; sample sizes for some rare tumor types were relatively small, and the findings need to be validated in independent cohorts
  • The molecular function of SLC31A1 in tumor development still needs to be determined

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Biomarker, Lung Cancer, Carcinogenesis, Carcinoma, Mesothelioma, Overall Survival, Disease-Free Survival, Macrophage.

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