ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2024; 15(4):939-954. doi:10.7150/jca.87880 This issue Cite
Research Paper
Zinc Transporters Serve as Prognostic Predictors and their Expression Correlates with Immune Cell Infiltration in Specific Cancer: A Pan-cancer Analysis
1. School of Pharmacy, Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.
2. Department of Gastrointestinal & Pancreatic Surgery, Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, the Second Clinical College of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.
3. Department of Traditional Chinese Medicine, Hangzhou Shangcheng District People's Hospital, Hangzhou, China.
* These authors contributed equally to this work as first authors.
Abstract
The disruption of zinc (Zn) homeostasis has been implicated in cancer development and progression through various signaling pathways. Maintaining intracellular zinc balance is crucial in the context of cancer. Human cells rely on two families of transmembrane transporters, SLC30A/ZNT and SLC39A/ZIP, to coordinate zinc homeostasis. While some ZNTs and ZIPs have been linked to cancer progression, limited information is available regarding the expression patterns of zinc homeostasis-related genes and their potential roles in predicting prognosis and developing therapeutic strategies for specific cancers. In this study, a systematic analysis was conducted to examine the expression of all genes from the SLC30A and SLC39A families at both mRNA and protein levels across different cancers. As a result, three SLC39A genes (SLC39A1, SLC39A4, and SLC39A8) were found to be significantly dysregulated in specific cancers, including cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), liver hepatocellular carcinoma (LIHC), pancreatic adenocarcinoma (PAAD), and kidney renal papillary cell carcinoma (KIRP). Moreover, the dysregulation of these genes was tightly associated with the prognosis of patients with those cancers. Furthermore, we found that the gene SLC39A8 exhibited the lowest mutation frequency in KIRP, whereas mutations in SLC39A4 were found to significantly impact overall survival (OS), disease-free (DF), and progress-free survival (PFS) in cancer patients, particularly in those with PAAD. Additionally, immune infiltration analysis revealed that SLC39A1, SLC39A4, and SLC39A8 may function as immune regulators in cancers. This provides new insights into understanding the complex relationship between zinc homeostasis and cancer progression.
Keywords: trace element zinc, SLC30A, SLC39A, cancer prognosis, immune infiltration
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