Identification and Validation of Prognostic Related Hallmark ATP-Binding Cassette Transporters Associated With Immune Cell Infiltration Patterns in Thyroid Carcinoma

Abstract

ATP-binding cassette (ABC) transporters are a large superfamily of membrane proteins that facilitate the translocation of heterogeneous substrates. Studies indicate that ABC transporters may play important roles in various carcinomas. However, the correlation between ABC transporters and immunomodulation in thyroid carcinoma (TC), as well as the prognoses for this disease, is poorly understood.TC data from The Cancer Genome Atlas (TCGA) database were used to identify prognostic hallmark ABC transporters associated with immune cell infiltration patterns via multiple bioinformatic analyses. Thereafter, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate the expression of these selected hallmark ABC transporters in both TC and para-cancerous thyroid tissues. Of a total of 49 ABC transporters, five (ABCA8, ABCA12, ABCB6, ABCB8, and ABCC10) were identified as hallmark ABC transporters. All five were differentially expressed in TC and associated with the relapse-free survival rates of patients with TC. Immunoregulation by these five hallmark ABC transporters involved the modulation of various aspects of immune cell infiltration, such as hot or cold tumor subsets and the abundances of infiltrating immune cells, as well as specific immunomodulators and chemokines. Besides the diverse significantly correlated factors, the five hallmark ABC transporters and correlated genes were most highly enriched in plasma membrane, transporter activity, and transmembrane transport of small molecules. In addition, many chemicals, namely bisphenol A and vincristine, affected the expression of these five transporters. The qRT-PCR results of collected TC and para-cancerous thyroid tissues were consistent with those of TCGA. The findings in this study may reveal the role played by these five hallmark ABC transporters in regulating immune cell infiltration patterns in TC as well as the molecular mechanisms underlying their functions, leading to a better understanding of their potential prognostic and immunotherapeutic values.