Identification of Prognostic Organic Cation and Anion Transporters in Different Cancer Entities by In Silico Analysis

Abstract

The information derived from next generation sequencing technology allows the identification of deregulated genes, gene mutations, epigenetic modifications, and other genomic events that are associated with a given tumor entity. Its combination with clinical data allows the prediction of patients’ survival with a specific gene expression pattern. Organic anion transporters and organic cation transporters are important proteins that transport a variety of substances across membranes. They are also able to transport drugs that are used for the treatment of cancer and could be used to improve treatment. In this study, we have made use of publicly available data to analyze if the expression of organic anion transporters or organic cation transporters have a prognostic value for a given tumor entity. The expression of most organic cation transporters is prognostic favorable. Within the organic anion transporters, the ratio between favorable and unfavorable organic anion transporters is nearly equal for most tumor entities and only in liver cancer is the number of unfavorable genes two times higher compared to favorable genes. Within the favorable genes, UNC13B, and SFXN2 cover nine cancer types and in the same way, SLC2A1, PLS3, SLC16A1, and SLC16A3 within the unfavorable set of genes and could serve as novel target structures.

The Expression Profiles of ADME Genes in Human Cancers and Their Associations with Clinical Outcomes

“…The influx transporters are involved in the uptake of anticancer drugs into cells, and therefore their high intratumoral expression may increase therapeutic efficacy and improve cancer patient survival [ 61 , 62 , 63 , 64 ]. Indeed, we showed here that four influx transporters (SLC15A2, SLC22A1, SLC22A2, SLC22A6) whose high intratumoral expression was correlated only with favourable OS ( Figure 4 B).…”

Catechol-O-methyl transferase suppresses cell invasion and interplays with MET signaling in estrogen dependent breast cancer

“…From these, sideroflexin-2 (SFXN2) is an evolutionary conserved protein involved in mitochondrial iron metabolism by regulating heme biosynthesis 21 . SFXN2 was later observed as an prognostic factor in renal, urothelial, cervical, and liver cancer and its high expression was associated with a significantly longer overall survival probability in the PANCAN cohort with more than 12,800 samples derived from 17 different tumors 22 . Furthermore, LCP1 gene product representing plastin-2/L-plastin protein was downregulated in MCF7-COMT cells; this protein was observed to accompany tumorigenesis in malignant cells and was connected to cell migration and metastasis 23 .…”

In Vitro and In Silico Studies on Cytotoxic Properties of Oxythiamine and 2′-Methylthiamine

“…That may explain the lower cytotoxic effect of thiamine antimetabolites on tumor cells as compared to fibroblasts. On the other hand, the enhanced expression of OCT1 is correlated with less differentiation toward the kidney tumor cells and is the positive prognostic value in the case of various liver cancers due to involvement of this protein in cytostatics transport [47][48][49]. ThiT is the S-component of the thiamine-specific energy coupling factor ECF derived from Lactococcus lactis, which is a known prokaryotic thiamine transporter that has been used in the studies of the transport of various thiamine derivatives into bacterial cells [50][51][52].…”