Increase in NETO2 gene expression is a potential molecular genetic marker in renal and lung cancers

Abstract

Multiple changes in the genome, transcriptome, and proteome are frequent in cancer cells. A search for molecular markers based on DNA, mRNA, or proteins is a main method to develop early specific diagnostics for cancer. While universal markers are still unavailable, similar trends are known for the expres sion patterns of particular genes in certain epithelial tumors. A bioinformatic screening of transcriptomic databases identified the NETO2 gene as a new potential promising marker of renal cancer. A substantial increase in NETO2 mRNA level was detected in 90% clear cell renal cell carcinomas, 70% of non small cell lung cancers, and 50% of papillary renal cancers by real time PCR. The NETO2 mRNA level was increased to a lesser extent in cervical carcinoma and colon cancer and tended to decrease in cancer of the stomach. The NETO2 gene, which codes for a membrane glycoprotein with an unclear function, was assumed to pro vide a new promising marker for early diagnosis in renal cancer and non small cell lung cancer.

Upregulation of NETO2 expression correlates with tumor progression and poor prognosis in colorectal carcinoma

“…Using real-time qPCR and Western blot analysis, we found that NETO2 was frequently overexpressed in primary CRC samples at both the mRNA and protein levels. Our results are consistent with the previous findings of Oparina et al at the mRNA level [ 16 ]. Of note, we observed a significant increase in NETO2 mRNA level (over 2-fold) in 52.6 % (30/57) of the cancerous specimens tested, whereas Oparina et al reported that only 40 % (4/10) of colon cancer samples showed substantially increased expression of NETO2 mRNA.…”

“…In addition, Horak et al found that it could be downregulated by the metastasis suppressor gene Nm23-H1 in breast carcinoma cell lines [ 23 ]. Notably, Oparina et al recently demonstrated that the NETO2 mRNA is frequently overexpressed in a number of human neoplasms and might be a tool to support the early diagnosis of renal and lung carcinomas [ 16 ]. These findings indicate that NETO2 may have potential significance in cancer pathobiology.…”

“…In addition, NETO2 has been demonstrated to be a K + –Cl − cotransporter (KCC2) interacting protein and required for neuronal Cl − regulation in hippocampal neurons [ 15 ]. Although NETO2 was initially believed to be a brain-specific protein [ 9 , 11 ], a recent study conducted by Oparina et al revealed that NETO2 mRNA expression was also detectable in a variety of normal non-neural tissues and upregulated in several types of cancers including renal, lung, colon and cervical carcinomas [ 16 ]. Moreover, they provided evidence that the NETO2 mRNA level could be a potential marker for early diagnosis in renal cancer and non-small cell lung cancer.…”

Comprehensive, integrated, and phased whole-genome analysis of the primary ENCODE cell line K562

“…4D), involving two overlapping inversions (62 and 125 kb) and a tandem duplication (163 kb). These events affect ORC6, MYLK3, RHBDF1 (previously known as C16orf8), and NETO2, which has recently been identified as a cancer marker gene (Oparina et al 2012;Hu et al 2015). This rearrangement resides on the nonduplicated haplotype of this triploid region.…”

Untitled

“…Numerous genetic and epigenetic changes, occurring in ccRCC, effect transcription of many genes and lead to alterations in different metabolic pathways. [3][4][5][6][7][8] Deregulation of metabolic pathways in ccRCC determines its aggressive phenotype. [9] Understanding the molecular mechanisms leading to altered metabolic pathways in ccRCC could provide novel targets for therapies and diagnostic biomarkers.…”