Downregulation of NDUFB6 due to 9p24.1‐p13.3 loss is implicated in metastatic clear cell renal cell carcinoma

Abstract

This study was conducted to clarify the genomic profiles of metastatic clear cell renal cell carcinomas (ccRCCs) and identify the genes responsible for development of metastasis. We analyzed the genomic profiles of 20 cases of primary ccRCC and their corresponding metastases using array-based comparative genomic hybridization, and identified 32 chromosomal regions in which gene copy number alterations were detected more frequently in metastases than in the primary tumors. Among these 32 regions, 9p24.1-p13.3 loss was the most statistically significant alteration. Furthermore, we found that patients with 9p24.1-p13.3 loss in primary tumors exhibited significantly lower rates of recurrence-free and cancer-specific survival, suggesting that 9p loss in the primary tumor is a potential biomarker predicting early recurrence of metastasis. Interestingly, the genomic profiles of primary tumors with 9p loss resembled those of their corresponding metastases, though 9p loss was accumulated in the metastases derived from the primary tumors without 9p loss. Comparison of the mRNA expression levels revealed that 2 of 58 genes located at 9p24.1-p13.3 were downregulated due to gene copy number loss in ccRCCs. An overexpression study of these two genes in ccRCC cell lines revealed that downregulation of NDUFB6 due to loss at 9p24.1-p13.3 may confer a growth advantage on metastatic ccRCC cells. These results were confirmed by analyzing the data of 405 cases of ccRCC obtained from The Cancer Genome Atlas (TCGA). On the basis of our present data, we propose that NDUFB6 is a possible tumor suppressor of metastatic ccRCCs.

Identification and functional annotation of metabolism‐associated lncRNAs and their related protein‐coding genes in gastric cancer

“…Association analysis with clinicopathological features found that NDUFB6 may be a new biomarker of metastasis (Table 1). A recent study showed that NDUFB6 is a possible tumor suppressor of metastatic clear cell renal cell carcinomas (Narimatsu et al, 2015). NDUFB6, a component of respiratory chain complex I (RCI), is located in the mitochondria (Loublier et al, 2011) and plays an important role in electron transfer activity (Dieteren et al, 2011).…”

“…NDUFB6, a component of respiratory chain complex I (RCI), is located in the mitochondria (Loublier et al, 2011) and plays an important role in electron transfer activity (Dieteren et al, 2011). RCI dysfunction may contribute to tumor progression by enhancing the metastatic potential of tumor cells (Narimatsu et al, 2015). Clinical study has indicated that downregulation of NDUFB6 was implicated in poor prognosis of clear cell renal cell carcinomas (Narimatsu et al, 2015).…”

“…RCI dysfunction may contribute to tumor progression by enhancing the metastatic potential of tumor cells (Narimatsu et al, 2015). Clinical study has indicated that downregulation of NDUFB6 was implicated in poor prognosis of clear cell renal cell carcinomas (Narimatsu et al, 2015).…”

Transcriptome analysis of human colorectal cancer biopsies reveals extensive expression correlations among genes related to cell proliferation, lipid metabolism, immune response and collagen catabolism

“…The identification of highly connected potential hub genes from the gene co-expression network should facilitate the identification of candidate biomarkers and therapeutic targets for colorectal cancer. Among 10 putative hub genes (Table 1 , Figure 7 ), all 5 upregulated hub genes have been identified as oncogenes [ 40 , 53 – 59 ], and all 5 downregulated hub genes have been identified as tumor suppressor genes [ 60 – 64 ]. MTHFD1L is the only hub gene which has both positive and negative correlations with genes pertaining to cell cycle and lipid metabolism respectively (Figure 7A ).…”

Downregulation of WDR20 due to loss of 14q is involved in the malignant transformation of clear cell renal cell carcinoma

“…Primary tumors of RCC were surgically resected at Oita University Hospital and Oita Red Cross Hospital (Oita, Japan) and diagnosed histopathologically as described previously (Table S1). Use of the tissue samples for all experiments was approved by the Oita University Ethics Committee (approval no.…”