Correlation Between Poor Prognosis and Lower TPPP Gene Expression in Hepatocellular Carcinoma.

Anticancer research ·Vol. 36 ·No. 9 ·2016-00-00 ·Pages 4639-45

Inokawa Y, Sonohara F, Kanda M, Hayashi M, Nishikawa Y, Sugimoto H, Kodera Y, Nomoto S

Abstract

Post-resection recurrence of hepatocellular carcinoma (HCC) tends to derive from multicentric origins, which indicates that the background liver microenvironment affects carcinogenesis. We obtained control liver samples [super normal (SN)] from 11 patients with secondary metastatic liver malignancies and used expression and methylation arrays to compare them with non-cancerous liver tissue from a patient with typical HCC with chronic hepatitis C (corresponding normal (CN)]. The expression array showed that gene expression of tubulin polymerization-promoting protein (TPPP) was lower in CN compared with SN. The methylation array showed a greater TPPP methylation index for CN than for SN. Transcripts of TPPP differed significantly among SN (n=11), CN (n=179), and tumor tissue of HCC (n=179) (median of 116, 4.60, and 2.63, respectively, p<0.001). Multivariate analysis showed lower TPPP expression in tumor than in normal tissue (ratio <0.3, n=57) to independently predict poor overall survival (p=0.031). Significantly lower TPPP expression was found in HCC and CN tissue compared to SN and indicated poor prognosis.

Keywords

Background liver TPPP/p25 hepatocellular carcinoma methylation multi-array analysis

MeSH Terms

Adult Aged Aged, 80 and over Carcinoma, Hepatocellular/diagnosis,metabolism,mortality Cell Line, Tumor DNA Methylation Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Hepatitis C/complications,metabolism Humans Liver/metabolism,pathology Liver Neoplasms/diagnosis,metabolism,mortality Male Middle Aged Multivariate Analysis Neoplasm Metastasis Nerve Tissue Proteins/metabolism Oligonucleotide Array Sequence Analysis Prognosis Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Treatment Outcome Young Adult

Chemicals

Nerve Tissue Proteins TPPP protein, human

Authors & Affiliations

8 authors, click to expand affiliations / ORCID

Inokawa Yoshikuni

Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan Department of Surgery, Aichi Gakuin University School of Dentistry, Nagoya, Japan.

Sonohara Fuminori

Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan Department of Surgery, Aichi Gakuin University School of Dentistry, Nagoya, Japan.

Kanda Mitsuro