The role of RNA binding motif on Y Chromosome (RBMY) expression in the outcome of human hepatocellular carcinoma
Date Issued
2014
Date
2014
Author(s)
Kao, Pei-chi
Abstract
Background and aim:
Liver cancer remains one of the commonest cancers worldwide. Hepatocellular carcinoma (HCC) and hepatoblastoma (HB) are two major types of human liver cancer. Chronic infection with hepatitis B virus (HBV) has been closely associated with the development of HCC, which was found in around 80% of adult HCC and nearly 100% of childhood HCC. HB accounted for 90% of primary malignant liver tumor in children less than 5 years of age in Taiwan. Male predominance had been observed in both adult and childhood HCC, especially HBV-related HCC, with man to woman sex ratio ranging from 2:1 to 7:1. HB occurs in males significantly more frequently than it does in females and the reason remains obscure.
The RNA-binding motif gene on Y chromosome ( RBMY gene), encoding a male germ cell-specific RNA binding protein associated with spermatogenesis, was found integrated by HBV DNA in a childhood HCC tissue. The RBMY transcripts, expressed exclusively in the testis of normal people, were detected by reverse transcription – polymerase chain reaction in 32 (36%) out of 90 male HCCs and in 4 (67%) of 6 male HB in a previous study. Nontumor liver counter parts were all negative for RBMY transcripts. Besides, previous study also revealed liver-specific RBMY transgenic mice developed hepatic pre-cancerous lesions, adenoma, and HCC. This study was aimed to evaluate the expression of RBMY in HCC patients to determine if a correlation between RBMY expression and the survival outcome existed.
Methods:
We enrolled total 197 male patients of hepatocellular carcinoma, from National Taiwan University Hospital as the baseline-study group. The HCC liver tissues were collected from the surgery and they were dealt with frozen embedded. To elaborate our model further, an additional cohort of 75 male patients of hepatocellular carcinoma, from the same hospital was enrolled as the validation group. Their liver tissues were collected from the surgery and dealt with paraffin embedded. Clinical data and pathologic findings were obtained from the medical records, including clinical presentation, American joint committee on cancer (AJCC) pathologic staging system, tumor grading, and survival condition. We checked the RBMY protein expression status by immunohistochemistry assessment. We evaluated the correlation between the clinical presentation and survival condition with RBMY protein expression.
Results:
RBMY protein was expressed in 143 (72.6%) of baseline-study group, including two patterns of RBMY protein distribution within HCC hepatocytes, including nucleus and cytoplasm. RBMY protein expression correlated with high grade AJCC staging (p= 0.034) and also contributed to poor prognosis trend, especially those with RBMY protein expression within the cytoplasm of hepatocytes (p= 0.0027). We confirmed the similar results in the validation group.
Conclusions:
RBMY protein expression correlated with higher AJCC tumor stage and was a significant prognostic factor for human hepatocellular carcinoma.
Subjects
肝細胞癌
RBMY
預後
SDGs
Type
thesis
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