High expression of patched homolog-1 messenger RNA and glioma-associated oncogene-1 messenger RNA of sonic hedgehog signaling pathway indicates a risk of postresection recurrence of hepatocellular carcinoma.
BACKGROUND
Hepatocellular carcinoma (HCC) has a high recurrence rate after resection. Abnormal activation of the sonic hedgehog (SHH) signaling pathway contributing to the carcinogenesis of some organs had been reported. We hypothesize that activation of SHH pathway contributes to the recurrence of HCC after surgical resection.


METHODS
In a prospective study, from January 2006 to June 2010, a total of 50 consecutive patients with HCC after curative resection were enrolled. The ratio of the expression of messenger RNA (mRNA) of SHH, patched homolog-1 (PTCH-1) and glioma-associated oncogene-1 (GLI-1) between HCC tissues and the paired noncancerous liver tissues were measured. Both the clinicopathologic characteristics and these ratios were compared between those with recurrence and those without recurrence. They were also compared between those with and without survival.


RESULTS
There was a statistically significant correlation among the ratios of PTCH-1 mRNA and serum AFP level (p = 0.045), tumor size (p = 0.001), vascular permeation (p = 0.043) and tumor, node, metastasis staging system (TNM) stage (p = 0.003). A borderline significant correlation was found among ratios of GLI-1 mRNA and tumor size (p = 0.062) and TNM stage (p = 0.051). There was no such significant correlation between SHH mRNA and any parameter. Both the ratios of PTCH-1 mRNA and GLI-1 mRNA significantly adversely affected recurrence (p = 0.003 and 0.005, respectively) and survival (p < 0.001 and <0.001, respectively).


CONCLUSIONS
Expression of PTCH-1 mRNA and GLI-1 mRNA in HCC tissues is a potential biomarker to predict postresection disease recurrence.
Department of Surgery, Far Eastern Memorial Hospital, Taipei, Taiwan.
Kuo-Shyang
KS
Jeng
I-Shyan
IS
Sheen
Wen-Juei
WJ
Jeng
Chien-Chu
CC
Lin
Chien-Kuan
CK
Lin
Jui-Chih
JC
Su
Ming-Che
MC
Yu
Hsin-Yi
HY
Fang
D014408:Biomarkers, Tumor / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D053823:Hedgehog Proteins / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D009367:Neoplasm Staging; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011183:Postoperative Complications; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics*; D000071676:Zinc Finger Protein GLI1
D014408:Biomarkers, Tumor; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C509239:SHH protein, human; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1