Do the expressions of gap junction gene connexin messenger RNA in noncancerous liver remnants of patients with hepatocellular carcinoma correlate with postoperative recurrences?
OBJECTIVE
To investigate whether the changes of gap junction gene connexin messenger RNA in the noncancerous liver tissue of patients with hepatocellular carcinoma (HCC) could play a significant role in its postresection recurrence.


METHODS
Seventy-nine consecutive patients having undergone curative resection for HCC entered this study. Using a reverse-transcription polymerase chain reaction (RT-PCR)-based assay, connexin (Cx) 26, connexin (Cx) 32 and connexin (Cx) 43 mRNAs were determined prospectively in noncancerous liver tissues from these 79 patients and in the liver tissues from 15 controls. The correlations between connexin mRNA expression and the clinicopathological variables and outcomes (tumor recurrence and recurrence related mortality) were studied.


RESULTS
Compared with liver tissues of control patients, the expression of Cx 32 mRNA in noncancerous liver tissues was significantly lower (mean: 0.715 vs control 1.225, P<0.01), whereas the decreased Cx 26 mRNA (mean: 0.700 vs of control 1.205, P>0.05) and increased Cx 43 mRNA (mean: 0.241 vs control 0.100, P>0.05) had no statistical significance. We defined the value of Cx 32 mRNA or Cx 26 mRNA below 0.800 as a lower value. By multivariate analysis for noncancerous livers, a lower value of Cx 32 mRNA correlated significantly with a risk of HCC recurrence and recurrence-related mortality. The lower value of Cx 26 mRNA did not correlate with recurrence and mortality. The increased value of Cx43 mRNA also did not correlate with postoperative recurrence and recurrence-related mortality. By multivariate analysis, other significant predictors of HCC recurrence included vascular permeation, cellular dedifferentiation, and less encapsulation. The other significant parameter of recurrence related mortality was vascular permeation.


CONCLUSIONS
The decreased expression of Cx 32 mRNA in noncancerous liver tissues plays a significant role in the prediction of postoperative recurrence of HCC.
Sheen
I-Shyan
IS
Division of Hepatogastroenterology, Chang Gung Memorial Hospital, Taipei, Taiwan, China.
Jeng
Kuo-Shyang
KS
Shih
Shou-Chuan
SC
Kao
Chin-Roa
CR
Wang
Po-Chuan
PC
Chen
Chih-Zen
CZ
Chang
Wen-Hsing
WH
Wang
Horng-Yuan
HY
Shyung
Li-Rung
LR
D001483:Base Sequence; D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D017630:Connexins / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D017629:Gap Junctions / Q000235:genetics; D006470:Hemorrhage; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D012333:RNA, Messenger / Q000235:genetics*; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D017630:Connexins; D017931:DNA Primers; D012333:RNA, Messenger