Low CADM2 expression predicts high recurrence risk of hepatocellular carcinoma patients after hepatectomy.
OBJECTIVE
To investigate the expression and clinical significance of CADM2 in hepatocellular carcinomas (HCC).


METHODS
The level of expression of CADM2 mRNA was assessed in frozen tumor specimens and adjacent noncancerous tissues from 30 HCC patients by real-time PCR. The protein level was determined by immunohistochemistry on a tissue microarray containing tumor and adjacent noncancerous tissues from 234 HCC patients. Clinicopathological characteristics associated analysis was performed through SPSS18 .


RESULTS
CADM2 was strikingly down regulated in HCC. CADM2 expression was associated with differentiation (P = 0.000), serum alpha-fetoprotein (P = 0.003), vascular invasion (P = 0.001), and hepatitis B surface antigen (HBsAg, P = 0.038). Furthermore, patients with low CADM2 expression had significantly poorer recurrence-free survival (RFS) (40.8 and 34.2 % vs. 56.3 and 50.1 % in 3- and 5-year RFS, respectively, P = 0.005). Subgroup analysis revealed that the difference in RFS between groups with low- and high-CADM2 expression still existed among patients belonging to stage 0 or A of BCLC staging system (P = 0.008), patients with tumor ≤5 cm in size (P = 0.013), and alpha-fetoprotein-negative patients (P = 0.003). Moreover, low expression was more frequently observed in the early recurrence group (within 2 years, P = 0.007). Further multivariate Cox regression analysis indicated that CADM2 expression level, tumor size, tumor number, vascular invasion, HBsAg were independent risk factors for HCC recurrence.


CONCLUSIONS
CADM2 serves as a novel predictor of RFS in HCC patients after curative resection.
The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200438, China.
Sen
S
Yang
Hong-Li
HL
Yan
Qi-Fei
QF
Tao
Sheng-Xian
SX
Yuan
Guan-Nan
GN
Tang
Yuan
Y
Yang
Li-Li
LL
Wang
Yi-Liang
YL
Zhang
Shu-Han
SH
Sun
Wei-Ping
WP
Zhou
D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D006498:Hepatectomy; D057166:High-Throughput Screening Assays; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; C556123:CADM2 protein, human; D015815:Cell Adhesion Molecules; D012333:RNA, Messenger