Loss of Heterozygosity at D8S298 Is a Predictor for Long-term Survival of Patients with Tumor-Node-Metastasis Stage I of Hepatocellular Carcinoma

Abstract

Purpose: Our previous studies have shown that chromosome 8p deletion correlates with metastasis of hepatocellular carcinoma (HCC). This study was to determine whether 8p deletion could be used in predicting the prognosis of patients with HCC, particularly in those with early stage of HCC. Experimental Design: A total of 131 patients with tumor-node-metastasis (TNM) stage I of HCC who underwent curative liver resection were enrolled. Loss of heterozygosity (LOH) was examined using 10 microsatellite markers at chromosome 8p, as well as 14 microsatellites at chromosome 1p, 17p, 4q, 13q, and 16q, and their association with 5-year overall survival (OS) and disease-free survival (DFS) of patients was analyzed. Results: In the entire cohort of patients, the mean LOH frequency at these 24 loci was 43.2%; LOH frequencies at D8S298 and D1S199 were 31.5% and 33.7%, respectively. LOH at D8S298 was associated with a worse 5-year OS (P = 0.008) and DFS (P = 0.038) in patients withTNM stage I of HCC. Likewise, the patients with LOH at D1S199 had a worse 5-year OS (P < 0.001) and DFS (P = 0.014) compared with those without LOH at D1S199. In multivariate analyses, LOH at D8S298 was an independent predictor of decreased DFS (hazard ratio, 0.372; 95% 95% confidence interval, 0.146-0.948; P = 0.038), whereas LOH at D1S199 was an independent predictor of decreased OS (hazard ratio, 0.281; 95% confidence interval, 0.123-0.643; P = 0.003). Conclusions: LOH at D8S298 and D1S199 is independently associated with a worse survival in patients with TNM stage I of HCC after curative resection and could serve as novel prognostic predictors for this subgroup of patients.

Human Leukocyte Antigen-G Protein Expression Is an Unfavorable Prognostic Predictor of Hepatocellular Carcinoma following Curative Resection

“…Albeit HLA-G group was only significant in OS by multivariate analysis in all patient population, its independent power was enhanced in predicting both survival and recurrence in early HCC patients indicated by a sharply increased HR (3.145 versus 1.987) for death and a gained significance for recurrence. Its independent prognostic significance in early HCC patients is of clinical importance because among intermediate to advanced stages of HCC, multinodularity (37) and the presence of vascular invasion (38) have already been well-established adverse prognostic predictors after liver resection, while the prognosis of earlystage HCC is far from homogenous and its lack of those clinicopathologic indicators and existing classification systems have shown limitations on precise prediction of patients' outcome (39). With the shift of more patients diagnosed at earlier stages, establishment of novel prognostic markers is more important for early than advanced stages and our results meet this requirement to refine the prognosis of early-stage patients.…”

Association of Specific Genotypes in Metastatic Suppressor HTPAP with Tumor Metastasis and Clinical Prognosis in Hepatocellular Carcinoma

“…Our previous studies demonstrating that chromosome 8p deletion was associated with hepatocellular carcinoma (HCC) metastasis (1)(2)(3)(4) identified HTPAP gene as a suppressor of in vitro invasion and in vivo lung metastasis of HCC (5). The official symbol of the HTPAP gene is phosphatidic acid phosphatase type 2 domain containing 1B (PPAPDC1B).…”

Role of ING Family Genes in Head and Neck Cancer and Their Possible Applications in Cancer Diagnosis and Treatment

“…In another report, allelic loss at 3p and 9p21 was related with elevated risk of malignant transformation of the premalignant lesions in head and neck cancer [90]. Similarly LOH at 8p was a predictor for long-term survival in hepatocellular carcinoma [91].…”