Toshiya Kamiyama, Masato Takahashi, Hideki Yokoo, Nozomi Kobayashi, Department of General Surgery, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan.
World J Gastroenterol. 2012 Jan 28;18(4):340-8. doi: 10.3748/wjg.v18.i4.340.
To investigate whether α-fetoprotein (AFP) and vascular endothelial growth factor receptor (VEGFR)-1 correlate with early recurrence of hepatoma/hepatocellular carcinoma (HCC).
From 2000 to 2005, 114 consecutive patients with HCC underwent primary curative hepatectomy. The mean age was 60.7 (8.7) years and 94 patients were male. The median follow-up period was 71.2 mo (range: 43-100 mo). Immediately prior to commencing laparotomy, 5 mL bone marrow was aspirated from the sternum and collected in citrate-coated test tubes. The initial 2 mL of bone marrow aspirate was discarded in each case. AFP mRNA and VEGFR-1 mRNA in the bone marrow and peripheral blood (BM- and PH-AFP mRNA and BM- and PH-VEGFR-1 mRNA, respectively) were measured by real-time quantitative reverse transcription polymerase chain reaction. As normal controls, VEGFR-1 mRNA in the bone marrow and peripheral blood was also measured in 11 living liver donors. These data were evaluated for any correlation with early recurrence, comparing clinical and pathological outcomes.
The cut-off value of the BM-AFP mRNA and PH-AFP mRNA level in patients with HCC was set at 1.92 × 10(-7) and zero, respectively, based on data from the controls. A total of 34 (29.8%) and six (5.4%) patients were positive for BM-AFP mRNA and PH-AFP mRNA, respectively. The BM-VEGFR-1 mRNA levels in all HCC patients were higher than those in the normal controls, and this was the case also for PH-VEGFR-1mRNA. The 25-percentile values for the BM- and PH-VEGFR-1 mRNA in HCC patients were used as the cut-off values for assigning the patients into two groups based on these transcript levels. The High group for BM- VEGFR-1 mRNA contained 81 (71.1%) HCC cases and the Low group was assigned 33 (28.9%) patients. These numbers for PH-VEGFR-1mRNA were 78 (75.0%) and 26 (25.0%), respectively. HCC recurred in 80 patients; in the remnant liver in 48 cases, in the remnant liver and remote tissue in 20, and in the remote tissue alone in 12. BM-AFP mRNA-positive cases showed a significantly higher rate of early recurrence (within 1 year of surgical treatment) compared with BM-AFP mRNA-negative patients (P = 0.0091). Patients were classified into four groups according to the level/status of their BM-VEGFR-1 and BM-AFP mRNA as follows: group A (n = 23), BM-VEGFR-1/BM-AFP mRNA = low/negative; group B (n = 57) high/negative; group C (n = 10) low/positive; group D (n = 24), high/positive. This classification was found to correlate with a recurrence of this disease within 1 year (P = 0.0228). The disease-free survival curve of group A was significantly better than that of groups B, C or D (P = 0.0437, P = 0.0325, P = 0.0225). No other classification (i.e., PH-VEGF-R1/BM-AFP, BM-VEGF-R1/PH-AFP, and PH-VEGF-R1/PH-AFP mRNA) showed such a correlation.
The evaluation of BM-AFP and BM-VEGFR-1 mRNA in patients with HCC may be a valuable predictor of disease recurrence following curative resection.
探讨甲胎蛋白（AFP）和血管内皮生长因子受体（VEGFR）-1 是否与肝癌/肝细胞癌（HCC）的早期复发相关。
2000 年至 2005 年，对 114 例 HCC 患者进行了根治性肝切除术。平均年龄为 60.7（8.7）岁，94 例为男性。中位随访时间为 71.2 个月（范围：43-100 个月）。在剖腹手术前，从胸骨抽吸 5mL 骨髓，并收集在柠檬酸盐涂层的试管中。在每种情况下，均丢弃初始的 2mL 骨髓抽吸物。通过实时定量逆转录聚合酶链反应测量骨髓和外周血中的 AFPmRNA 和 VEGFR-1mRNA（分别为 BM-和 PH-AFPmRNA 和 BM-和 PH-VEGFR-1mRNA）。作为正常对照，还测量了 11 位活体供肝者的骨髓和外周血中的 VEGFR-1mRNA。评估这些数据与早期复发的任何相关性，比较临床和病理结果。
根据对照数据，将 HCC 患者骨髓 AFPmRNA 和外周血 AFPmRNA 水平的截断值设定为 1.92×10(-7)和零。共有 34（29.8%）和 6（5.4%）例患者的 BM-AFPmRNA 和 PH-AFPmRNA 阳性。所有 HCC 患者的骨髓 VEGFR-1mRNA 水平均高于正常对照组，PH-VEGFR-1mRNA 也是如此。将 HCC 患者骨髓和外周血 VEGFR-1mRNA 的 25%百分位数值用作根据这些转录物水平将患者分为两组的截断值。BM-VEGFR-1mRNA 高组包含 81（71.1%）例 HCC 病例，低组分配 33（28.9%）例患者。对于 PH-VEGFR-1mRNA，这些数字分别为 78（75.0%）和 26（25.0%）。80 例 HCC 患者复发；48 例在残肝中，20 例在残肝和远处组织中，12 例在远处组织中。BM-AFPmRNA 阳性病例的早期复发（手术治疗后 1 年内）率明显高于 BM-AFPmRNA 阴性患者（P=0.0091）。根据 BM-VEGFR-1 和 BM-AFPmRNA 的水平/状态，患者分为以下四组：A 组（n=23），BM-VEGFR-1/BM-AFPmRNA=低/阴性；B 组（n=57），高/阴性；C 组（n=10），低/阳性；D 组（n=24），高/阳性。发现这种分类与 1 年内疾病复发相关（P=0.0228）。A 组的无病生存曲线明显优于 B、C 或 D 组（P=0.0437，P=0.0325，P=0.0225）。其他分类（即 PH-VEGF-R1/BM-AFP、BM-VEGF-R1/PH-AFP 和 PH-VEGF-R1/PH-AFPmRNA）均未显示出这种相关性。
评估 HCC 患者的 BM-AFP 和 BM-VEGFR-1mRNA 可能是预测根治性切除术后疾病复发的有价值的指标。
