간동맥색전술로 치료받은 간세포암종 환자의 예후예측인자로서 혈청 osteopontin의 의의
Prognostic value of serum osteopontin in hepatocellular carcinoma patients treated with transarterial chemoembolization
1
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
목적: 최근에 보고된 여러 연구들에 의하면, osteopontin의 과발현이 수술 후 재발하거나, 전이가 동반된 간세포암종에서 관찰되고 있다. 그러나 간세포암종 환자에서 간동맥색전술 후 예후평가인자로서 osteopontin의 의미는 아직까지 밝혀진 바가 없다. 따라서, 본 연구는 간세포암종 환자에서 간동맥색전술 전후 혈청 osteopontin 값의 변화를 중심으로 예후예측인자로서 혈청 osteopontin의 임상적 의의를 알아보고자 하였다. 대상과 방법: 조직검사로 진단된 총 46명의 간세포암종 환자가 본 연구에 포함되었으며, 간세포암종으로 진단된 후 간동맥색전술 전과 4주 후에 혈청 osteopontin을 ELISA법으로 측정하였다. 그 후 일반혈액검사, 생화학검사 및 전산화단층촬영검사를 정기적으로 시행하여 환자의 임상적 경과를 관찰하였으며, 이를 바탕으로 간동맥색전술 시행 전의 혈청 osteopontin 값 및 시술 후의 변화와 기저 임상양상, 치료반응, 누적생존율 간의 연관성을 분석하였다. 본 연구에서 혈청 osteopontin 치의 감소는 간동맥색전술 후 기저값에 비하여 10% 이상 감소한 것으로 정의하였고, 간동맥색전술에 대한 치료반응은 시술 후 4주 뒤에 시행한 전산화단층촬영에서 종양 괴사율이 50% 이상인 상태로 정의하였다. 결과: 대상 환자의 기저질환으로는 만성 B형간염이 우세하였고(33), 그 밖에 만성 C형간염(4), 비B형C형간염(9)으로 분류되었다. 기저 혈청 osteopontin 값이 높은 군은 상대적으로 큰 종양, 간문맥전이, 진행된 병기 등 종양 상태가 진행된 환자가 많았으며, 치료반응이 낮고(P=0.043), 누적생존율도 낮았다(P=0.036). 또한, 간동맥색전술 후 혈청 osteopontin이 감소한 군에서 그렇지 않은 군에 비해 치료반응을 보인 예가 많은 경향을 보였으며(P=0.055), 누적생존율이 유의하게 높았다(P<0.05). 그러나 다변량 분석에서는 혈청 osteopontin의 기저값과 시술 후의 변화는 생존율의 유의한 독립적 예측인자는 아니었다. 결론: 혈청 osteopontin 값은 간세포암종의 병기가 진행된 환자군에서 높으며, 간동맥색전술 시술 전 혈청 osteopontin 값이 낮거나 시술 후 감소하는 경우 치료반응이 좋고 생존율도 높다.
Abstract
Background/Aims: Osteopontin (OPN) is overexpressed in hepatocellular carcinoma (HCC) with postoperative recurrence or extrahepatic metastasis. However, its prognostic value in patients treated with transarterial chemoembolization (TACE) is unclear. We investigated the utility of serum OPN levels and changes therein as prognostic markers in HCC patients who have received TACE. Methods: Forty-six patients with HCC were enrolled. Serum OPN levels were measured before and 4 weeks after TACE. Serum biochemistry and computed tomography (CT) scans were analyzed. We evaluated baseline serum OPN levels and subsequent changes therein in relation to tumor responses and cumulative survival rates following TACE. A decreasing pattern was defined as a decrease after TACE of more than 10% relative to baseline levels. A “responder” was defined as a patient who exhibited a tumor necrosis rate of higher than 50% on the follow-up CT scan. Results: Higher initial serum OPN levels were associated with a large tumor, portal vein invasion, and an advanced tumor stage. Patients who had lower initial serum OPN levels and those who exhibited decreasing patterns after TACE tended to have more favorable tumor responses (P=0.043 and 0.055, respectively) and exhibited better cumulative survival rates (P=0.036 and 0.030, respectively). However, the initial serum OPN level and subsequent changes in serum OPN levels were not independent predictors for survival on multivariate analysis. Conclusions: Serum OPN levels were significantly higher in patients with advanced HCC. In addition, HCC patients with low pretreatment serum OPN levels and those for whom serum OPN declined following TACE exhibited better tumor responses and survived for longer.
참고문헌 (26)
- El-Serag HB, "Rising incidence of hepatocellular carcinoma in the United States", N Eng J Med, 340, pp.745~750 (1999)
- He J, "Major causes of death among men and women in China", N Eng J Med, 353, pp.1124~1134 (2005)
- Jemal A, "Cancer statistics, 2003", CA Cancer J Clin, 53, pp.5~26 (2003)
- Primary liver cancer in Japan, "Clinicopathologic features and surgical treatment", Liver Cancer Study Group of Japan. Ann Surg, 211, pp.277~287 (1990)
- Lee JK, "Recurrences of hepatocellular carcinoma following initial remission by transcatheter arterial chemoembolization", J Gastroenterol Hepatol, 17, pp.52~58 (2002)
- Nouso K, "Risk factors for local and recurrence of hepatocellular carcinomas after local ablation therapies", J Gastroenterol Hepatol, 23, pp.453~458 (2008)
- Collier J, "Screening for hepatocellular carcinoma", Hepatology, 27, pp.273~278 (1998)
- Weitz IC, "Des-gamma-carboxy (abnormal) prothrombin and hepatocellular carcinoma: a critical review", Hepatology, 18, pp.990~997 (1993)
- Midorikawa Y, "Glypican-3, overexpressed in hepatocellular carcinoma, modulates FGF2 and BMP-7 signaling", Int J Cancer, 103, pp.455~465 (2003)
- Sodek J, "Osteopontin", Crit Rev Oral Biol Med, 11, pp.279~303 (2000)
- Furger KA, "The functional and clinical roles of osteopontin in cancer and metastasis", Curr Mol Med, 1, pp.621~632 (2001)
- Shijubo N, "Vascular endothelial growth factor and osteopontin in tumor biology", Crit Rev Oncog, 11, pp.135~146 (2000)
- Ue T, "Co-expression of osteopontin and CD44v9 in gastric cancer", Int J Cancer 1998;79:127-132., 79, pp.127~132 (1998)
- Rudland PS, "Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer", Cancer Res, 62, pp.3417~3427 (2002)
- Carlinfante G, "Differential expression of osteopontin and bone sialoprotein in bone metastasis of breast and prostate carcinoma", Clin Exp Metastasis, 20, pp.437~444 (2003)
- Chambers AF, "Osteopontin expression in lung cancer", Lung Cancer, 15, pp.311~323 (1996)
- Agrawal D, "Osteopontin identified as lead marker of colon cancer progression, using pooled sample expression profiling", J Natl Cancer Inst, 94, pp.513~521 (2002)
- Gotoh M, "Overexpression of osteopontin in hepatocellular carcinoma", Pathol Int, 52, pp.19~24 (2002)
- Pan HW, "Overexpression of osteopontin is associated with intrahepatic metastasis, early recurrence, and poorer prognosis of surgically resected hepatocellular carcinoma", Cancer, 98, pp.119~127 (2003)
- Therasse P, "New guideline to evaluate the response to treatment in solid tumors. Europe Organization for Research and Treatment of Cancer, National Institute of the United States, National Cancer Institute of Canada", J Natl Cancer Inst, 92, pp.205~216 (2000)
- Zhang H, "The prognostic significance of preoperative plasma levels of osteopontin in patients with hepatocellular carcinoma", J Cancer Res Clin Oncol, 132, pp.709~717 (2006)
- Xie H, "Prognostic significance of osteopontin in hepatitis B virus-related hepatocellular carcinoma", Dig Liver Dis, 39, pp.167~172 (2007)
- Ye QH, "Predicting hepatitis B-virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning", Nat Med, 9, pp.416~423 (2003)
- Liaw L, "The adhesive and migratory effects of osteopontin are mediated via distinct cell surface integrins. Role of alpha v beta 3 in smooth muscle cell migration to osteopontin in vitro", J Clin Invest, 95, pp.713~724 (1995)
- Xuan JW, "Site-directed mutagenesis of the arginine-glycine-aspartic acid sequence in osteopontin destroys cell adhesion and migration functions", J Cell Biochem, 57, pp.680~690 (1995)
- Weber GF, "The metastasis gene osteopontin: a candidate target for cancer therapy", Biochem Biophys Acta, 1552, pp.61~85 (2001)