|
|
肝细胞癌根治性切除术后无复发生存时间和总生存的影响因素分析
|
Abstract:
目的：本研究的目的是调查影响接受根治性切除术的肝细胞癌(HCC)患者无病生存期(RFS)和总生存期(OS)的重要血清因子。患者和方法：从2011年到2018年，我们中心招募了187名接受肝癌根治性手术的患者。使用Kaplan-Meier方法生成生存曲线，并使用对数秩检验进行比较。使用单变量和多变量Cox比例风险模型评估RFS和OS的预后因素。结果：单因素和多变量分析表明，前白蛋白(PAB) (p = 0.016)和GGT (p = 0.007)与RFS独立相关，GGT (p = 0.039)、GGT/PAB (p = 0.038)和GGT/AST (p = 0.035)与OS独立相关。结论：根治性手术后原发性肝细胞癌的预后受多种因素影响。血清GGT、PAB、GGT/PAB和GGT/AST水平可作为评估术后患者预后的方便且经济的方法。
Objective: The aim of the current study was to investigate the significant serum factors that influence recurrence-free survival (RFS) and overall survival (OS) in hepatocellular carcinoma (HCC) patients who receive curative resection. Patients and Methods: From 2011 to 2018, 187 patients who underwent radical surgery for HCC in our center were recruited. Survival curves were generated using the Kaplan-Meier method and compared using a log-rank test. The prognostic factors of RFS and OS were assessed using univariate and multivariable Cox proportional hazards models. Results: The univariate and multivariable analyses demonstrated that prealbumin (PAB) (p = 0.016) and GGT (p = 0.007) were independently associated with RFS, GGT (p = 0.039), GGT/PAB (p = 0.038) and GGT/AST (p = 0.035) were independently associated with OS. Conclusion: The prognosis of primary HCC after curative surgery can be influenced by many factors. Serum levels of GGT, PAB, GGT/PAB and GGT/AST might be used as convenient and economical methods for evaluating the prognosis of patients after surgery.
| [1] | Llovet, J.M., Kelley, R.K., Villanueva, A., et al. (2021) Hepatocellular Carcinoma. Nature Reviews Disease Primers, 7, Article No. 6. https://doi.org/10.1038/s41572-020-00240-3 |
| [2] | Ringelhan, M., Pfister, D., O’Connor, T., Pikarsky, E. and Heikenwalder, M. (2018) The Immunology of Hepatocellular Carcinoma. Nature Immunology, 19, 222-232. https://doi.org/10.1038/s41590-018-0044-z |
| [3] | Abou-Alfa, G.K., Meyer, T., Cheng, A.L., El-Khoueiry, A.B., Rimassa, L., Ryoo, B.Y., Cicin, I., Merle, P., Chen, Y., Park, J.W., et al. (2018) Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma. The New England Journal of Medicine, 379, 54-63. https://doi.org/10.1056/NEJMoa1717002 |
| [4] | Llovet, J.M., Montal, R. and Villanueva, A. (2019) Randomized Trials and Endpoints in Advanced HCC: Role of PFS as a Surrogate of Survival. Journal of Hepatology, 70, 1262-1277. https://doi.org/10.1016/j.jhep.2019.01.028 |
| [5] | Xia, C., Dong, X., Li, H., Cao, M., Sun, D., He, S., Yang, F., Yan, X., Zhang, S., Li, N. and Chen, W. (2022) Cancer Statistics in China and United States, 2022: Profiles, Trends, and Determinants. Chinese Medical Journal, 135, 584-590. https://doi.org/10.1097/CM9.0000000000002108 |
| [6] | Lin, M.V., King, L.Y. and Chung, R.T. (2015) Hepatitis C Virus-Associated Cancer. Annual Review of Pathology, 10, 345-370. https://doi.org/10.1146/annurev-pathol-012414-040323 |
| [7] | Omata, M.,Cheng, A.L., Kokudo, N., Kudo, M., Lee, J.M., Jia, J., Tateishi, R., Han, K.H., Chawla, Y.K., Shiina, S., et al. (2017) Asia-Pacific Clinical Practice Guidelines on the Management of Hepatocellular Carcinoma: A 2017 Update. Hepatology International, 11, 317-370. https://doi.org/10.1007/s12072-017-9799-9 |
| [8] | Thayer, D., Noda, C., Charalel, R., Mills, A., Chang, R., Tao, Y. and Akinwande, O. (2018) Survival Comparison of Hepatocellular Carcinoma Patients Treated with Radioembolization versus Nonoperative/Interventional Treatment. Journal of Comparative Effectiveness Research, 7, 343-356. https://doi.org/10.2217/cer-2017-0064 |
| [9] | Vogel, A., Cervantes, A., Chau, I., Daniele, B., Llovet, J.M., Meyer, T., Nault, J.C., Neumann, U., Ricke, J., Sangro, B., et al. (2019) Hepatocellular Carcinoma: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up. Annals of Oncology, 30, 871-873. https://doi.org/10.1093/annonc/mdy510 |
| [10] | Liang, Y.J., Teng, W., Chen, C.L., Sun, C.P., Teng, R.D., Huang, Y.H., Liang, K.H., Chen, Y.W., Lin, C.C., Su, C.W., et al. (2021) Clinical Implications of HBV PreS/S Mutations and the Effects of PreS2 Deletion on Mitochondria, Liver Fibrosis, and Cancer Development. Hepatology, 74, 641-655. https://doi.org/10.1002/hep.31789 |
| [11] | Wang, X., Mao, M., He, Z., Zhang, L., Li, H., Lin, J., He, Y., Dai, S., Hu, W. and Liu, W. (2019) Development and Validation of a Prognostic Nomogram in AFP-Negative Hepatocellular Carcinoma. International Journal of Biological Sciences, 15, 221-228. https://doi.org/10.7150/ijbs.28720 |
| [12] | Wu, X., Zhou, J., Sun, Y., Ding, H., Chen, G., Xie, W., Piao, H., Xu, X., Jiang, W., Ma, H., et al. (2021) Prediction of Liver-Related Events in Patients with Compensated HBV-Induced Cirrhosis Receiving Antiviral Therapy. Hepatology International, 15, 82-92. https://doi.org/10.1007/s12072-020-10114-1 |
| [13] | Li, J.D., Xu, X.F., Han, J., Wu, H., Xing, H., Li, C., Yu, J.J., Zhou, Y.H., Gu, W.M., Wang, H., et al. (2019) Preoperative Prealbumin Level as an Independent Predictor of Long-Term Prognosis after Liver Resection for Hepatocellular Carcinoma: A Multi-Institutional Study. Hepato-Pancreato-Biliary, 21, 157-166. https://doi.org/10.1016/j.hpb.2018.06.1803 |
| [14] | Ozcelik, F. (2021) Prognostic Value of Gamma-Glutamyl Transpeptidase in Liver Cirrhosis and Hepatocellular Cancer Regardless of other Parameters. Clinics and Research in Hepatology and Gastroenterology, 45, Article 101708. https://doi.org/10.1016/j.clinre.2021.101708 |
| [15] | Cong, W.M., Bu, H., Chen, J., Dong, H., Zhu, Y.Y., Feng, L.H. and Chen, J. (2016) Practice Guidelines for the Pathological Diagnosis of Primary Liver Cancer: 2015 Update. World Journal of Gastroenterology, 22, 9279-9287. https://doi.org/10.3748/wjg.v22.i42.9279 |
| [16] | Kabbach, G., Assi, H.A., Bolotin, G., Schuster, M., Lee, H.J. and Tadros, M. (2015) Hepatobiliary Tumors: Update on Diagnosis and Management. Journal of Clinical and Translational Hepatology, 3, 169-181. https://doi.org/10.14218/JCTH.2015.00012 |
| [17] | Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A. and Jemal, A. (2018) Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 68, 394-424. https://doi.org/10.3322/caac.21492 |
| [18] | Chan, A., Zhang, W.Y., Chok, K., Dai, J., Ji, R., Kwan, C., Man, N., Poon, R. and Lo, C.M. (2021) ALPPS versus Portal Vein Embolization for Hepatitis-Related Hepatocellular Carcinoma: A Changing Paradigm in Modulation of Future Liver Remnant before Major Hepatectomy. Annals of Surgery, 273, 957-965. https://doi.org/10.1097/SLA.0000000000003433 |
| [19] | Hanazaki, K., Kajikawa, S., Shimozawa, N., Mihara, M., Shimada, K., Hiraguri, M., Koide, N., Adachi, W. and Amano, J. (2000) Survival and Recurrence after Hepatic Resection of 386 Consecutive Patients with Hepatocellular Carcinoma. Journal of the American College of Surgeons, 191, 381-388. https://doi.org/10.1016/S1072-7515(00)00700-6 |
| [20] | Liu, L., Wang, W., Zhang, Y., Long, J., Zhang, Z., Li, Q., Chen, B., Li, S., Hua, Y., Shen, S. and Peng, B. (2018) Declined Preoperative Aspartate Aminotransferase to Neutrophil Ratio Index Predicts Poor Prognosis in Patients with Intrahepatic Cholangiocarcinoma after Hepatectomy. Cancer Research and Treatment, 50, 538-550. https://doi.org/10.4143/crt.2017.106 |
| [21] | Anwanwan, D., Singh, S.K., Singh, S., Saikam, V. and Singh, R. (2020) Challenges in Liver Cancer and Possible Treatment Approaches. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 1873, Article 188314. https://doi.org/10.1016/j.bbcan.2019.188314 |
| [22] | Zhou, H. and Song, T. (2021) Conversion Therapy and Maintenance Therapy for Primary Hepatocellular Carcinoma. BioScience Trends, 15, 155-160. https://doi.org/10.5582/bst.2021.01091 |
| [23] | Xiao, B., Li, D., Xu, H., Zhou, X., Xu, X., Qian, Y., Yu, F., Hu, H., Zhou, Z., Liu, X., et al. (2021) An MRI-Trackable Therapeutic Nanovaccine Preventing Cancer Liver Metastasis. Biomaterials, 274, Article 120893. https://doi.org/10.1016/j.biomaterials.2021.120893 |
| [24] | Ayuso, C., Rimola, J., Vilana, R., Burrel, M., Darnell, A., García-Criado, á., Bianchi, L., Belmonte, E., Caparroz, C., Barrufet, M., et al. (2018) Diagnosis and Staging of Hepatocellular Carcinoma (HCC): Current Guidelines. European Journal of Radiology, 101, 72-81. https://doi.org/10.1016/j.ejrad.2018.01.025 |
| [25] | Pi？ero, F., Dirchwolf, M. and Pess？a, M.G. (2020) Biomarkers in Hepatocellular Carcinoma: Diagnosis, Prognosis and Treatment Response Assessment. Cells, 9, Article 1370. https://doi.org/10.3390/cells9061370 |
| [26] | Beck, F.K. and Rosenthal, T.C. (2002) Prealbumin: A Marker for Nutritional Evaluation. American Family Physician, 65, 1575-1578. |
| [27] | Meng, J., Zhong, J., Zhang, H., Zhong, W., Huang, Z., Jin, Y. and Xu, J. (2014) Pre-, Peri-, and Postoperative Oral Administration of Branched-Chain Amino Acids for Primary Liver Cancer Patients for Hepatic Resection: A Systematic Review. Nutrition and Cancer, 66, 517-522. https://doi.org/10.1080/01635581.2013.780628 |
| [28] | Alifano, M., Mansuet-Lupo, A., Lococo, F., Roche, N., Bobbio, A., Canny, E., Schussler, O., Dermine, H., Régnard, J. F., Burroni, B., et al. (2014) Systemic Inflammation, Nutritional Status and Tumor Immune Microenvironment Determine Outcome of Resected Non-Small Cell Lung Cancer. PLOS ONE, 9, e106914. https://doi.org/10.1371/journal.pone.0106914 |
| [29] | Rymarz, A., Bartoszewicz, Z., Szamotulska, K. and Niemczyk, S. (2016) The Associations between Body Cell Mass and Nutritional and Inflammatory Markers in Patients with Chronic Kidney Disease and in Subjects without Kidney Disease. Journal of Renal Nutrition, 26, 87-92. https://doi.org/10.1053/j.jrn.2015.09.005 |
| [30] | Saito, M., Seo, Y., Yano, Y., Miki, A., Yoshida, M. and Azuma, T. (2012) Short-Term Reductions in Non-Protein Respiratory Quotient and Prealbumin Can be Associated with the Long-Term Deterioration of Liver Function after Transcatheter Arterial Chemoembolization in Patients with Hepatocellular Carcinoma. Journal of Gastroenterology, 47, 704-714. https://doi.org/10.1007/s00535-012-0535-x |
| [31] | Liu, F., Cai, L.Y., Zhong, L., Chen, C., Xu, F., Zhao, Z.X. and Chen, X.M. (2010) Model for End-Stage Liver Disease Combined with Serum Prealbumin to Predict the Prognosis of Patients with Decompensated Liver Cirrhosis. Journal of Digestive Diseases, 11, 352-357. https://doi.org/10.1111/j.1751-2980.2010.00465.x |
| [32] | Shirai, Y., Okugawa, Y., Hishida, A., Ogawa, A., Okamoto, K., Shintani, M., Morimoto, Y., Nishikawa, R., Yokoe, T., Tanaka, K., et al. (2017) Fish Oil-Enriched Nutrition Combined with Systemic Chemotherapy for Gastrointestinal Cancer Patients with Cancer Cachexia. Scientific Reports, 7, Article No. 4826. https://doi.org/10.1038/s41598-017-05278-0 |
| [33] | Tahan, V., Canbakan, B., Balci, H., Dane, F., Akin, H., Can, G., Hatemi, I., Olgac, V., Sonsuz, A., Ozbay, G., et al. (2008) Serum Gamma-Glutamyltranspeptidase Distinguishes Non-Alcoholic Fatty Liver Disease at High Risk. Hepatogastroenterology, 55, 1433-1438. |
| [34] | Hofbauer, S.L., Stangl, K.I., de Martino, M., Lucca, I., Haitel, A., Shariat, S.F. and Klatte, T. (2014) Pretherapeutic Gamma-Glutamyltransferase is an Independent Prognostic Factor for Patients with Renal Cell Carcinoma. British Journal of Cancer, 111, 1526-1531. https://doi.org/10.1038/bjc.2014.450 |
| [35] | Seebacher, V., Polterauer, S., Grimm, C., Rahhal, J., Hofstetter, G., Bauer, E.M., Husslein, H., Leipold, H., Marth, C., Reinthaller, A. and Concin, N. (2012) Prognostic Significance of Gamma-Glutamyltransferase in Patients with Endometrial Cancer: A Multi-Centre Trial. British Journal of Cancer, 106, 1551-1555. https://doi.org/10.1038/bjc.2012.16 |
| [36] | Yang, F., Zhang, S., Yang, H., Luo, K., Wen, J., Hu, Y., Hu, R., Huang, Q., Chen, J. and Fu, J. (2015) Prognostic Significance of Gamma-Glutamyltransferase in Patients with Resectable Esophageal Squamous Cell Carcinoma. Diseases of the Esophagus, 28, 496-504. https://doi.org/10.1111/dote.12227 |
| [37] | Kudo, M., Kawamura, Y., Hasegawa, K., Tateishi, R., Kariyama, K., Shiina, S., Toyoda, H., Imai, Y., Hiraoka, A., Ikeda, M., et al. (2021) Management of Hepatocellular Carcinoma in Japan: JSH Consensus Statements and Recommendations 2021 Update. Liver Cancer, 10, 181-223. https://doi.org/10.1159/000514174 |
| [38] | Zhang, L.X., Lv, Y., Xu, A.M. and Wang, H.Z. (2019) The Prognostic Significance of Serum Gamma-Glutamyltransferase Levels and AST/ALT in Primary Hepatic Carcinoma. BMC Cancer, 19, Article No. 841. https://doi.org/10.1186/s12885-019-6011-8 |
| [39] | Kunutsor, S.K., Apekey, T.A., Van Hemelrijck, M., Calori, G. and Perseghin, G. (2015) Gamma Glutamyltransferase, Alanine Aminotransferase and Risk of Cancer: Systematic Review and Meta-Analysis. International Journal of Cancer, 136, 1162-1170. https://doi.org/10.1002/ijc.29084 |
| [40] | Pompella, A., De Tata, V., Paolicchi, A. and Zunino, F. (2006) Expression of Gamma-Glutamyltransferase in Cancer Cells and Its Significance in Drug Resistance. Biochemical Pharmacology, 71, 231-238. https://doi.org/10.1016/j.bcp.2005.10.005 |
| [41] | Liu, X., Hou, Y., Wang, X., Yu, L., Wang, X., Jiang, L. and Yang, Z. (2020) Machine Learning-Based Development and Validation of a Scoring System for Progression-Free Survival in Liver Cancer. Hepatology International, 14, 567-576. https://doi.org/10.1007/s12072-020-10046-w |
| [42] | Russell, D.W. (2003) The Enzymes, Regulation, and Genetics of Bile Acid Synthesis. Annual Review of Biochemistry, 72, 137-174. https://doi.org/10.1146/annurev.biochem.72.121801.161712 |
| [43] | He, C., Peng, W., Li, C. and Wen, T.F. (2017) Postoperative Aspartate Aminotransferase to Lymphocyte Ratio Index Change is an Independent Predictor of Survival in Patients with Small Hepatocellular Carcinoma. Medicine (Baltimore), 96, e8540. https://doi.org/10.1097/MD.0000000000008540 |
| [44] | Giannini, E.G., Testa, R. and Savarino, V. (2005) Liver Enzyme Alteration: A Guide for Clinicians. Canadian Medical Association Journal, 172, 367-379. https://doi.org/10.1503/cmaj.1040752 |
