诊断学理论与实践 ›› 2026, Vol. 25 ›› Issue (03): 337-345.doi: 10.16150/j.1671-2870.2026.03.010
李劲哲1a,2, 林慧敏1a,2, 吴忻禹1a, 邓嵘1a, 刘鹏1a, 杨宇尘1b, 严福华1a,2(
)
收稿日期:2026-03-30
修回日期:2026-05-12
接受日期:2026-05-12
出版日期:2026-06-25
发布日期:2026-06-27
通讯作者:
严福华 E-mail:yfh11655@rjh.com.cn作者简介:作者贡献/Authors’ Contributions
李劲哲负责撰写文章(初写),林慧敏、吴忻禹、严福华负责修改文章,邓嵘、刘鹏、杨宇尘负责收集数据。
基金资助:
LI Jingzhe1a,2, LIN Huimin1a,2, WU Xinyu1a, DENG Rong1a, LIU Peng1a, YANG Yuchen1b, YAN Fuhua1a,2(
)
Received:2026-03-30
Revised:2026-05-12
Accepted:2026-05-12
Published:2026-06-25
Online:2026-06-27
摘要:
目的:探讨磁共振磷谱成像(31P magnetic resonance spectroscopic imaging, 31P MRSI)在肝细胞癌(hepatocellular carcinoma, HCC)患者首次肝动脉灌注化疗(hepatic arterial infusion chemotherapy, HAIC)疗效评估中的价值。方法:前瞻性连续收集2023年11月至2024年8月间上海交通大学医学院附属瑞金医院收治的计划接受HAIC的HCC(巴塞罗那临床分期C期)患者13例,均为男性,平均年龄(54±14)岁。所有患者在接受第1次HAIC前[平均(1±1) d]和后[平均(24±6) d],接受31P MRSI检查。在患者接受第6次HAIC[距首次HAIC中位151 d(四分位间距为123~179 d)后或在患者接受转化手术[距首次HAIC中位94 d(四分位间距为66~106 d)]后,根据修订后的实体瘤疗效评价标准(modified response evaluation criteria in solid tumor, mRECIST)或病理评估标准,将患者分为应答组(n=6)与无应答组(n=7)。分析HCC患者磷酸单酯(phosphomonoester, PME)/磷酸二酯(phosphodiester, PDE)比值及磷酸乙醇胺(phosphoethanolamine, PE)/PDE比值在首次HAIC后的变化及变化幅度(ΔPME/PDE和ΔPE/PDE),比较上述指标在首次HAIC前后改变的组间差异,采用受试者工作特征(receiver operating characteristic,ROC)曲线下面积评估上述指标预测HAIC疗效的价值。结果:应答组HAIC治疗前后PME/PDE比值、PE/PDE比值没有变化,无应答组显著升高。治疗前,无应答组PME/PDE比值(0.97比1.91,P=0.027)和PE/PDE比值(0.55比1.23,P=0.014)低于应答组。在无应答组中,治疗后的平均PME/PDE比值(3.04比0.97,P=0.006)和平均PE/PDE比值(2.03比0.55,P=0.014)均较治疗前显著升高;首次HAIC前后,ΔPME/PDE和ΔPE/PDE(1.69比0.40,P=0.029;1.80比0.47,P=0.032)显著大于应答组。HAIC前,PME/PDE比值<0.91、PE/PDE比值<0.74以及HAIC前后相应的ΔPME/PDE≥0.4、ΔPE/PDE≥2.2预测无应答的ROC曲线下面积分别为0.83、0.91、0.86和0.83。结论:对HAIC无应答的HCC患者,在首次HAIC后PME/PDE比值和PE/PDE比值升高。基线及首次HAIC后的PME/PDE比值和PE/PDE比值有望用于预测HAIC的疗效。
中图分类号:
李劲哲, 林慧敏, 吴忻禹, 邓嵘, 刘鹏, 杨宇尘, 严福华. 磁共振磷谱成像评估进展期肝细胞癌肝动脉灌注化疗疗效价值的前瞻性研究[J]. 诊断学理论与实践, 2026, 25(03): 337-345.
LI Jingzhe, LIN Huimin, WU Xinyu, DENG Rong, LIU Peng, YANG Yuchen, YAN Fuhua. Prospective study on value of 31P magnetic resonance spectroscopic imaging in evaluating efficacy of hepatic arterial infusion chemotherapy for advanced-stage hepatocellular carcinoma[J]. Journal of Diagnostics Concepts & Practice, 2026, 25(03): 337-345.
表1
SpectroView拟合参数
| Label | Chem shift (ppm) | Multiplet | J-coupling (Hz) | Guess width | Freq group | Width group |
|---|---|---|---|---|---|---|
| Inorganic phosphate | 4.77 | 1 | 0 | 0.01 | 1 | 3 |
| Glycerophosphocholine | 2.94 | 1 | 0 | 0.01 | 1 | 3 |
| Glycerophosphoethanolamine | 3.47 | 1 | 0 | 0.01 | 1 | 3 |
| PC | 6.21 | 1 | 0 | 0.01 | 1 | 2 |
| PCr | 0 | 1 | 0 | 0.01 | 1 | 1 |
| PE | 6.74 | 1 | 0 | 0.01 | 1 | 2 |
| α-ATP | -7.64 | 1 | 17 | 0.01 | 1 | 2 |
| β-ATP | -16.35 | 3 | 17 | 0.01 | 1 | 2 |
| γ-ATP | -2.59 | 2 | 17 | 0.01 | 1 | 2 |
表2
HCC患者HAIC治疗前后临床特征
| Characteristic | Before HAIC | After the first cycle of HAIC | P |
|---|---|---|---|
| Lesions diameter (mm) | 102.79±49.68 | 95.89±48.55 | 0.079 |
| Laboratory information | |||
| AFP (ng/mL) | 1 872.08 (78.83-31 716.00) | 1 456.59 (18.1-15 730.00) | 0.034 |
| PAB (mg/L) | 131.08±65.30 | 138.23±51.82 | 0.698 |
| ALB (g/L) | 35.54±4.39 | 34.15±5.34 | 0.293 |
| TP (g/L) | 66.46±5.29 | 69.54±4.59 | 0.128 |
| ALT (U/L) | 39.92±33.21 | 38.85±44.81 | 0.864 |
| AST (U/L) | 99.92±59.61 | 104.69±73.93 | 0.752 |
| INR | 1.13±0.11 | 1.12±0.09 | 0.872 |
| PT (s) | 13.00 (12.20-14.20) | 12.80 (12.70-13.70) | 0.839 |
| PLT (×109/L) | 188.69±58.39 | 191.08±130.94 | 0.940 |
表3
无应答组在HAIC前后的临床特征
| Characteristic | Before HAIC | After the first cycle of HAIC | P value |
|---|---|---|---|
| Lesions diameter (mm) | 102.89±44.08 | 98.44±44.84 | 0.556 |
| Laboratory information | |||
| AFP (ng/mL) | 57.08 (31.34-1 872.08) | 18.13 (5.89-1 394.84) | 0.125 |
| PAB (mg/L) | 156.80±27.53 | 127.40±40.62 | 0.197 |
| ALB (g/L) | 37.00±4.85 | 32.80±7.09 | 0.017 |
| TP (g/L) | 67.60±3.21 | 66.20±4.55 | 0.591 |
| ALT (U/L) | 58.40±48.73 | 60.60±69.44 | 0.897 |
| AST (U/L) | 81.60±49.92 | 95.00±66.32 | 0.496 |
| INR | 1.04±0.05 | 1.11±0.12 | 0.292 |
| PT (s) | 12.18±0.55 | 13.06±1.43 | 0.234 |
| PLT (×109/L) | 165.00±39.27 | 138.40±84.72 | 0.343 |
表4
应答组在HAIC前后的临床特征
| Characteristic | Before HAIC | After the first cycle of HAIC | P value |
|---|---|---|---|
| Lesions characteristic | |||
| Diameter (mm) | 107.55±53.93 | 93.91±49.16 | 0.015* |
| Laboratory information | |||
| AFP (ng/mL) | 12 868.61±17 248.64 | 12 566.95±21 136.97 | 0.961 |
| PAB (mg/L) | 125.50±86.88 | 146.67±70.12 | 0.523 |
| ALB (g/L) | 34.50±3.73 | 34.50±4.81 | 0.999 |
| TP (g/L) | 65.33±4.84 | 71.67±3.67 | 0.051 |
| ALT (U/L) | 25.83±6.71 | 25.83±12.09 | 0.999 |
| AST (U/L) | 109.00±76.98 | 109.67±86.48 | 0.980 |
| INR | 1.18±0.10 | 1.14±0.07 | 0.343 |
| PT (s) | 13.88±1.11 | 12.98±0.73 | 0.130 |
| PLT (×109/L) | 187.33±47.80 | 194.67±150.36 | 0.882 |
| [1] | 王嘉琛, 何思怡, 曹梦迪, 等. 1990—2021年中国人群5种常见消化系统恶性肿瘤疾病负担变化趋势分析[J]. 中华消化外科杂志, 2025, 24(2):213-222. |
| WANG J C, HE S Y, CAO M D, et al. Analysis of the change trend in the burden of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021[J]. Chin J Dig Surg, 2025, 24(2):213-222. | |
| [2] |
LYU N, KONG Y, MU L, et al. Hepatic arterial infusion of oxaliplatin plus fluorouracil/leucovorin vs. sorafenib for advanced hepatocellular carcinoma[J]. J Hepatol, 2018, 69(1):60-69.
doi: 10.1016/j.jhep.2018.02.008 URL |
| [3] | LI Q J, HE M K, CHEN H W, et al. Hepatic arterial infusion of oxaliplatin, fluorouracil, and leucovorin versus transarterial chemoembolization for large hepatocellular carcinoma: A randomized phase Ⅲ trial[J]. J Clin Oncol, 2022, 40(2):150-160. |
| [4] |
EISENHAUER E A, THERASSE P, BOGAERTS J, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)[J]. Eur J Cancer, 2009, 45(2):228-247.
doi: 10.1016/j.ejca.2008.10.026 pmid: 19097774 |
| [5] |
DENG M, ZHONG C, LI D, et al. Hepatic arterial infusion chemotherapy-based conversion hepatectomy in responders versus nonresponders with hepatocellular carcinoma: A multicenter cohort study[J]. Int J Surg, 2025, 111(1):135-145.
doi: 10.1097/JS9.0000000000002043 URL |
| [6] |
ZHAO M, GUO Z, ZOU Y H, et al. Arterial chemotherapy for hepatocellular carcinoma in China: Consensus recommendations[J]. Hepatol Int, 2024, 18(1):4-31.
doi: 10.1007/s12072-023-10599-6 |
| [7] |
VAN DEN WILDENBERG L, RUNDERKAMP B A, SEELEN L W F, et al. Measurement of metabolite levels and treatment-induced changes in hepatic metastases of gastro-esophageal cancer using 7-T phosphorus magnetic resonance spectroscopic imaging[J]. NMR Biomed, 2024, 37(9):e5155.
doi: 10.1002/nbm.v37.9 URL |
| [8] |
BELL J D, BHAKOO K K. Metabolic changes underlying 31P MR spectral alterations in human hepatic tumours[J]. NMR Biomed, 1998, 11(7):354-359.
doi: 10.1002/(ISSN)1099-1492 URL |
| [9] | SEELEN L W F, VAN DEN WILDENBERG L, VAN DER KEMP W J M, et al. Prospective of 31P MR spectroscopy in hepatopancreatobiliary cancer: A systematic review of the literature[J]. Magnetic Resonance Imaging, 2023, 57(4):1144-1155. |
| [10] |
MEYERHOFF D J, KARCZMAR G S, VALONE F, et al. Hepatic cancers and their response to chemoembolization therapy: Quantitative image-guided 31P magnetic resonance spectroscopy[J]. Investig Radiol, 1992, 27(6):456-464.
doi: 10.1097/00004424-199206000-00011 URL |
| [11] |
SCHILLING A, GEWIESE B, BERGER G, et al. Liver tumors: Follow-up with P-31 MR spectroscopy after local chemotherapy and chemoembolization[J]. Radiology, 1992, 182(3):887-890.
pmid: 1311119 |
| [12] |
MARRERO J A, KULIK L M, SIRLIN C B, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American association for the study of liver diseases[J]. Hepatology, 2018, 68(2):723-750.
doi: 10.1002/hep.29913 pmid: 29624699 |
| [13] |
REIG M, FORNER A, RIMOLA J, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update[J]. J Hepatol, 2022, 76(3):681-693.
doi: 10.1016/j.jhep.2021.11.018 URL |
| [14] |
JONUSCHEIT M, WIERICHS S, ROTHE M, et al. Reproducibility of absolute quantification of adenosine triphosphate and inorganic phosphate in the liver with localized 31P-magnetic resonance spectroscopy at 3-T using differe-nt coils[J]. NMR Biomed, 2024, 37(8):e5120.
doi: 10.1002/nbm.v37.8 URL |
| [15] |
LIN A, ANDRONESI O, BOGNER W, et al. Minimum reporting standards for in vivo magnetic resonance spectroscopy (MRSinMRS): Experts' consensus recommendations[J]. NMR Biomed, 2021, 34(5):e4484.
doi: 10.1002/nbm.4484 pmid: 33559967 |
| [16] |
SEVASTIANOVA K, HAKKARAINEN A, KOTRONEN A, et al. Nonalcoholic fatty liver disease: Detection of elevated nicotinamide adenine dinucleotide phosphate with in vivo 3.0-T31P MR spectroscopy with proton decoupling[J]. Radiology, 2010, 256(2):466-473.
doi: 10.1148/radiol.10091351 URL |
| [17] |
VAN DEN WILDENBERG L, GURSAN A, SEELEN L W F, et al. In vivo phosphorus magnetic resonance spectroscopic imaging of the whole human liver at 7T using a phosphorus whole-body transmit coil and 16-channel receive array: Repeatability and effects of principal component analysis-based denoising[J]. NMR Biomed, 2023, 36(5):e4877.
doi: 10.1002/nbm.v36.5 URL |
| [18] |
MARJAŃSKA M, DEELCHAND D K, KREIS R. Results and interpretation of a fitting challenge for MR spectroscopy set up by the MRS study group of ISMRM[J]. Magn Reson Med, 2022, 87(1):11-32.
doi: 10.1002/mrm.v87.1 URL |
| [19] |
ZHANG Y, SHEN J. Smoothness of in vivo spectral baseline determined by mean-square error: Smoothness of in Vivo Spectral Baseline[J]. Magn Reson Med, 2014, 72(4):913-922.
doi: 10.1002/mrm.25013 pmid: 24259436 |
| [20] | YANG C, CHEN Y, SHENG L, et al. Prediction of pathologic response in unresectable hepatocellular carcinoma after downstaging with locoregional and systemic combination therapy[J]. J Hepatocell Carcinoma, 2025,12:43-58. |
| [21] | LENCIONI R, LLOVET J. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma[J]. Semin Liver Dis 2010, 30(1):52-60. |
| [22] |
WANG Z, FAN J, ZHOU S, et al. Perioperative camrelizumab plus rivoceranib versus surgery alone in patients with resectable hepatocellular carcinoma at intermediate or high risk of recurrence (CARES-009): A randomised phase 2/3 trial[J]. Lancet, 2025, 406(10515):2089-2099.
doi: 10.1016/S0140-6736(25)01720-9 URL |
| [23] |
NAKAGAWA S. A farewell to Bonferroni: The problems of low statistical power and publication bias[J]. Behav Ecol, 2004, 15(6):1044-1045.
doi: 10.1093/beheco/arh107 URL |
| [24] |
LOHITESH K, CHOWDHURY R, MUKHERJEE S. Resistance a major hindrance to chemotherapy in hepatocellular carcinoma: An insight[J]. Cancer Cell Int, 2018, 18(1):44.
doi: 10.1186/s12935-018-0538-7 |
| [25] |
YIN X, TANG B, LI J H, et al. ID1 promotes hepatocellular carcinoma proliferation and confers chemoresistance to oxaliplatin by activating pentose phosphate pathway[J]. J Exp Clin Cancer Res, 2017, 36(1):166.
doi: 10.1186/s13046-017-0637-7 pmid: 29169374 |
| [26] |
WEN S Y, LIU Y T, WEI B Y, et al. PDCD6 Promotes hepatocellular carcinoma cell proliferation and metastasis through the AKT/GSK3β/β-catenin pathway[J]. Biomed Environ Sci, 2023, 36(3):241-252.
doi: 10.3967/bes2023.027 pmid: 37005078 |
| [27] | GAO Z X, ZHANG Z S, QIN J, et al. Aucubin enhances the antitumor activity of cisplatin through the inhibition of PD-L1 expression in hepatocellular carcinoma[J]. Phytomedicine, 2023,112:154715. |
| [28] | LEI Y, CAI S, ZHANG J K, et al. The role and mechanism of fatty acid oxidation in cancer drug resistance[J]. Cell Death Discov, 2025,11:277. |
| [29] |
ZHU Y, YAN W, TONG L, et al. Metabolic reprogramming: A crucial contributor to anticancer drug resistance[J]. MedComm, 2025, 6(9):e70358.
doi: 10.1002/mco2.70358 |
| [30] | PIATRIKOVA V, KOCIANOVA E, SKVARKOVA L, et al. Fuelling resistance: Lipid metabolic rewiring in cancer response to chemotherapy and radiotherapy[J]. Biomed Pharmacother, 2025,193:118715. |
| [31] | 中国抗癌协会肝癌专业委员会转化治疗协作组. 中国肝癌转化治疗中心建设参考标准(2024版)[J]. 中华消化外科杂志, 2025, 24(1):41-47. |
| Alliance of Liver Cancer Conversion Therapy, Committee of Liver Cancer, China Anti‐Cancer Association. Chinese reference standard of conversion therapy center construction for liver cancer (2024 edition)[J]. Chin J Dig Surg, 2025, 24(1):41-47. | |
| [32] | 中国抗癌协会肝癌专业委员会病理学组, 中国抗癌协会肿瘤病理专业委员会肝癌学组. 肝细胞癌新辅助及转化治疗后疗效病理学评估专家共识(2025版)[J]. 中华消化外科杂志, 2025, 24(9):1117-1123. |
| Pathology Group of Liver Cancer Professional Committee of the Chinese Anti-Cancer Association, Liver Cancer Group of Oncology Pathology Professional Committee of the Chinese Anti-Cancer Association. Expert consensus on pathological evaluation of efficacy after neoadjuvant and conversion therapy for hepatocellular carcinoma (2025 edition)[J]. Chin J Dig Surg, 2025, 24(8):1117-1123. | |
| [33] |
YUAN Z, YE X D, DONG S, et al. Evaluation of early imaging response after chemoembolization of hepatocellular carcinoma by phosphorus-31 magnetic resonance spectroscopy: Initial experience[J]. J Vasc Interv Radiol, 2011, 22(8):1166-1173.
doi: 10.1016/j.jvir.2011.04.010 URL |
| [34] |
GIBELLINI F, SMITH T K. The Kennedy pathway: De novo synthesis of phosphatidylethanolamine and phosphatidylcholine[J]. IUBMB Life, 2010, 62(6):414-428.
doi: 10.1002/iub.v62:6 URL |
| [35] |
PULICA R, AQUIB A, VARSANYI C, et al. Dys-regulated phosphatidylserine externalization as a cell intrinsic immune escape mechanism in cancer[J]. Cell Commun Signal, 2025, 23(1):131.
doi: 10.1186/s12964-025-02090-6 pmid: 40069722 |
| [36] | PRETA G. New insights into targeting membrane lipids for cancer therapy[J]. Front Cell Dev Biol, 2020,8:571237. |
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