|
|
血清肿瘤标志物联合胆汁酸检测在胃癌诊断中的价值
|
Abstract:
目的：探讨血清肿瘤标志物(CEA、CA19-9、CA72-4)及胆汁酸(TBA)在胃癌诊断中的价值。方法：收集842例临床资料完整的胃癌患者的数据，采用秩和检验、受试者工作特征曲线分析CEA、CA19-9、CA72-4与TBA单独及联合检测在胃癌诊断中的价值。结果：胃癌组血清CEA、CA72-4、TBA水平明显高于健康对照组(Z = ？7.013~？3.387, P < 0.05)，胃癌组与对照组在CEA、CA19-9、CA72-4、TBA不同升高水平间有差异(P < 0.01)，且在升高小于等于1倍时，对照组胃癌患者占比均明显高于胃癌组。CEA升高大于4倍，CA19-9升高1~2倍、2~4倍、大于4倍，CA72-4升高1~2倍、2~4倍、大于4倍，TBA升高1~2倍、2~4倍时，胃癌组胃癌患者占比明显高于对照组。胃癌组不同分化程度血清CEA、CA19-9、CA72-4水平及升高程度均无统计学意义。有淋巴结转移组血清CEA、CA19-9、CA72-4、TBA水平明显高于无淋巴结转移组(Z = ？4.897~？1.826, P < 0.01)，有淋巴结转移的患者比例在不同升高水平的血清CEA、CA19-9中均明显高于无淋巴结转移的患者比例(P < 0.01)；胃癌有、无淋巴结转移在不同升高水平的血清CA72-4、TBA中均未见统计学意义(P > 0.05)。血清CEA、CA19-9、CA72-4、TBA联合检测的灵敏度高于单独检测，且四项指标联合检测灵敏度最高。ROC曲线中，CEA、CA72-4、TBA联合检测曲线下面积(AUC)最大为0.616。结论：血清CEA、CA19-9、CA72-4、TBA对胃癌的诊断价值不高，仅当其升高大于4倍时意义较大。只有当血清CEA、CA19-9水平升高大于4倍时，对胃癌是否有淋巴结转移预测价值较大。
Objective: To investigate the value of serum tumor markers (CEA, CA19-9, CA72-4) and bile acid (TBA) in the diagnosis of gastric cancer. Methods: The data of 842 gastric cancer patients with com-plete clinical data were collected, and the value of single and combined detection of CEA, CA19-9, CA72-4 and TBA in the diagnosis of gastric cancer was analyzed by Kruskal-Wallis test and receiver operating characteristic curve. Results: The levels of serum CEA, CA72-4 and TBA in gastric cancer group were significantly higher than those in healthy control group (Z = ？7.013~？3.387, P < 0.05). There were differences in the levels of CEA, CA19-9, CA72-4, and TBA between the gastric cancer group and the control group (P < 0.01), and when the increase was less than or equal to 1 times, the proportion of gastric cancer patients in the control group was significantly higher than that in the gastric cancer group. The proportion of patients with gastric cancer in the gastric cancer group was significantly higher than that in the control group when CEA increased by more than 4 times, CA19-9 increased by 2 times, 2 times, more than 4 times, CA72-4 increased by 2 times, 2 times, more than 4 times, and TBA increased by 1 times, 2 times, 4 times. There was no statistical signifi-cance in the levels of CEA, CA19-9, CA72-4 and TBA in different degrees of differentiation in gastric cancer group. The serum levels of CEA, CA19-9, CA72-4 and TBA in patients with lymph node me-tastasis were significantly higher than those without lymph node metastasis (Z = ？4.897~？1.826, P < 0.01). The proportion of patients with lymph node metastasis was significantly higher than that of patients without lymph node metastasis (P < 0.01). There was no significant difference between gastric cancer with
| [1] | Sung, H., Ferlay, J., Siegel, R.L., et al. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71, 209-249.
https://doi.org/10.3322/caac.21660 |
| [2] | 郑荣寿, 孙可欣, 张思维, 等. 2015年中国恶性肿瘤流行情况分析[J]. 中华肿瘤杂志, 2019, 41(1): 19-28. |
| [3] | Bray, F., Ferlay, J., Soerjomataram, I., et al. (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 |
| [4] | 徐采朴. 应重视早期胃癌的内镜诊断[J]. 世界华人消化杂志, 2002, 10(4): 373-375. |
| [5] | Yao, Y., Ding, Y., Bai, Y., et al. (2020) Identification of Serum Circulating MicroRNAs as Novel Diagnostic Biomarkers of Gastric Cancer. Frontiers in Genetics, 11, Article 591515. https://doi.org/10.3389/fgene.2020.591515 |
| [6] | Zheng, T.-H., Zhao, J.-L. and Guleng, B. (2015) Advances in Molecular Biomarkers for Gastric Cancer. Critical Reviews in Eukaryotic Gene Expression, 25, 299-305. https://doi.org/10.1615/CritRevEukaryotGeneExpr.2015014360 |
| [7] | Matsuoka, T. and Yashiro, M. (2018) Bi-omarkers of Gastric Cancer: Current Topics and Future Perspective. World Journal of Gastroenterology, 24, 2818-2832. https://doi.org/10.3748/wjg.v24.i26.2818 |
| [8] | Shimada, H., Noie, T., Ohashi, M., Oba, K. and Takahashi, Y. (2014) Clinical Significance of Serum Tumor Markers for Gastric Cancer: A Systematic Review of Literature by the Task Force of the Japanese Gastric Cancer Association. Gastric Cancer, 17, 26-33. https://doi.org/10.1007/s10120-013-0259-5 |
| [9] | Guo, L., Wang, Q., Chen, K., Liu, H.-P. and Chen, X. (2021) Prognostic Value of Combination of Inflammatory and Tumor Markers in Resectable Gastric Cancer. Journal of Gastro-intestinal Surgery, 25, 2470-2483.
https://doi.org/10.1007/s11605-021-04944-z |
| [10] | Bernstein, H., Bernstein, C., Payne, C.M., Dvorakova, K. and Garewal, H. (2005) Bile Acids as Carcinogens in Human Gastrointestinal Cancers. Mutation Research, 589, 47-65. https://doi.org/10.1016/j.mrrev.2004.08.001 |
| [11] | Kondo, K. (2002) Duodenogastric Reflux and Gastric Stump Carcinoma. Gastric Cancer, 5, 16-22.
https://doi.org/10.1007/s101200200002 |
| [12] | Komichi, D., Tazuma, S., Nishioka, T., Hyogo, H. and Chayama, K. (2005) Glycochenodeoxycholate Plays a Carcinogenic Role in Immortalized Mouse Cholangiocytes via Oxidative DNA Damage. Free Radical Biology & Medicine, 39, 1418-1427. https://doi.org/10.1016/j.freeradbiomed.2005.07.005 |
| [13] | Tatsugami, M., Ito, M., Tanaka, S., et al. (2012) Bile Acid Promotes Intestinal Metaplasia and Gastric Carcinogenesis. Cancer Epidemiology, Biomarkers & Prevention, 21, 2101-2107.
https://doi.org/10.1158/1055-9965.EPI-12-0730 |
| [14] | Chen, X.-Z., Hu, J.-K., Zhou, Z.-G., et al. (2010) Me-ta-Analysis of Effectiveness and Safety of D2 plus Para-Aortic Lymphadenectomy for Resectable Gastric Cancer. Jour-nal of the American College of Surgeons, 210, 100-105.
https://doi.org/10.1016/j.jamcollsurg.2009.09.033 |
| [15] | Seregni, E., Ferrari, L., Martinetti, A. and Bombardieri, E. (2001) Diagnostic and Prognostic Tumor Markers in the Gastrointestinal Tract. Seminars in Surgical Oncology, 20, 147-166. https://doi.org/10.1002/ssu.1028 |
| [16] | Chen, X.-Z., Yang, K., Zhang, B., Hu, J.-K. and Zhou, C. (2011) Is Retrieval of >25 Lymph Nodes a Superior Criterion for Locally Advanced Gastric Cancer Surgery? Annals of Surgery, 254, 834-835.
https://doi.org/10.1097/SLA.0b013e318235dfda |
| [17] | Chen, X.-Z., Yang, K., Liu, J., Chen, X.-L. and Hu, J.-K. (2011)) Neoadjuvant plus Adjuvant Chemotherapy Benefits Overall Survival of Locally Advanced Gastric Cancer. World Journal of Gastroenterology, 17, 4542-4544.
https://doi.org/10.3748/wjg.v17.i40.4542 |
| [18] | Duraker, N. and ？eli？k, A.N. (2001) The Prognostic Significance of Preoperative Serum CA 19-9 in Patients with Resectable Gastric Carcinoma: Comparison with CEA. Journal of Surgical Oncology, 76, 266-271.
https://doi.org/10.1002/jso.1044 |
| [19] | Louhimo, J., Kokkola, A., Alfthan, H., Stenman, U.-H. and Haglund, C. (2004) Preoperative hCGβ and CA 72-4 Are Prognostic Factors in Gastric Cancer. International Journal of Cancer, 111, 929-933. https://doi.org/10.1002/ijc.20321 |
| [20] | Fu, T., Coulter, S., Yoshihara, E., et al. (2019) FXR Regulates In-testinal Cancer Stem Cell Proliferation. Cell, 176, 1098-112. https://doi.org/10.1016/j.cell.2019.01.036 |
| [21] | Li, T., Guo, H., Li, H., et al. (2019) MicroRNA-92a-1-5p Increases CDX2 by Targeting FOXD1 in Bile Acids-Induced Gastric Intestinal Metaplasia. Gut, 68, 1751-1763. https://doi.org/10.1136/gutjnl-2017-315318 |
| [22] | Wu, L., Huang, P., Wang, F., et al. (2015) Relationship between Serum CA19-9 and CEA Levels and Prognosis of Pancreatic Cancer. An-nals of Translational Medicine, 3, Article No. 328. |
| [23] | Cook, J., Kennaway, E. and Kennaway, N. (1940) Production of Tumours in Mice by Deoxycholic Acid. Nature, 145, 627. https://doi.org/10.1038/145627a0 |
| [24] | Bernstein, H., Bernstein, C., Payne, C.M. and Dvorak, K. (2009) Bile Acids as Endogenous Etiologic Agents in Gastrointestinal Cancer. World Journal of Gastroenterology, 15, 3329-3340. https://doi.org/10.3748/wjg.15.3329 |
| [25] | Ocvirk, S. and O’Keefe, S.J.D. (2021) Dietary Fat, Bile Acid Metabolism and Colorectal Cancer. Seminars in Cancer Biology, 73, 347-355. https://doi.org/10.1016/j.semcancer.2020.10.003 |
| [26] | Li, D., Zhang, J., Yao, W., et al. (2020) The Rela-tionship between Gastric Cancer, Its Precancerous Lesions and Bile Reflux: A Retrospective Study. Journal of Digestive Diseases, 21, 222-229. https://doi.org/10.1111/1751-2980.12858 |
| [27] | Kim, D.H., Oh, S.J., Oh, C.A., et al. (2011) The Relationships between Perioperative CEA, CA 19-9, and CA 72-4 and Recurrence in Gastric Cancer Patients after Curative Radical Gastrectomy. Journal of Surgical Oncology, 104, 585-591. https://doi.org/10.1002/jso.21919 |
| [28] | Fan, B. and Xiong, B. (2011) Investigation of Serum Tumor Markers in the Diagnosis of Gastric Cancer. Hepato-Gastroenterology, 58, 239-245. |
