Skip to main content
Top
Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Biomarkers | Research article

Clinical use of tumor biomarkers in prediction for prognosis and chemotherapeutic effect in esophageal squamous cell carcinoma

Authors: Yuchong Yang, Xuanzhang Huang, Likun Zhou, Ting Deng, Tao Ning, Rui Liu, Le Zhang, Ming Bai, Haiyang Zhang, Hongli Li, Yi Ba

Published in: BMC Cancer | Issue 1/2019

Login to get access

Abstract

Background

Growing evidence has indicated that tumor biomarkers, including cytokeratin 19 fragment antigen 21–1 (Cyfra21–1), carbohydrate antigen 19–9 (CA19–9), carbohydrate antigen 72–4 (CA72–4), carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC-Ag) were reported to be commonly used in diagnosis and prognosis in esophageal squamous cell carcinoma (ESCC). However, which is the best marker for predicting prognosis remains unknown. Few papers focused on the relationship between tumor biomarkers and postoperative treatment in ESCC.

Methods

A total of 416 ESCC patients were enrolled in this study. The association between tumor markers and overall survival (OS) was analyzed using Kaplan-Meier method with log-rank test, followed by multivariate Cox regression models.

Results

The results of Cox multivariate analysis indicated that among these tumor biomarkers, CA19–9 (≥ 37 vs. < 37) [hazard ratio (HR) = 2.130, 95% confidence interval (CI) = 1.138–3.986, p = 0.018] and CEA (≥ 5 vs. < 5) (HR = 1.827, 95% CI = 1.089–3.064, p = 0.022) were the independent prognostic factors of poor OS. For the ESCC patients with CA19–9 < 37, CEA < 5 or SCC-Ag < 1.5, the surgery plus postoperative chemotherapy group had a significantly longer OS than the surgery group alone (p < 0.05), but this significant difference of OS between these two groups cannot be found in patients with CA19–9 ≥ 37, CEA ≥ 5 or SCC-Ag ≥ 1.5 (p > 0.05).

Conclusions

CEA and CA19–9 maybe are superior to other tumor biomarkers as prognostic indicators in ESCC. CA19–9, CEA, SCC-Ag may be useful in predicting the therapeutic effect of postoperative chemotherapy in ESCC.
Appendix
Available only for authorised users
Literature
1.
go back to reference Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–32.CrossRef Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–32.CrossRef
2.
go back to reference Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med. 2003;349(23):2241–52.CrossRef Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med. 2003;349(23):2241–52.CrossRef
3.
go back to reference Lin Y, Totsuka Y, He Y, Kikuchi S, Qiao Y, Ueda J, Wei W, Inoue M, Tanaka H. Epidemiology of esophageal cancer in Japan and China. J Epidemiol. 2013;23(4):233–42.CrossRef Lin Y, Totsuka Y, He Y, Kikuchi S, Qiao Y, Ueda J, Wei W, Inoue M, Tanaka H. Epidemiology of esophageal cancer in Japan and China. J Epidemiol. 2013;23(4):233–42.CrossRef
4.
go back to reference Ohashi S, Miyamoto S, Kikuchi O, Goto T, Amanuma Y, Muto M. Recent advances from basic and clinical studies of esophageal squamous cell carcinoma. Gastroenterology. 2015;149(7):1700–15.CrossRef Ohashi S, Miyamoto S, Kikuchi O, Goto T, Amanuma Y, Muto M. Recent advances from basic and clinical studies of esophageal squamous cell carcinoma. Gastroenterology. 2015;149(7):1700–15.CrossRef
5.
go back to reference Cao X, Zhang L, Feng GR, Yang J, Wang RY, Li J, Zheng XM, Han YJ. Preoperative Cyfra21-1 and SCC-ag serum titers predict survival in patients with stage II esophageal squamous cell carcinoma. J Transl Med. 2012;10:197.CrossRef Cao X, Zhang L, Feng GR, Yang J, Wang RY, Li J, Zheng XM, Han YJ. Preoperative Cyfra21-1 and SCC-ag serum titers predict survival in patients with stage II esophageal squamous cell carcinoma. J Transl Med. 2012;10:197.CrossRef
6.
go back to reference Morita T, Kikuchi T, Hashimoto S, Kobayashi Y, Tokue A. Cytokeratin-19 fragment (CYFRA 21-1) in bladder cancer. Eur Urol. 1997;32(2):237–44.PubMed Morita T, Kikuchi T, Hashimoto S, Kobayashi Y, Tokue A. Cytokeratin-19 fragment (CYFRA 21-1) in bladder cancer. Eur Urol. 1997;32(2):237–44.PubMed
7.
go back to reference Holdenrieder S, Wehnl B, Hettwer K, Simon K, Uhlig S, Dayyani F. Carcinoembryonic antigen and cytokeratin-19 fragments for assessment of therapy response in non-small cell lung cancer: a systematic review and meta-analysis. Br J Cancer. 2017;116(8):1037–45.CrossRef Holdenrieder S, Wehnl B, Hettwer K, Simon K, Uhlig S, Dayyani F. Carcinoembryonic antigen and cytokeratin-19 fragments for assessment of therapy response in non-small cell lung cancer: a systematic review and meta-analysis. Br J Cancer. 2017;116(8):1037–45.CrossRef
8.
go back to reference Bauer TM, El-Rayes BF, Li X, Hammad N, Philip PA, Shields AF, Zalupski MM, Bekaii-Saab T. Carbohydrate antigen 19-9 is a prognostic and predictive biomarker in patients with advanced pancreatic cancer who receive gemcitabine-containing chemotherapy: a pooled analysis of 6 prospective trials. Cancer. 2013;119(2):285–92.CrossRef Bauer TM, El-Rayes BF, Li X, Hammad N, Philip PA, Shields AF, Zalupski MM, Bekaii-Saab T. Carbohydrate antigen 19-9 is a prognostic and predictive biomarker in patients with advanced pancreatic cancer who receive gemcitabine-containing chemotherapy: a pooled analysis of 6 prospective trials. Cancer. 2013;119(2):285–92.CrossRef
9.
go back to reference Hamazoe R, Maeta M, Matsui T, Shibata S, Shiota S, Kaibara N. CA72-4 compared with carcinoembryonic antigen as a tumour marker for gastric cancer. Eur J Cancer. 1992;28A(8–9):1351–4.CrossRef Hamazoe R, Maeta M, Matsui T, Shibata S, Shiota S, Kaibara N. CA72-4 compared with carcinoembryonic antigen as a tumour marker for gastric cancer. Eur J Cancer. 1992;28A(8–9):1351–4.CrossRef
10.
go back to reference Duffy MJ. Carcinoembryonic antigen as a marker for colorectal cancer: is it clinically useful? Clin Chem. 2001;47(4):624–30.PubMed Duffy MJ. Carcinoembryonic antigen as a marker for colorectal cancer: is it clinically useful? Clin Chem. 2001;47(4):624–30.PubMed
11.
go back to reference Charakorn C, Thadanipon K, Chaijindaratana S, Rattanasiri S, Numthavaj P, Thakkinstian A. The association between serum squamous cell carcinoma antigen and recurrence and survival of patients with cervical squamous cell carcinoma: a systematic review and meta-analysis. Gynecol Oncol. 2018;150(1):190–200.CrossRef Charakorn C, Thadanipon K, Chaijindaratana S, Rattanasiri S, Numthavaj P, Thakkinstian A. The association between serum squamous cell carcinoma antigen and recurrence and survival of patients with cervical squamous cell carcinoma: a systematic review and meta-analysis. Gynecol Oncol. 2018;150(1):190–200.CrossRef
12.
go back to reference Zhang HQ, Wang RB, Yan HJ, Zhao W, Zhu KL, Jiang SM, Hu XG, Yu JM. Prognostic significance of CYFRA21-1, CEA and hemoglobin in patients with esophageal squamous cancer undergoing concurrent chemoradiotherapy. Asian Pac J Cancer Prev. 2012;13(1):199–203.CrossRef Zhang HQ, Wang RB, Yan HJ, Zhao W, Zhu KL, Jiang SM, Hu XG, Yu JM. Prognostic significance of CYFRA21-1, CEA and hemoglobin in patients with esophageal squamous cancer undergoing concurrent chemoradiotherapy. Asian Pac J Cancer Prev. 2012;13(1):199–203.CrossRef
13.
go back to reference Ikeguchi M, Kouno Y, Kihara K, Suzuki K, Endo K, Nakamura S, Sawada T, Shimizu T, Matsunaga T, Fukumoto Y, et al. Evaluation of prognostic markers for patients with curatively resected thoracic esophageal squamous cell carcinomas. Mol Clin Oncol. 2016;5(6):767–72.CrossRef Ikeguchi M, Kouno Y, Kihara K, Suzuki K, Endo K, Nakamura S, Sawada T, Shimizu T, Matsunaga T, Fukumoto Y, et al. Evaluation of prognostic markers for patients with curatively resected thoracic esophageal squamous cell carcinomas. Mol Clin Oncol. 2016;5(6):767–72.CrossRef
14.
go back to reference Kosugi S, Nishimaki T, Kanda T, Nakagawa S, Ohashi M, Hatakeyama K. Clinical significance of serum carcinoembryonic antigen, carbohydrate antigen 19-9, and squamous cell carcinoma antigen levels in esophageal cancer patients. World J Surg. 2004;28(7):680–5.CrossRef Kosugi S, Nishimaki T, Kanda T, Nakagawa S, Ohashi M, Hatakeyama K. Clinical significance of serum carcinoembryonic antigen, carbohydrate antigen 19-9, and squamous cell carcinoma antigen levels in esophageal cancer patients. World J Surg. 2004;28(7):680–5.CrossRef
15.
go back to reference Tokunaga R, Imamura Y, Nakamura K, Uchihara T, Ishimoto T, Nakagawa S, Iwatsuki M, Baba Y, Sakamoto Y, Miyamoto Y, et al. Carbohydrate antigen 19-9 is a useful prognostic marker in esophagogastric junction adenocarcinoma. Cancer Med. 2015;4(11):1659–66.CrossRef Tokunaga R, Imamura Y, Nakamura K, Uchihara T, Ishimoto T, Nakagawa S, Iwatsuki M, Baba Y, Sakamoto Y, Miyamoto Y, et al. Carbohydrate antigen 19-9 is a useful prognostic marker in esophagogastric junction adenocarcinoma. Cancer Med. 2015;4(11):1659–66.CrossRef
16.
go back to reference Oki S, Toiyama Y, Okugawa Y, Shimura T, Okigami M, Yasuda H, Fujikawa H, Okita Y, Yoshiyama S, Hiro J, et al. Clinical burden of preoperative albumin-globulin ratio in esophageal cancer patients. Am J Surg. 2017;214(5):891–8.CrossRef Oki S, Toiyama Y, Okugawa Y, Shimura T, Okigami M, Yasuda H, Fujikawa H, Okita Y, Yoshiyama S, Hiro J, et al. Clinical burden of preoperative albumin-globulin ratio in esophageal cancer patients. Am J Surg. 2017;214(5):891–8.CrossRef
17.
go back to reference Hulscher JB, van Sandick JW, de Boer AG, Wijnhoven BP, Tijssen JG, Fockens P, Stalmeier PF, ten Kate FJ, van Dekken H, Obertop H, et al. Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the esophagus. N Engl J Med. 2002;347(21):1662–9.CrossRef Hulscher JB, van Sandick JW, de Boer AG, Wijnhoven BP, Tijssen JG, Fockens P, Stalmeier PF, ten Kate FJ, van Dekken H, Obertop H, et al. Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the esophagus. N Engl J Med. 2002;347(21):1662–9.CrossRef
18.
go back to reference Yan HJ, Wang RB, Zhu KL, Jiang SM, Zhao W, Xu XQ, Feng R. Cytokeratin 19 fragment antigen 21-1 as an independent predictor for definitive chemoradiotherapy sensitivity in esophageal squamous cell carcinoma. Chin Med J. 2012;125(8):1410–5.PubMed Yan HJ, Wang RB, Zhu KL, Jiang SM, Zhao W, Xu XQ, Feng R. Cytokeratin 19 fragment antigen 21-1 as an independent predictor for definitive chemoradiotherapy sensitivity in esophageal squamous cell carcinoma. Chin Med J. 2012;125(8):1410–5.PubMed
19.
go back to reference Shimada H, Nabeya Y, Okazumi S, Matsubara H, Shiratori T, Gunji Y, Kobayashi S, Hayashi H, Ochiai T. Prediction of survival with squamous cell carcinoma antigen in patients with resectable esophageal squamous cell carcinoma. Surgery. 2003;133(5):486–94.CrossRef Shimada H, Nabeya Y, Okazumi S, Matsubara H, Shiratori T, Gunji Y, Kobayashi S, Hayashi H, Ochiai T. Prediction of survival with squamous cell carcinoma antigen in patients with resectable esophageal squamous cell carcinoma. Surgery. 2003;133(5):486–94.CrossRef
20.
go back to reference Yi Y, Li B, Sun H, Zhang Z, Gong H, Li H, Huang W, Wang Z. Predictors of sensitivity to chemoradiotherapy of esophageal squamous cell carcinoma. Tumour Biol. 2010;31(4):333–40.CrossRef Yi Y, Li B, Sun H, Zhang Z, Gong H, Li H, Huang W, Wang Z. Predictors of sensitivity to chemoradiotherapy of esophageal squamous cell carcinoma. Tumour Biol. 2010;31(4):333–40.CrossRef
21.
go back to reference Yi Y, Li B, Wang Z, Sun H, Gong H, Zhang Z. CYFRA21-1 and CEA are useful markers for predicting the sensitivity to chemoradiotherapy of esophageal squamous cell carcinoma. Biomarkers. 2009;14(7):480–5.CrossRef Yi Y, Li B, Wang Z, Sun H, Gong H, Zhang Z. CYFRA21-1 and CEA are useful markers for predicting the sensitivity to chemoradiotherapy of esophageal squamous cell carcinoma. Biomarkers. 2009;14(7):480–5.CrossRef
22.
go back to reference Okamura A, Watanabe M, Mine S, Kurogochi T, Yamashita K, Hayami M, Imamura Y, Ogura M, Ichimura T, Takahari D, et al. Failure of neoadjuvant chemotherapy for resectable esophageal squamous cell carcinoma. Dis Esophagus. 2017;30(9):1–8.CrossRef Okamura A, Watanabe M, Mine S, Kurogochi T, Yamashita K, Hayami M, Imamura Y, Ogura M, Ichimura T, Takahari D, et al. Failure of neoadjuvant chemotherapy for resectable esophageal squamous cell carcinoma. Dis Esophagus. 2017;30(9):1–8.CrossRef
Metadata
Title
Clinical use of tumor biomarkers in prediction for prognosis and chemotherapeutic effect in esophageal squamous cell carcinoma
Authors
Yuchong Yang
Xuanzhang Huang
Likun Zhou
Ting Deng
Tao Ning
Rui Liu
Le Zhang
Ming Bai
Haiyang Zhang
Hongli Li
Yi Ba
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-019-5755-5

Other articles of this Issue 1/2019

BMC Cancer 1/2019 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine