Abstract
The elevation of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) has been demonstrated to predict worse prognosis in various malignancies; however, their prognostic value in esophageal squamous cell carcinoma has not been well studied. We conducted a retrospective study of 906 patients with esophageal squamous cell carcinoma to explore their prognostic value for overall survival. The optimal cutoff points for ALP and LDH were determined. We analyzed the association between the levels of ALP and LDH and clinicopathological characteristics. Their prognostic value for overall survival was explored by univariate and multivariate analysis. We also proposed the ALP and LDH classification and examined its prognostic value in the general population and subgroups. The optimal cutoff points of ALP and LDH to predict overall survival were 90.7 and 361.5 U/L respectively. Higher levels of ALP and LDH were both associated with more advanced TNM stage (P = 0.003 and 0.002, respectively) and more distant metastasis (P = 0.001 and P < 0.001, respectively). Both ALP (≤90.7/>90.7 U/L) and LDH (≤361.5/>361.5 U/L) were independent prognostic factors for overall survival in esophageal squamous cell carcinoma (P = 0.004 and P < 0.001 by multivariate analysis). The ALP and LDH classification categorized patients into three subgroups with distinct prognosis (P < 0.001 by multivariate analysis) and identified a small group of patients who had extremely poor overall survival with a median of 4.2 months. In conclusion, ALP and LDH were both independent prognostic factors for overall survival. A combination of the two indexes might contribute to further identification of survival differences in esophageal squamous cell carcinoma.
Similar content being viewed by others
References
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, vol. 23, 2013:233–42.
Arnold M, Soerjomataram I, Ferlay J, Forman D. Global incidence of oesophageal cancer by histological subtype in 2012. Gut 2014.
Rice TW, Rusch VW, Ishwaran H, Blackstone EH. Cancer of the esophagus and esophagogastric junction: data-driven staging for the seventh edition of the American Joint Committee on Cancer/International Union Against Cancer Cancer Staging Manuals. Cancer. 2010;116:3763–73.
Maisano R, Azzarello D, Del MP, Maisano M, Bottari M, Egitto G, et al. Alkaline phosphatase levels as a prognostic factor in metastatic colorectal cancer treated with the FOLFOX 4 regimen: a monoinstitutional retrospective study. Tumori. 2011;97:39–42.
Sonpavde G, Pond GR, Berry WR, de Wit R, Armstrong AJ, Eisenberger MA, et al. Serum alkaline phosphatase changes predict survival independent of PSA changes in men with castration-resistant prostate cancer and bone metastasis receiving chemotherapy. Urol Oncol. 2012;30:607–13.
Xie W, Nakabayashi M, Regan MM, Oh WK. Higher prostate-specific antigen levels predict improved survival in patients with hormone-refractory prostate cancer who have skeletal metastases and normal serum alkaline phosphatase. Cancer. 2007;110:2709–15.
Xie Y, Wei ZB, Duan XW. Prognostic value of pretreatment serum alkaline phosphatase in nasopharyngeal carcinoma. Asian Pac J Cancer Prev. 2014;15:3547–53.
Sagman U, Feld R, Evans WK, Warr D, Shepherd FA, Payne D, et al. The prognostic significance of pretreatment serum lactate dehydrogenase in patients with small-cell lung cancer. J Clin Oncol. 1991;9:954–61.
Armstrong AJ, George DJ, Halabi S. Serum lactate dehydrogenase predicts for overall survival benefit in patients with metastatic renal cell carcinoma treated with inhibition of mammalian target of rapamycin. J Clin Oncol. 2012;30:3402–7.
Brown JE, Cook RJ, Lipton A, Coleman RE. Serum lactate dehydrogenase is prognostic for survival in patients with bone metastases from breast cancer: a retrospective analysis in bisphosphonate-treated patients. Clin Cancer Res. 2012;18:6348–55.
Wei Z, Zeng X, Xu J, Duan X, Xie Y. Prognostic value of pretreatment serum levels of lactate dehydrogenase in nonmetastatic nasopharyngeal carcinoma: single-site analysis of 601 patients in a highly endemic area. Onco Targets Ther. 2014;7:739–49.
Yamada Y, Nakamura K, Aoki S, Tobiume M, Zennami K, Kato Y, et al. Lactate dehydrogenase, Gleason score and HER-2 overexpression are significant prognostic factors for M1b prostate cancer. Oncol Rep. 2011;25:937–44.
Huang JJ, Cai MY, Ye S, Li ZM, Huang HQ, Lin TY. Clinical analysis of 19 cases of subcutaneous panniculitis T-cell lymphoma with literature review. Ai Zheng. 2009;28:1093–9.
Chau I, Norman AR, Cunningham D, Waters JS, Oates J, Ross PJ. Multivariate prognostic factor analysis in locally advanced and metastatic esophago-gastric cancer—pooled analysis from three multicenter, randomized, controlled trials using individual patient data. J Clin Oncol. 2004;22:2395–403.
Polee MB, Hop WC, Kok TC, Eskens FA, van der Burg ME, Splinter TA, et al. Prognostic factors for survival in patients with advanced oesophageal cancer treated with cisplatin-based combination chemotherapy. Br J Cancer. 2003;89:2045–50.
Alici S, Ugras S, Bayram I, Izmirli M. Prognostic factors and COX-2 expression in advanced stage esophageal squamous cell carcinoma. Adv Ther. 2006;23:672–9.
Zhang P, Xi M, Li QQ, He LR, Liu SL, Zhao L, et al. The modified Glasgow prognostic score is an independent prognostic factor in patients with inoperable thoracic esophageal squamous cell carcinoma undergoing chemoradiotherapy. J Cancer Educ. 2014;5:689–95.
Budczies J, Klauschen F, Sinn BV, Gyorffy B, Schmitt WD, Darb-Esfahani S, et al. Cutoff finder: a comprehensive and straightforward Web application enabling rapid biomarker cutoff optimization. PLoS One. 2012;7, e51862.
Zhang SS, Yang H, Luo KJ, Huang QY, Chen JY, Yang F, et al. The impact of body mass index on complication and survival in resected oesophageal cancer: a clinical-based cohort and meta-analysis. Br J Cancer. 2013;109:2894–903.
Feng JF, Chen QX. Significance of the prognostic nutritional index in patients with esophageal squamous cell carcinoma. Ther Clin Risk Manag. 2014;10:1–7.
Feng JF, Huang Y, Liu JS. Combination of neutrophil lymphocyte ratio and platelet lymphocyte ratio is a useful predictor of postoperative survival in patients with esophageal squamous cell carcinoma. Onco Targets Ther. 2013;6:1605–12.
Turen S, Ozyar E, Altundag K, Gullu I, Atahan IL. Serum lactate dehydrogenase level is a prognostic factor in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy. Cancer Investig. 2007;25:315–21.
Weiss MJ, Ray K, Henthorn PS, Lamb B, Kadesch T, Harris H. Structure of the human liver/bone/kidney alkaline phosphatase gene. J Biol Chem. 1988;263:12002–10.
Xu XS, Wan Y, Song SD, Chen W, Miao RC, Zhou YY, et al. Model based on gamma-glutamyltransferase and alkaline phosphatase for hepatocellular carcinoma prognosis. World J Gastroenterol. 2014;20:10944–52.
Leung TW, Tang AM, Zee B, Lau WY, Lai PB, Leung KL, et al. Construction of the Chinese University Prognostic Index for hepatocellular carcinoma and comparison with the TNM staging system, the Okuda staging system, and the Cancer of the Liver Italian Program staging system: a study based on 926 patients. Cancer. 2002;94:1760–9.
Zhang M, Yan X, Zhang F. Expression of placental alkaline phosphatase in esophageal cancer cell line Eca109. Zhonghua Zhong Liu Za Zhi. 1996;18:186–8.
Ali NN, Rowe J, Teich NM. Constitutive expression of non-bone/liver/kidney alkaline phosphatase in human osteosarcoma cell lines. J Bone Miner Res. 1996;11:512–20.
Tokumitsu SI, Tokumitsu K, Kohnoe K, Takeuchi T. Characterization of liver-type alkaline phosphatase from human gastric carcinoma cells (KMK-2) in vitro. Cancer Res. 1979;39:4732–8.
Burrell RA, Swanton C. Tumour heterogeneity and the evolution of polyclonal drug resistance. Mol Oncol. 2014;8:1095–111.
Kogo M, Suzuki A, Kaneko K, Yoneyama K, Imawari M, Kiuchi Y. Scoring system for predicting response to chemoradiotherapy, including 5-fluorouracil and platinum, for patients with esophageal cancer. Dig Dis Sci. 2008;53:2415–21.
Doherty JR, Cleveland JL. Targeting lactate metabolism for cancer therapeutics. J Clin Invest. 2013;123:3685–92.
Baggstrom MQ, Qi Y, Koczywas M, Argiris A, Johnson EA, Millward MJ, et al. A phase II study of AT-101 (Gossypol) in chemotherapy-sensitive recurrent extensive-stage small cell lung cancer. J Thorac Oncol. 2011;6:1757–60.
Liu G, Kelly WK, Wilding G, Leopold L, Brill K, Somer B. An open-label, multicenter, phase I/II study of single-agent AT-101 in men with castrate-resistant prostate cancer. Clin Cancer Res. 2009;15:3172–6.
Han X, Sheng X, Jones HM, Jackson AL, Kilgore J, Stine JE, et al. Evaluation of the anti-tumor effects of lactate dehydrogenase inhibitor galloflavin in endometrial cancer cells. J Hematol Oncol. 2015;8:2.
Acknowledgments
This work was supported by The National Natural Science Foundation of China (No. 81372570), The Science and Technology Department of Guangdong Province, China (No. 2012B031800088), and The Science and Technology Department of Guangdong Province, China (No. C2011019). We gratefully thank all the staff members in our department for their support and suggestion in this study.
Author information
Authors and Affiliations
Corresponding author
Additional information
Xiao-li Wei and Dong-sheng Zhang contributed equally to this work.
Rights and permissions
About this article
Cite this article
Wei, Xl., Zhang, Ds., He, Mm. et al. The predictive value of alkaline phosphatase and lactate dehydrogenase for overall survival in patients with esophageal squamous cell carcinoma. Tumor Biol. 37, 1879–1887 (2016). https://doi.org/10.1007/s13277-015-3851-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-015-3851-y