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The role of lactate deshydrogenase levels on non-small cell lung cancer prognosis: a meta-analysis
Corresponding Author(s) : Yan-Liang Qu
Cellular and Molecular Biology,
Vol. 65 No. 1: Issue 1
Abstract
The role of serum lactate dehydrogenase (LDH) on the clinical outcomes of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs) treatment remained to be elucidated. Therefore, we did this meta-analysis. We searched databases including PubMed, EMBASE, and Cochrane Library till to June, 2017. The relationships between the LDH levels and overall survival (OS) and progression free survival (PFS) were assessed by calculating hazard ratios (HRs) and 95% confidence intervals (CIs). The association between the LDH levels and disease control rate (DCR) was calculated by odds ratio (OR) and 95% CI. Seven studies were included in the meta-analysis. As for DCR, the result from this meta-analysis was not positive (OR=0.71; 95% CI 0.21 – 2.37; P=0.57). As for PFS, the result of the meta-analysis indicated that elevated LDH was significantly associated with shorter PFS (HR=1.88; 95%CI, 1.37–2.59). When studies were stratified by ethnicity, significant association was also observed in Asian group (HR=2.36; 95%CI, 1.57–3.55). As for OS, patients with high levels of LDH showed significantly shorter OS (HR=2.44; 95%CI, 1.84–3.23). In the subgroup by race, significant associations were found in Asian group (HR=2.62; 95%CI, 1.61–4.26) and Caucasian population (HR=2.36; 95%CI, 1.66–3.34). In conclusion, this meta-analysis suggested that elevated LDH level was associated with the poor PFS and OS of NSCLC patients receiving EGFR-TKIs treatment.
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- 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;66:115–132.
- Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 2008;83(5):584–594.
- Socinski MA, Evans T, Gettinger S, Hensing TA, VanDam SL, Ireland B, et al. Treatment of stage IV non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(Suppl 5):e341S–e368S.
- Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, et al. Spanish Lung Cancer Group in collaboration with Groupe Français de Pneumo-Cancérologie and Associazione Italiana Oncologia Toracica Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): A multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13:239–246.
- Suda K, Mitsudomi T. Role of EGFR mutations in lung cancers: prognosis and tumor chemosensitivity. Arch Toxicol. 2015;89(8):1227-40.
- Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, et al. North-East Japan Study Group Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010;362:2380–2388.
- Zhang X, Guo M, Fan J, Lv Z, Huang Q, Han J, Wu F, Hu G, Xu J, Jin Y. Prognostic significance of serum LDH in small cell lung cancer: A systematic review with meta-analysis. Cancer Biomark. 2016;16(3):415-23.
- Fiala O, Pesek M, Finek J, Topolcan O, Racek J, Svaton M, Kucera R, Minarik M, Benesova L, Bortlicek Z, Chloupkova R, Poprach A, Buchler T. Change in Serum Lactate Dehydrogenase Is Associated with Outcome of Patients with Advanced-stage NSCLC Treated with Erlotinib. Anticancer Res. 2016;36(5):2459-65.
- Inomata M, Hayashi R, Tanaka H, Shimokawa K, Tokui K, Taka C, Okazawa S, Kambara K, Ichikawa T, Yamada T, Miwa T, Kashii T, Matsui S, Tobe K. Elevated levels of plasma lactate dehydrogenase is an unfavorable prognostic factor in patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer, receiving treatment with gefitinib or erlotinib. Mol Clin Oncol. 2016;4(5):774-778.
- Shao L, Hong W, Zheng L, He C, Zhang B, Xie F, Song Z, Lou G, Zhang Y. Joint serum tumor markers serve as survival predictive model of erlotinib in the treatment of recurrent non-small cell lung cancer. Zhongguo Fei Ai Za Zhi. 2014;17(5):391-400.
- Krawczyk P, Kowalski DM, Krawczyk KW, Szczyrek M, Mlak R, Rolski A, Szudy A, Kieszko R, Winiarczyk K, Milanowski J, Krzakowski M. Predictive and prognostic factors in second- and third-line erlotinib treatment in NSCLC patients with known status of the EGFR gene. Oncol Rep. 2013;30(3):1463-72.
- Zhao LD, Li JL, Wang Y, Wang B, Wang HY, Hao XZ, Cui CX, Zhang XR, Shi YK. Factors affecting the sensitivity of EGFR-TKI treatment in advanced non-small cell lung cancer. Zhonghua Zhong Liu Za Zhi. 2011;33(3):217-21.
- Wojas-Krawczyk K, Krawczyk P, Mlak R, Kucharczyk T, Kowalski DM, Krzakowski M, Milanowski J. The applicability of a predictive index for second- and third-line treatment of unselected non-small-cell lung cancer patients. Respiration. 2011;82(4):341-50.
- Lee DS, Park KR, Kim SJ, Chung MJ, Lee YH, Chang JH, Kang JH, Hong SH, Kim MS, Kim YS. Serum lactate dehydrogenase levels at presentation in stage IV non-small cell lung cancer: predictive value of metastases and relation to survival outcomes. Tumour Biol. 2016;37:619-25.
- Kang MH, Go SI, Song HN, Lee A, Kim SH, Kang JH, Jeong BK, Kang KM, Ling H, Lee GW. The prognostic impact of the neutrophil-to-lymphocyte ratio in patients with small-cell lung cancer. Br J Cancer. 2014;111(3):452-60.
- Koukourakis MI, Giatromanolaki A, Sivridis E, Bougioukas G, Didilis V, Gatter KC, Harris AL; Tumour and Angiogenesis Research Group. Lactate dehydrogenase-5 (LDH-5) overexpression in non-small-cell lung cancer tissues is linked to tumour hypoxia, angiogenic factor production and poor prognosis. Br J Cancer. 2003;89(5):877-85.
- Danner BC, Didilis VN, Wiemeyer S, Stojanovic T, Kitz J, Emmert A, Füzesi L, Schöndube FA. Long-term survival is linked to serum LDH and partly to tumour LDH-5 in NSCLC. Anticancer Res. 2010;30(4):1347-51.
- Verma A, Phua CK, Sim WY, Algoso RE, Tee KS, Lew SJ, Lim AY, Goh SK, Tai DY, Kor AC, Ho B, Abisheganaden J. Pleural LDH as a prognostic marker in adenocarcinoma lung with malignant pleural effusion. Medicine (Baltimore). 2016;95:e3996.
References
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;66:115–132.
Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 2008;83(5):584–594.
Socinski MA, Evans T, Gettinger S, Hensing TA, VanDam SL, Ireland B, et al. Treatment of stage IV non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(Suppl 5):e341S–e368S.
Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, et al. Spanish Lung Cancer Group in collaboration with Groupe Français de Pneumo-Cancérologie and Associazione Italiana Oncologia Toracica Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): A multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13:239–246.
Suda K, Mitsudomi T. Role of EGFR mutations in lung cancers: prognosis and tumor chemosensitivity. Arch Toxicol. 2015;89(8):1227-40.
Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, et al. North-East Japan Study Group Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010;362:2380–2388.
Zhang X, Guo M, Fan J, Lv Z, Huang Q, Han J, Wu F, Hu G, Xu J, Jin Y. Prognostic significance of serum LDH in small cell lung cancer: A systematic review with meta-analysis. Cancer Biomark. 2016;16(3):415-23.
Fiala O, Pesek M, Finek J, Topolcan O, Racek J, Svaton M, Kucera R, Minarik M, Benesova L, Bortlicek Z, Chloupkova R, Poprach A, Buchler T. Change in Serum Lactate Dehydrogenase Is Associated with Outcome of Patients with Advanced-stage NSCLC Treated with Erlotinib. Anticancer Res. 2016;36(5):2459-65.
Inomata M, Hayashi R, Tanaka H, Shimokawa K, Tokui K, Taka C, Okazawa S, Kambara K, Ichikawa T, Yamada T, Miwa T, Kashii T, Matsui S, Tobe K. Elevated levels of plasma lactate dehydrogenase is an unfavorable prognostic factor in patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer, receiving treatment with gefitinib or erlotinib. Mol Clin Oncol. 2016;4(5):774-778.
Shao L, Hong W, Zheng L, He C, Zhang B, Xie F, Song Z, Lou G, Zhang Y. Joint serum tumor markers serve as survival predictive model of erlotinib in the treatment of recurrent non-small cell lung cancer. Zhongguo Fei Ai Za Zhi. 2014;17(5):391-400.
Krawczyk P, Kowalski DM, Krawczyk KW, Szczyrek M, Mlak R, Rolski A, Szudy A, Kieszko R, Winiarczyk K, Milanowski J, Krzakowski M. Predictive and prognostic factors in second- and third-line erlotinib treatment in NSCLC patients with known status of the EGFR gene. Oncol Rep. 2013;30(3):1463-72.
Zhao LD, Li JL, Wang Y, Wang B, Wang HY, Hao XZ, Cui CX, Zhang XR, Shi YK. Factors affecting the sensitivity of EGFR-TKI treatment in advanced non-small cell lung cancer. Zhonghua Zhong Liu Za Zhi. 2011;33(3):217-21.
Wojas-Krawczyk K, Krawczyk P, Mlak R, Kucharczyk T, Kowalski DM, Krzakowski M, Milanowski J. The applicability of a predictive index for second- and third-line treatment of unselected non-small-cell lung cancer patients. Respiration. 2011;82(4):341-50.
Lee DS, Park KR, Kim SJ, Chung MJ, Lee YH, Chang JH, Kang JH, Hong SH, Kim MS, Kim YS. Serum lactate dehydrogenase levels at presentation in stage IV non-small cell lung cancer: predictive value of metastases and relation to survival outcomes. Tumour Biol. 2016;37:619-25.
Kang MH, Go SI, Song HN, Lee A, Kim SH, Kang JH, Jeong BK, Kang KM, Ling H, Lee GW. The prognostic impact of the neutrophil-to-lymphocyte ratio in patients with small-cell lung cancer. Br J Cancer. 2014;111(3):452-60.
Koukourakis MI, Giatromanolaki A, Sivridis E, Bougioukas G, Didilis V, Gatter KC, Harris AL; Tumour and Angiogenesis Research Group. Lactate dehydrogenase-5 (LDH-5) overexpression in non-small-cell lung cancer tissues is linked to tumour hypoxia, angiogenic factor production and poor prognosis. Br J Cancer. 2003;89(5):877-85.
Danner BC, Didilis VN, Wiemeyer S, Stojanovic T, Kitz J, Emmert A, Füzesi L, Schöndube FA. Long-term survival is linked to serum LDH and partly to tumour LDH-5 in NSCLC. Anticancer Res. 2010;30(4):1347-51.
Verma A, Phua CK, Sim WY, Algoso RE, Tee KS, Lew SJ, Lim AY, Goh SK, Tai DY, Kor AC, Ho B, Abisheganaden J. Pleural LDH as a prognostic marker in adenocarcinoma lung with malignant pleural effusion. Medicine (Baltimore). 2016;95:e3996.