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Erschienen in: Gastric Cancer 4/2019

01.07.2019 | Original Article

Prognostic significance of serum alkaline phosphatase and lactate dehydrogenase levels in patients with unresectable advanced gastric cancer

verfasst von: Tsutomu Namikawa, Nobuko Ishida, Sachi Tsuda, Kazune Fujisawa, Eri Munekage, Jun Iwabu, Masaya Munekage, Sunao Uemura, Shigehiro Tsujii, Takahiko Tamura, Tomoaki Yatabe, Hiromichi Maeda, Hiroyuki Kitagawa, Michiya Kobayashi, Kazuhiro Hanazaki

Erschienen in: Gastric Cancer | Ausgabe 4/2019

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Abstract

Background

This study evaluated the prognostic value of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) together with host-related factors in patients with unresectable advanced gastric cancer.

Methods

The study enrolled 262 patients who received chemotherapy for unresectable advanced gastric cancer at Kochi Medical School from 2007 to 2015. Clinicopathological information and systemic inflammatory response data were analyzed for associations between baseline cancer-related prognostic variables and survival outcomes.

Results

The median survival time was significantly lower for patients with high ALP, high LDH, high total bilirubin, high aspartate aminotransferase, high alanine transaminase, high gamma-glutamyltransferase, high creatinine, a Glasgow prognostic score (GPS) of 1 or 2 score compared to GPS 0, higher compared to lower neutrophil to lymphocyte ratio (NLR) 3.9, lower compared to higher prognostic nutrition index 36.1, T3–4 compared to T1–2 tumor and diffuse-type compared to intestinal-type histology. Multivariate survival analysis identified high ALP 322 (HR 1.808; 95% CI 1.015–3.220; P = 0.044), T2–3 (HR 2.622; 95% CI 1.224–5.618; P = 0.013), and diffuse-type gastric cancer (HR 2.325; 95% CI 1.341–4.032; P = 0.003) as significant independent predictors of worse prognosis in the studied group of cancer patients.

Conclusions

High level of ALP is an independent, worse prognosis factor for patients receiving chemotherapy for unresectable and recurrent gastric cancer.
Literatur
1.
Zurück zum Zitat Nashimoto A, Akazawa K, Isobe Y, Miyashiro I, Katai H, Kodera Y, et al. Gastric cancer treated in 2002 in Japan: 2009 annual report of the JGCA nationwide registry. Gastric Cancer. 2013;16:1–27.CrossRefPubMed Nashimoto A, Akazawa K, Isobe Y, Miyashiro I, Katai H, Kodera Y, et al. Gastric cancer treated in 2002 in Japan: 2009 annual report of the JGCA nationwide registry. Gastric Cancer. 2013;16:1–27.CrossRefPubMed
2.
Zurück zum Zitat Fidler MM, Gupta S, Soerjomataram I, Ferlay J, Steliarova-Foucher E, Bray F. Cancer incidence and mortality among young adults aged 20–39 years worldwide in 2012: a population-based study. Lancet Oncol. 2017;18:1579–89.CrossRefPubMed Fidler MM, Gupta S, Soerjomataram I, Ferlay J, Steliarova-Foucher E, Bray F. Cancer incidence and mortality among young adults aged 20–39 years worldwide in 2012: a population-based study. Lancet Oncol. 2017;18:1579–89.CrossRefPubMed
3.
Zurück zum Zitat Ohtsu A, Yoshida S, Saijo N. Disparities in gastric cancer chemotherapy between the east and west. J Clin Oncol. 2006;24:2188–96.CrossRefPubMed Ohtsu A, Yoshida S, Saijo N. Disparities in gastric cancer chemotherapy between the east and west. J Clin Oncol. 2006;24:2188–96.CrossRefPubMed
4.
Zurück zum Zitat Ferreira LM1, Hebrant A, Dumont JE. Metabolic reprogramming of the tumor. Oncogene. 2012;31:3999–4011.CrossRefPubMed Ferreira LM1, Hebrant A, Dumont JE. Metabolic reprogramming of the tumor. Oncogene. 2012;31:3999–4011.CrossRefPubMed
6.
Zurück zum Zitat Fantin VR, St-Pierre J, Leder P. Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell. 2006;9:425–34.CrossRefPubMed Fantin VR, St-Pierre J, Leder P. Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell. 2006;9:425–34.CrossRefPubMed
7.
Zurück zum Zitat Wei XL, Zhang DS, He MM, Jin Y, Wang DS, Zhou YX, et al. The predictive value of alkaline phosphatase and lactate dehydrogenase for overall survival in patients with esophageal squamous cell carcinoma. Tumour Biol. 2016;37:1879–87.CrossRefPubMed Wei XL, Zhang DS, He MM, Jin Y, Wang DS, Zhou YX, et al. The predictive value of alkaline phosphatase and lactate dehydrogenase for overall survival in patients with esophageal squamous cell carcinoma. Tumour Biol. 2016;37:1879–87.CrossRefPubMed
8.
Zurück zum Zitat Ji F, Fu SJ, Guo ZY, Pang H, Ju WQ, Wang DP, et al. Prognostic value of combined preoperative lactate dehydrogenase and alkaline phosphatase levels in patients with resectable pancreatic ductal adenocarcinoma. Medicine (Baltimore). 2016;95:e4065.CrossRef Ji F, Fu SJ, Guo ZY, Pang H, Ju WQ, Wang DP, et al. Prognostic value of combined preoperative lactate dehydrogenase and alkaline phosphatase levels in patients with resectable pancreatic ductal adenocarcinoma. Medicine (Baltimore). 2016;95:e4065.CrossRef
9.
Zurück zum Zitat Namikawa T, Munekage E, Munekage M, Maeda H, Yatabe T, Kitagawa H, et al. Evaluation of systemic inflammatory response biomarkers in patients receiving chemotherapy for unresectable and recurrent advanced gastric cancer. Oncology. 2016;90(6):321–6.CrossRefPubMed Namikawa T, Munekage E, Munekage M, Maeda H, Yatabe T, Kitagawa H, et al. Evaluation of systemic inflammatory response biomarkers in patients receiving chemotherapy for unresectable and recurrent advanced gastric cancer. Oncology. 2016;90(6):321–6.CrossRefPubMed
10.
Zurück zum Zitat McMillan DC, Crozier JE, Canna K, Angerson WJ, McArdle CS. Evaluation of an inflammation-based prognostic score (GPS) in patients undergoing resection for colon and rectal cancer. Int J Colorectal Dis. 2007;22:881–6.CrossRefPubMed McMillan DC, Crozier JE, Canna K, Angerson WJ, McArdle CS. Evaluation of an inflammation-based prognostic score (GPS) in patients undergoing resection for colon and rectal cancer. Int J Colorectal Dis. 2007;22:881–6.CrossRefPubMed
11.
Zurück zum Zitat Wen J, Bedford M, Begum R, Mitchell H, Hodson J, Whiting J, et al. The value of inflammation based prognostic scores in patients undergoing surgical resection for oesophageal and gastric carcinoma. J Surg Oncol. 2018;117(8):1697–707.CrossRefPubMed Wen J, Bedford M, Begum R, Mitchell H, Hodson J, Whiting J, et al. The value of inflammation based prognostic scores in patients undergoing surgical resection for oesophageal and gastric carcinoma. J Surg Oncol. 2018;117(8):1697–707.CrossRefPubMed
12.
Zurück zum Zitat Tokunaga R, Sakamoto Y, Nakagawa S, Izumi D, Kosumi K, Taki K, et al. Comparison of systemic inflammatory and nutritional scores in colorectal cancer patients who underwent potentially curative resection. Int J Clin Oncol. 2017;22:740–8.CrossRefPubMed Tokunaga R, Sakamoto Y, Nakagawa S, Izumi D, Kosumi K, Taki K, et al. Comparison of systemic inflammatory and nutritional scores in colorectal cancer patients who underwent potentially curative resection. Int J Clin Oncol. 2017;22:740–8.CrossRefPubMed
13.
Zurück zum Zitat Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97.CrossRefPubMed Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97.CrossRefPubMed
14.
Zurück zum Zitat Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, et al. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008;9:215–21.CrossRefPubMed Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, et al. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008;9:215–21.CrossRefPubMed
15.
Zurück zum Zitat Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, Sawaki A, et al. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study. Lancet Oncol. 2009;10:1063–9.CrossRefPubMed Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, Sawaki A, et al. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study. Lancet Oncol. 2009;10:1063–9.CrossRefPubMed
16.
Zurück zum Zitat Xu XS, Wan Y, Song SD, Chen W, Miao RC, Zhou YY, et al. Model based on γ-glutamyltransferase and alkaline phosphatase for hepatocellular carcinoma prognosis. World J Gastroenterol. 2014;20:10944–52.CrossRefPubMedPubMedCentral Xu XS, Wan Y, Song SD, Chen W, Miao RC, Zhou YY, et al. Model based on γ-glutamyltransferase and alkaline phosphatase for hepatocellular carcinoma prognosis. World J Gastroenterol. 2014;20:10944–52.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Li G, Gao J, Tao YL, Xu BQ, Tu ZW, Liu ZG, et al. Increased pretreatment levels of serum LDH and ALP as poor prognostic factors for nasopharyngeal carcinoma. Chin J Cancer. 2012;31:197–206.CrossRefPubMedPubMedCentral Li G, Gao J, Tao YL, Xu BQ, Tu ZW, Liu ZG, et al. Increased pretreatment levels of serum LDH and ALP as poor prognostic factors for nasopharyngeal carcinoma. Chin J Cancer. 2012;31:197–206.CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Faloppi L, Bianconi M, Giampieri R, Sobrero A, Labianca R, Ferrari D, et al. The value of lactate dehydrogenase serum levels as a prognostic and predictive factor for advanced pancreatic cancer patients receiving sorafenib. Oncotarget. 2015;6:35087–94.CrossRefPubMedPubMedCentral Faloppi L, Bianconi M, Giampieri R, Sobrero A, Labianca R, Ferrari D, et al. The value of lactate dehydrogenase serum levels as a prognostic and predictive factor for advanced pancreatic cancer patients receiving sorafenib. Oncotarget. 2015;6:35087–94.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Yu MC, Chan KM, Lee CF, Lee YS, Eldeen FZ, Chou HS, et al. Alkaline phosphatase: does it have a role in predicting hepatocellular carcinoma recurrence? J Gastrointest Surg. 2011;15:1440–9.CrossRefPubMed Yu MC, Chan KM, Lee CF, Lee YS, Eldeen FZ, Chou HS, et al. Alkaline phosphatase: does it have a role in predicting hepatocellular carcinoma recurrence? J Gastrointest Surg. 2011;15:1440–9.CrossRefPubMed
20.
Zurück zum Zitat Hirschhaeuser F, Sattler UG, Mueller-Klieser W. Metabolic key player in cancer. Cancer Res. 2011;71:6921–5.CrossRefPubMed Hirschhaeuser F, Sattler UG, Mueller-Klieser W. Metabolic key player in cancer. Cancer Res. 2011;71:6921–5.CrossRefPubMed
21.
Zurück zum Zitat Tokumitsu S, 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.PubMed Tokumitsu S, 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.PubMed
22.
Zurück zum Zitat Kojima Y, Sakurada T. Increase in alkaline phosphatase activity in the liver of mice bearing Ehrlich ascites tumor. Cancer Res. 1976;36:23–7.PubMed Kojima Y, Sakurada T. Increase in alkaline phosphatase activity in the liver of mice bearing Ehrlich ascites tumor. Cancer Res. 1976;36:23–7.PubMed
23.
Zurück zum Zitat Dua P, Kang HS, Hong SM, Tsao MS, Kim S, Lee DK. Alkaline phosphatase ALPPL-2 is a novel pancreatic carcinoma-associated protein. Cancer Res. 2013;73(6):1934–45.CrossRefPubMed Dua P, Kang HS, Hong SM, Tsao MS, Kim S, Lee DK. Alkaline phosphatase ALPPL-2 is a novel pancreatic carcinoma-associated protein. Cancer Res. 2013;73(6):1934–45.CrossRefPubMed
25.
Zurück zum Zitat Kolev Y, Uetake H, Takagi Y, Sugihara K. Lactate dehydrogenase-5 (LDH-5) expression in human gastric cancer: association with hypoxia-inducible factor (HIF-1alpha) pathway, angiogenic factors production and poor prognosis. Ann Surg Oncol. 2008;15:2336–44.CrossRefPubMed Kolev Y, Uetake H, Takagi Y, Sugihara K. Lactate dehydrogenase-5 (LDH-5) expression in human gastric cancer: association with hypoxia-inducible factor (HIF-1alpha) pathway, angiogenic factors production and poor prognosis. Ann Surg Oncol. 2008;15:2336–44.CrossRefPubMed
26.
Zurück zum Zitat Wang H, Xing XM, Ma LN, Liu L, Hao J, Feng LX, et al. Metastatic lymph node ratio and Lauren classification are independent prognostic markers for survival rates of patients with gastric cancer. Oncol Lett. 2018;15:8853–62.PubMedPubMedCentral Wang H, Xing XM, Ma LN, Liu L, Hao J, Feng LX, et al. Metastatic lymph node ratio and Lauren classification are independent prognostic markers for survival rates of patients with gastric cancer. Oncol Lett. 2018;15:8853–62.PubMedPubMedCentral
27.
Zurück zum Zitat Berlth F, Bollschweiler E, Drebber U, Hoelscher AH, Moenig S. Pathohistological classification systems in gastric cancer: diagnostic relevance and prognostic value. World J Gastroenterol. 2014;20(19):5679–84.CrossRefPubMedPubMedCentral Berlth F, Bollschweiler E, Drebber U, Hoelscher AH, Moenig S. Pathohistological classification systems in gastric cancer: diagnostic relevance and prognostic value. World J Gastroenterol. 2014;20(19):5679–84.CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Mönig S, Baldus SE, Collet PH, Zirbes TK, Bollschweiler E, Thiele J, et al. Histological grading in gastric cancer by Goseki classification: correlation with histopathological subtypes and prognosis. Anticancer Res. 2001;21(1B):617–20.PubMed Mönig S, Baldus SE, Collet PH, Zirbes TK, Bollschweiler E, Thiele J, et al. Histological grading in gastric cancer by Goseki classification: correlation with histopathological subtypes and prognosis. Anticancer Res. 2001;21(1B):617–20.PubMed
29.
Zurück zum Zitat Forrest LM, McMillan DC, McArdle CS, Angerson WJ, Dunlop DJ. Evaluation of cumulative prognostic scores based on the systemic inflammatory response in patients with inoperable non-small-cell lung cancer. Br J Cancer. 2003;89(6):1028–30.CrossRefPubMedPubMedCentral Forrest LM, McMillan DC, McArdle CS, Angerson WJ, Dunlop DJ. Evaluation of cumulative prognostic scores based on the systemic inflammatory response in patients with inoperable non-small-cell lung cancer. Br J Cancer. 2003;89(6):1028–30.CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Proctor MJ, Morrison DS, Talwar D, Balmer SM, O’Reilly DS, Foulis AK, et al. An inflammation-based prognostic score (mGPS) predicts cancer survival independent of tumour site: a Glasgow Inflammation Outcome Study. Br J Cancer. 2011;104(4):726–34.CrossRefPubMedPubMedCentral Proctor MJ, Morrison DS, Talwar D, Balmer SM, O’Reilly DS, Foulis AK, et al. An inflammation-based prognostic score (mGPS) predicts cancer survival independent of tumour site: a Glasgow Inflammation Outcome Study. Br J Cancer. 2011;104(4):726–34.CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Sugimoto K, Komiyama H, Kojima Y, Goto M, Tomiki Y, Sakamoto K. Glasgow prognostic score as a prognostic factor in patients undergoing curative surgery for colorectal cancer. Dig Surg. 2012;29(6):503–9.CrossRefPubMed Sugimoto K, Komiyama H, Kojima Y, Goto M, Tomiki Y, Sakamoto K. Glasgow prognostic score as a prognostic factor in patients undergoing curative surgery for colorectal cancer. Dig Surg. 2012;29(6):503–9.CrossRefPubMed
32.
Zurück zum Zitat Kitagawa H, Namikawa T, Munekage M, Fujisawa K, Kawanishi Y, Kobayashi M, et al. Preoperative patient-related factors associated with prognosis after esophagectomy for esophageal cancer. Esophagus. 2017;14(4):360–5.CrossRef Kitagawa H, Namikawa T, Munekage M, Fujisawa K, Kawanishi Y, Kobayashi M, et al. Preoperative patient-related factors associated with prognosis after esophagectomy for esophageal cancer. Esophagus. 2017;14(4):360–5.CrossRef
33.
Zurück zum Zitat Brown DJ, Milroy R, Preston T, McMillan DC. The relationship between an inflammation-based prognostic score (Glasgow Prognostic Score) and changes in serum biochemical variables in patients with advanced lung and gastrointestinal cancer. J Clin Pathol. 2007;60(6):705–8.CrossRefPubMed Brown DJ, Milroy R, Preston T, McMillan DC. The relationship between an inflammation-based prognostic score (Glasgow Prognostic Score) and changes in serum biochemical variables in patients with advanced lung and gastrointestinal cancer. J Clin Pathol. 2007;60(6):705–8.CrossRefPubMed
Metadaten
Titel
Prognostic significance of serum alkaline phosphatase and lactate dehydrogenase levels in patients with unresectable advanced gastric cancer
verfasst von
Tsutomu Namikawa
Nobuko Ishida
Sachi Tsuda
Kazune Fujisawa
Eri Munekage
Jun Iwabu
Masaya Munekage
Sunao Uemura
Shigehiro Tsujii
Takahiko Tamura
Tomoaki Yatabe
Hiromichi Maeda
Hiroyuki Kitagawa
Michiya Kobayashi
Kazuhiro Hanazaki
Publikationsdatum
01.07.2019
Verlag
Springer Singapore
Erschienen in
Gastric Cancer / Ausgabe 4/2019
Print ISSN: 1436-3291
Elektronische ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-018-0897-8

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