Skip to main content
Top
Published in: BMC Cancer 1/2021

Open Access 01-12-2021 | Rituximab | Research article

Prognostic significance of pretreatment serum free fatty acid in patients with diffuse large B-cell lymphoma in the rituximab era: a retrospective analysis

Authors: Liping Fan, Qiuyan Lin, Xiaoling Huang, Danhui Fu, Haobo Huang

Published in: BMC Cancer | Issue 1/2021

Login to get access

Abstract

Background

Fatty acid metabolism is reportedly associated with various cancers. However, the role of pretreatment serum free fatty acid (FFA) levels in diffuse large B-cell lymphoma (DLBCL) prognosis is still unclear, and our study aimed to better elucidate its influence on clinical outcomes.

Methods

The medical records of 221 newly diagnosed DLBCL patients admitted to Fujian Medical University Union Hospital from January 2011 to December 2016 were analysed retrospectively. Receiver operating characteristic curve analysis was used to determine a cut-off value for pretreatment serum FFA levels for prognostic prediction in DLBCL patients. The relationship between pretreatment serum FFA levels and clinical and laboratory parameters was analysed. Univariate and multivariate analyses were used to assess prognostic factors for overall survival (OS) and progression-free survival (PFS).

Results

Newly diagnosed DLBCL patients with high pretreatment serum FFA levels (≥0.495 mmol/l) had more B symptoms, higher serum lactate dehydrogenase levels (> upper limit of normal), >1 extranodal site, and higher International Prognostic Index score (3–5) compared to those with low pretreatment serum FFA levels (<0.495 mmol/l). Higher serum FFA levels were independent prognostic factors for poor OS, but not PFS.

Conclusions

High pretreatment serum FFA levels are associated with lower survival in untreated DLBCL patients.
Literature
1.
go back to reference Crump M, Neelapu SS, Farooq U, Van Den Neste E, Kuruvilla J, Westin J, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800–8.CrossRef Crump M, Neelapu SS, Farooq U, Van Den Neste E, Kuruvilla J, Westin J, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800–8.CrossRef
2.
go back to reference Ayers EC, Li S, Medeiros LJ, Bond DA, Maddocks KJ, Torka P, et al. Outcomes in patients with aggressive B-cell non-Hodgkin lymphoma after intensive frontline treatment failure. Cancer. 2020;126(2):293–303.CrossRef Ayers EC, Li S, Medeiros LJ, Bond DA, Maddocks KJ, Torka P, et al. Outcomes in patients with aggressive B-cell non-Hodgkin lymphoma after intensive frontline treatment failure. Cancer. 2020;126(2):293–303.CrossRef
3.
go back to reference Swerdlow SHCE, Harris NL, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2008. Swerdlow SHCE, Harris NL, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2008.
4.
go back to reference Zhou Z, Sehn LH, Rademaker AW, Gordon LI, Lacasce AS, Crosby-Thompson A, et al. An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era. Blood. 2014;123(6):837–42.CrossRef Zhou Z, Sehn LH, Rademaker AW, Gordon LI, Lacasce AS, Crosby-Thompson A, et al. An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era. Blood. 2014;123(6):837–42.CrossRef
5.
go back to reference Sehn LH, Berry B, Chhanabhai M, Fitzgerald C, Gill K, Hoskins P, et al. The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood. 2007;109(5):1857–61.CrossRef Sehn LH, Berry B, Chhanabhai M, Fitzgerald C, Gill K, Hoskins P, et al. The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood. 2007;109(5):1857–61.CrossRef
6.
go back to reference Ruppert AS, Dixon JG, Salles G, Wall A, Cunningham D, Poeschel V, et al. International prognostic indices in diffuse large B-cell lymphoma: a comparison of IPI, R-IPI, and NCCN-IPI. Blood. 2020;135(23):2041–8.CrossRef Ruppert AS, Dixon JG, Salles G, Wall A, Cunningham D, Poeschel V, et al. International prognostic indices in diffuse large B-cell lymphoma: a comparison of IPI, R-IPI, and NCCN-IPI. Blood. 2020;135(23):2041–8.CrossRef
7.
go back to reference Montalban C, Diaz-Lopez A, Dlouhy I, Rovira J, Lopez-Guillermo A, Alonso S, et al. Validation of the NCCN-IPI for diffuse large B-cell lymphoma (DLBCL): the addition of beta2 -microglobulin yields a more accurate GELTAMO-IPI. Br J Haematol. 2017;176(6):918–28.CrossRef Montalban C, Diaz-Lopez A, Dlouhy I, Rovira J, Lopez-Guillermo A, Alonso S, et al. Validation of the NCCN-IPI for diffuse large B-cell lymphoma (DLBCL): the addition of beta2 -microglobulin yields a more accurate GELTAMO-IPI. Br J Haematol. 2017;176(6):918–28.CrossRef
8.
go back to reference Upadhyay M, Samal J, Kandpal M, Singh OV, Vivekanandan P. The Warburg effect: insights from the past decade. Pharmacol Ther. 2013;137(3):318–30.CrossRef Upadhyay M, Samal J, Kandpal M, Singh OV, Vivekanandan P. The Warburg effect: insights from the past decade. Pharmacol Ther. 2013;137(3):318–30.CrossRef
9.
go back to reference Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.CrossRef Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.CrossRef
10.
go back to reference Gao R, Liang JH, Wang L, Zhu HY, Wu W, Cao L, et al. Low serum cholesterol levels predict inferior prognosis and improve NCCN-IPI scoring in diffuse large B cell lymphoma. Int J Cancer. 2018;143(8):1884–95.CrossRef Gao R, Liang JH, Wang L, Zhu HY, Wu W, Cao L, et al. Low serum cholesterol levels predict inferior prognosis and improve NCCN-IPI scoring in diffuse large B cell lymphoma. Int J Cancer. 2018;143(8):1884–95.CrossRef
11.
go back to reference Barre FPY, Claes BSR, Dewez F, Peutz-Kootstra C, Munch-Petersen HF, Gronbaek K, et al. Specific Lipid and Metabolic Profiles of R-CHOP-Resistant Diffuse Large B-Cell Lymphoma Elucidated by Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging and in Vivo Imaging. Anal Chem. 2018;90(24):14198–206.CrossRef Barre FPY, Claes BSR, Dewez F, Peutz-Kootstra C, Munch-Petersen HF, Gronbaek K, et al. Specific Lipid and Metabolic Profiles of R-CHOP-Resistant Diffuse Large B-Cell Lymphoma Elucidated by Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging and in Vivo Imaging. Anal Chem. 2018;90(24):14198–206.CrossRef
12.
go back to reference Zhou X, Mei H, Agee J, Brown T, Mao J. Racial differences in distribution of fatty acids in prostate cancer and benign prostatic tissues. Lipids Health Dis. 2019;18(1):189.CrossRef Zhou X, Mei H, Agee J, Brown T, Mao J. Racial differences in distribution of fatty acids in prostate cancer and benign prostatic tissues. Lipids Health Dis. 2019;18(1):189.CrossRef
13.
go back to reference Zhang L, Han L, He J, Lv J, Pan R, Lv T. A high serum-free fatty acid level is associated with cancer. J Cancer Res Clin Oncol. 2020;146(3):705–10.CrossRef Zhang L, Han L, He J, Lv J, Pan R, Lv T. A high serum-free fatty acid level is associated with cancer. J Cancer Res Clin Oncol. 2020;146(3):705–10.CrossRef
14.
go back to reference Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25(5):579–86.CrossRef Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25(5):579–86.CrossRef
15.
go back to reference Zelenetz AD, Wierda WG, Abramson JS, Advani RH, Andreadis CB, Bartlett N, et al. Non-Hodgkin's lymphomas, version 1.2013. J Natl Compr Canc Netw. 2013;11(3):257–72.CrossRef Zelenetz AD, Wierda WG, Abramson JS, Advani RH, Andreadis CB, Bartlett N, et al. Non-Hodgkin's lymphomas, version 1.2013. J Natl Compr Canc Netw. 2013;11(3):257–72.CrossRef
16.
go back to reference Zelenetz AD, Abramson JS, Advani RH, Andreadis CB, Byrd JC, Czuczman MS, et al. NCCN Clinical Practice Guidelines in Oncology: non-Hodgkin's lymphomas. J Natl Compr Canc Netw. 2010;8(3):288–334.CrossRef Zelenetz AD, Abramson JS, Advani RH, Andreadis CB, Byrd JC, Czuczman MS, et al. NCCN Clinical Practice Guidelines in Oncology: non-Hodgkin's lymphomas. J Natl Compr Canc Netw. 2010;8(3):288–334.CrossRef
17.
go back to reference Horwitz SM, Zelenetz AD, Gordon LI, Wierda WG, Abramson JS, Advani RH, et al. NCCN Guidelines Insights: Non-Hodgkin's Lymphomas, Version 3.2016. J Natl Compr Canc Netw. 2016;14(9):1067–79.CrossRef Horwitz SM, Zelenetz AD, Gordon LI, Wierda WG, Abramson JS, Advani RH, et al. NCCN Guidelines Insights: Non-Hodgkin's Lymphomas, Version 3.2016. J Natl Compr Canc Netw. 2016;14(9):1067–79.CrossRef
18.
go back to reference Andersen CJ, Dupree L, Murray K, Ragonesi N, McMullen K, Cintron-Rivera L, et al. Low-Density Lipoproteins, High-Density Lipoproteins (HDL), and HDL-Associated Proteins Differentially Modulate Chronic Myelogenous Leukemia Cell Viability. Lipids. 2020;55(6):615–26.CrossRef Andersen CJ, Dupree L, Murray K, Ragonesi N, McMullen K, Cintron-Rivera L, et al. Low-Density Lipoproteins, High-Density Lipoproteins (HDL), and HDL-Associated Proteins Differentially Modulate Chronic Myelogenous Leukemia Cell Viability. Lipids. 2020;55(6):615–26.CrossRef
19.
go back to reference Choi S, Yoo YJ, Kim H, Lee H, Chung H, Nam MH, et al. Clinical and biochemical relevance of monounsaturated fatty acid metabolism targeting strategy for cancer stem cell elimination in colon cancer. Biochem Biophys Res Commun. 2019;519(1):100–5.CrossRef Choi S, Yoo YJ, Kim H, Lee H, Chung H, Nam MH, et al. Clinical and biochemical relevance of monounsaturated fatty acid metabolism targeting strategy for cancer stem cell elimination in colon cancer. Biochem Biophys Res Commun. 2019;519(1):100–5.CrossRef
20.
go back to reference Cvetkovic Z, Milosevic M, Cvetkovic B, Masnikosa R, Arsic A, Petrovic S, et al. Plasma phospholipid changes are associated with response to chemotherapy in non-Hodgkin lymphoma patients. Leuk Res. 2017;54:39–46.CrossRef Cvetkovic Z, Milosevic M, Cvetkovic B, Masnikosa R, Arsic A, Petrovic S, et al. Plasma phospholipid changes are associated with response to chemotherapy in non-Hodgkin lymphoma patients. Leuk Res. 2017;54:39–46.CrossRef
21.
go back to reference Downes DP, Daurio NA, McLaren DG, Carrington P, Previs SF, Williams KB. Impact of Extracellular Fatty Acids and Oxygen Tension on Lipid Synthesis and Assembly in Pancreatic Cancer Cells. ACS Chem Biol. 2020;15(7):1892–900.CrossRef Downes DP, Daurio NA, McLaren DG, Carrington P, Previs SF, Williams KB. Impact of Extracellular Fatty Acids and Oxygen Tension on Lipid Synthesis and Assembly in Pancreatic Cancer Cells. ACS Chem Biol. 2020;15(7):1892–900.CrossRef
22.
go back to reference Li J, Gu D, Lee SS, Song B, Bandyopadhyay S, Chen S, et al. Abrogating cholesterol esterification suppresses growth and metastasis of pancreatic cancer. Oncogene. 2016;35(50):6378–88.CrossRef Li J, Gu D, Lee SS, Song B, Bandyopadhyay S, Chen S, et al. Abrogating cholesterol esterification suppresses growth and metastasis of pancreatic cancer. Oncogene. 2016;35(50):6378–88.CrossRef
23.
go back to reference Madak-Erdogan Z, Band S, Zhao YC, Smith BP, Kulkoyluoglu-Cotul E, Zuo Q, et al. Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling. Cancer Res. 2019;79(10):2494–510.PubMed Madak-Erdogan Z, Band S, Zhao YC, Smith BP, Kulkoyluoglu-Cotul E, Zuo Q, et al. Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling. Cancer Res. 2019;79(10):2494–510.PubMed
24.
go back to reference Mulas MF, Abete C, Pulisci D, Pani A, Massidda B, Dessi S, et al. Cholesterol esters as growth regulators of lymphocytic leukaemia cells. Cell Prolif. 2011;44(4):360–71.CrossRef Mulas MF, Abete C, Pulisci D, Pani A, Massidda B, Dessi S, et al. Cholesterol esters as growth regulators of lymphocytic leukaemia cells. Cell Prolif. 2011;44(4):360–71.CrossRef
25.
go back to reference Cheng S, Wang G, Wang Y, Cai L, Qian K, Ju L, et al. Fatty acid oxidation inhibitor etomoxir suppresses tumor progression and induces cell cycle arrest via PPARgamma-mediated pathway in bladder cancer. Clin Sci (Lond). 2019;133(15):1745–58.CrossRef Cheng S, Wang G, Wang Y, Cai L, Qian K, Ju L, et al. Fatty acid oxidation inhibitor etomoxir suppresses tumor progression and induces cell cycle arrest via PPARgamma-mediated pathway in bladder cancer. Clin Sci (Lond). 2019;133(15):1745–58.CrossRef
26.
go back to reference Hanikoglu A, Kucuksayan E, Hanikoglu F, Ozben T, Menounou G, Sansone A, et al. Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes. Anticancer Agents Med Chem. 2019;19(15):1899–909.CrossRef Hanikoglu A, Kucuksayan E, Hanikoglu F, Ozben T, Menounou G, Sansone A, et al. Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes. Anticancer Agents Med Chem. 2019;19(15):1899–909.CrossRef
27.
go back to reference Nguyen PA, Chang CC, Galvin CJ, Wang YC, Yeon An S, Huang CW, et al. Statins use and its impact in EGFR-TKIs resistance to prolong the survival of lung cancer patients: A Cancer Registry Cohort Study in Taiwan. Cancer Sci. 2020;111(8):2965–73.CrossRef Nguyen PA, Chang CC, Galvin CJ, Wang YC, Yeon An S, Huang CW, et al. Statins use and its impact in EGFR-TKIs resistance to prolong the survival of lung cancer patients: A Cancer Registry Cohort Study in Taiwan. Cancer Sci. 2020;111(8):2965–73.CrossRef
28.
go back to reference Rink JS, Yang S, Cen O, Taxter T, McMahon KM, Misener S, et al. Rational Targeting of Cellular Cholesterol in Diffuse Large B-Cell Lymphoma (DLBCL) Enabled by Functional Lipoprotein Nanoparticles: A Therapeutic Strategy Dependent on Cell of Origin. Mol Pharm. 2017;14(11):4042–51.CrossRef Rink JS, Yang S, Cen O, Taxter T, McMahon KM, Misener S, et al. Rational Targeting of Cellular Cholesterol in Diffuse Large B-Cell Lymphoma (DLBCL) Enabled by Functional Lipoprotein Nanoparticles: A Therapeutic Strategy Dependent on Cell of Origin. Mol Pharm. 2017;14(11):4042–51.CrossRef
29.
go back to reference Smyth L, Blunt DN, Gatov E, Nagamuthu C, Croxford R, Mozessohn L, et al. Statin and cyclooxygenase-2 inhibitors improve survival in newly diagnosed diffuse large B-cell lymphoma: a large population-based study of 4913 subjects. Br J Haematol. 2020;191(3):396–404.CrossRef Smyth L, Blunt DN, Gatov E, Nagamuthu C, Croxford R, Mozessohn L, et al. Statin and cyclooxygenase-2 inhibitors improve survival in newly diagnosed diffuse large B-cell lymphoma: a large population-based study of 4913 subjects. Br J Haematol. 2020;191(3):396–404.CrossRef
30.
go back to reference Trotta F, Avena P, Chimento A, Rago V, De Luca A, Sculco S, et al. Statins reduce intratumor cholesterol affecting adrenocortical cancer growth. Mol Cancer Ther. 2020;19(9):1909–21.CrossRef Trotta F, Avena P, Chimento A, Rago V, De Luca A, Sculco S, et al. Statins reduce intratumor cholesterol affecting adrenocortical cancer growth. Mol Cancer Ther. 2020;19(9):1909–21.CrossRef
31.
go back to reference Tutuska K, Parrilla-Monge L, Di Cesare E, Nemajerova A, Moll UM. Statin as anti-cancer therapy in autochthonous T-lymphomas expressing stabilized gain-of-function mutant p53 proteins. Cell Death Dis. 2020;11(4):274.CrossRef Tutuska K, Parrilla-Monge L, Di Cesare E, Nemajerova A, Moll UM. Statin as anti-cancer therapy in autochthonous T-lymphomas expressing stabilized gain-of-function mutant p53 proteins. Cell Death Dis. 2020;11(4):274.CrossRef
32.
go back to reference Peixoto J, Lima J. Metabolic traits of cancer stem cells. Dis Model Mech. 2018;11(8):dmm033464.CrossRef Peixoto J, Lima J. Metabolic traits of cancer stem cells. Dis Model Mech. 2018;11(8):dmm033464.CrossRef
33.
go back to reference Amiri M, Yousefnia S, Seyed Forootan F, Peymani M, Ghaedi K, Nasr Esfahani MH. Diverse roles of fatty acid binding proteins (FABPs) in development and pathogenesis of cancers. Gene. 2018;676:171–83.CrossRef Amiri M, Yousefnia S, Seyed Forootan F, Peymani M, Ghaedi K, Nasr Esfahani MH. Diverse roles of fatty acid binding proteins (FABPs) in development and pathogenesis of cancers. Gene. 2018;676:171–83.CrossRef
34.
go back to reference Zhao L, Hao F, Huang J, Liu X, Ma X, Wang C, et al. Sex- and Age-Related Metabolic Characteristics of Serum Free Fatty Acids in Healthy Chinese Adults. J Proteome Res. 2020;19(4):1383–91.CrossRef Zhao L, Hao F, Huang J, Liu X, Ma X, Wang C, et al. Sex- and Age-Related Metabolic Characteristics of Serum Free Fatty Acids in Healthy Chinese Adults. J Proteome Res. 2020;19(4):1383–91.CrossRef
35.
go back to reference Thanarajasingam G, Maurer MJ, Habermann TM, Nowakowski GS, Bennani NN, Thompson CA, et al. Low Plasma Omega-3 Fatty Acid Levels May Predict Inferior Prognosis in Untreated Diffuse Large B-Cell Lymphoma: A New Modifiable Dietary Biomarker? Nutr Cancer. 2018;70(7):1088–90.CrossRef Thanarajasingam G, Maurer MJ, Habermann TM, Nowakowski GS, Bennani NN, Thompson CA, et al. Low Plasma Omega-3 Fatty Acid Levels May Predict Inferior Prognosis in Untreated Diffuse Large B-Cell Lymphoma: A New Modifiable Dietary Biomarker? Nutr Cancer. 2018;70(7):1088–90.CrossRef
Metadata
Title
Prognostic significance of pretreatment serum free fatty acid in patients with diffuse large B-cell lymphoma in the rituximab era: a retrospective analysis
Authors
Liping Fan
Qiuyan Lin
Xiaoling Huang
Danhui Fu
Haobo Huang
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-021-08963-6

Other articles of this Issue 1/2021

BMC Cancer 1/2021 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