Low serum albumin levels and high neutrophil counts are predictive of a poorer prognosis in patients with metastatic breast cancer

Xiang,Mengqi; Xiang,Mengqi; Zhang,Huachuan; Zhang,Huachuan; Tian,Jinjun; Tian,Jinjun; Yuan,Yihang; Yuan,Yihang; Xu,Zhihua; Xu,Zhihua; Chen,Jing; Chen,Jing

doi:10.3892/ol.2022.13552

Low serum albumin levels and high neutrophil counts are predictive of a poorer prognosis in patients with metastatic breast cancer

Authors:
- Mengqi Xiang
- Huachuan Zhang
- Jinjun Tian
- Yihang Yuan
- Zhihua Xu
- Jing Chen
View Affiliations

Affiliations: Department of Medical Oncology, Sichuan Cancer Hospital, Medical School of University of Electronic Science and Technology of China, Chengdu, Sichuan 610041, P.R. China, Department of Thoracic Surgery, Sichuan Cancer Hospital, Medical School of University of Electronic Science and Technology of China, Chengdu, Sichuan 610041, P.R. China, Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China, Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
Published online on: October 19, 2022 https://doi.org/10.3892/ol.2022.13552
Article Number: 432
Copyright: © Xiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Breast cancer is a severe disease with high incidence and mortality rates in menopausal women. Previous studies have shown that nutritional status and inflammation play a significant role in the development of breast cancer. However, whether serum albumin (ALB) and neutrophils (NE) accelerate the progression of this disease remains unclear. In the present study, a total of 94 cases of newly diagnosed metastatic breast cancer were assessed. For analysis, 26 risk factors including ALB and NE were assessed. Multivariate Cox proportional hazards regression analysis was then used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for continuous and categorical covariates. Compared with the control group, patients with disease progression, low levels of ALB, higher NE, counts, and higher neutrophil to lymphocyte ratio counts were associated with worse overall survival (OS). When these risk factors were fitted into a multivariate regression model, progression [P<0.001, HR=3.03 (1.62‑5.66)], NE counts ≥3.370x109 [P=0.004, HR=2.15 (1.27‑3.65)] and ALB levels <43.275 g/l [P=0.008, HR=0.47 (0.27‑0.82)] remained statistically significant factors for a worse OS. These independently associated risk factors were used to form an OS estimation nomogram. The constructed nomogram demonstrated good accuracy in estimating risk, with a bootstrap‑corrected C index of 0.686. We further collected data on 30 patients for external validation and found the nomogram had an accuracy of 83.3%. In conclusion, low serum ALB levels and increased NE counts were predictive of a poorer prognosis in patients with metastatic breast cancer. Nomograms based on the multivariate analysis showed a good predictive ability for estimating the risk of OS.

View Figures

View References

1	Siegel RL, Miller KD and Jemal A: Cancer Statistics, 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI
2	Esteva FJ, Hubbard-Lucey VM, Tang J and Pusztai L: Immunotherapy and targeted therapy combinations in metastatic breast cancer. Lancet Oncol. 20:e175–e186. 2019. View Article : Google Scholar : PubMed/NCBI
3	Stehle G, Sinn H, Wunder A, Schrenk HH, Stewart JC, Hartung G, Maier-Borst W and Heene DL: Plasma protein (albumin) catabolism by the tumor itself-implications for tumor metabolism and the genesis of cachexia. Crit Rev Oncol Hematol. 26:77–100. 1997. View Article : Google Scholar : PubMed/NCBI
4	Coates RJ, Clark WS, Eley JW, Greenberg RS, Huguley CM Jr and Brown RL: Race, nutritional status, and survival from breast cancer. J Natl Cancer Inst. 82:1684–1692. 1990. View Article : Google Scholar : PubMed/NCBI
5	Cohen MP: Clinical, pathophysiological and structure/function consequences of modification of albumin by Amadori-glucose adducts. Biochim Biophys Acta. 1830:5480–5485. 2013. View Article : Google Scholar : PubMed/NCBI
6	Hoogenboezem EN and Duvall CL: Harnessing albumin as a carrier for cancer therapies. Adv Drug Deliv Rev. 130:73–89. 2018. View Article : Google Scholar : PubMed/NCBI
7	Lee JL, Oh ES, Lee RW and Finucane TE: Serum albumin and prealbumin in calorically restricted, nondiseased individuals: A systematic review. Am J Med. 128:1023e1–22. 2015. View Article : Google Scholar : PubMed/NCBI
8	Liu Z and Chen X: Simple bioconjugate chemistry serves great clinical advances: Albumin as a versatile platform for diagnosis and precision therapy. Chem Soc Rev. 45:1432–1456. 2016. View Article : Google Scholar : PubMed/NCBI
9	Selfridge JM, Sinner HF, Whiting J, Sun W, Mallory MA, Hoover SJ, Kiluk JV, Khakpour N, Czerniecki BJ, Laronga C, et al: Effect of microporous polysaccharide particles in patients undergoing mastectomy. Clin Breast Cancer. S1526-8209(22)00177-X 2022 (Epub ahead of print). PubMed/NCBI
10	Wu S, Xin Z, Sui D, Ou Z, Bai H, Zhu S, Wang X and Zhang J: Development and validation of a nomogram to predict drainage duration in patients with breast cancer treated with modified radical mastectomy. Sci Rep. 11:25332021. View Article : Google Scholar : PubMed/NCBI
11	Latorre A, Latorre A, Castellanos M, Rodriguez Diaz C, Lazaro-Carrillo A, Aguado T, Lecea M, Romero-Pérez S, Calero M, Sanchez-Puelles JM, et al: Multifunctional albumin-stabilized gold nanoclusters for the reduction of cancer stem cells. Cancers (Basel). 11:9692019. View Article : Google Scholar : PubMed/NCBI
12	Mantovani A: The yin-yang of tumor-associated neutrophils. Cancer Cell. 16:173–174. 2009. View Article : Google Scholar : PubMed/NCBI
13	Todoric J and Karin M: The Fire within: Cell-Autonomous Mechanisms in Inflammation-Driven Cancer. Cancer Cell. 35:714–720. 2019. View Article : Google Scholar : PubMed/NCBI
14	Yang L and Lin PC: Mechanisms that drive inflammatory tumor microenvironment, tumor heterogeneity, and metastatic progression. Semin Cancer Biol. 47:185–195. 2017. View Article : Google Scholar : PubMed/NCBI
15	Glennon-Alty L, Hackett AP, Chapman EA and Wright HL: Neutrophils and redox stress in the pathogenesis of autoimmune disease. Free Radic Biol Med. 125:25–35. 2018. View Article : Google Scholar : PubMed/NCBI
16	Aiyappa-Maudsley R, Elsalem L, Ibrahim AIM, Pors K and Martin SG: In vitro radiosensitization of breast cancer with hypoxia-activated prodrugs. J Cell Mol Med. 26:4577–4590. 2022. View Article : Google Scholar : PubMed/NCBI
17	Ramirez-Moreno IG, Ibarra-Sanchez A, Castillo-Arellano JI, Blank U and Gonzalez-Espinosa C: Mast cells localize in hypoxic zones of tumors and secrete CCL-2 under Hypoxia through Activation of L-type calcium channels. J Immunol. 204:1056–1068. 2020. View Article : Google Scholar : PubMed/NCBI
18	Kong B, Li M, Gao B, Han B, Zhao Z and Wang F: Retracted Article: Overexpression of circ_0034642 contributes to hypoxia-induced glycolysis, cell proliferation, migration and invasion in gliomas by facilitating TAGLN2 expression via sponging miR-625-5p. RSC Adv. 10:897–908. 2020. View Article : Google Scholar : PubMed/NCBI
19	Ding Y and Xue L: The potential value of fibrinogen to albumin ratio (FAR) in the assessment of inflammation in spondyloarthritis. BMC Musculoskelet Disord. 23:8642022. View Article : Google Scholar : PubMed/NCBI
20	Hara K, Aoyama T, Yamada T, Nakazono M, Nagasawa S, Shimoda Y, Kumazu Y, Numata M, Hayashi T, Tamagawa H, et al: The prognostic value of the perioperative systemic inflammation score for patients with advanced gastric cancer. Anticancer Res. 40:1503–1512. 2020. View Article : Google Scholar : PubMed/NCBI
21	Ikeguchi M, Hanaki T, Endo K, Suzuki K, Nakamura S, Sawata T and Shimizu T: C-Reactive Protein/albumin ratio and prognostic nutritional index are strong prognostic indicators of survival in resected pancreatic ductal adenocarcinoma. J Pancreat Cancer. 3:31–36. 2017. View Article : Google Scholar : PubMed/NCBI
22	Artigas A, Wernerman J, Arroyo V, Vincent JL and Levy M: Role of albumin in diseases associated with severe systemic inflammation: Pathophysiologic and clinical evidence in sepsis and in decompensated cirrhosis. J Crit Care. 33:62–70. 2016. View Article : Google Scholar : PubMed/NCBI
23	Don BR and Kaysen G: Serum albumin: Relationship to inflammation and nutrition. Semin Dial. 17:432–437. 2004. View Article : Google Scholar : PubMed/NCBI
24	Frye S, Butterfield R and Hoffman JM: SNMMI clinical trials network research series for technologists: Ethical issues and regulations in the medical workplace. J Nucl Med Technol. 49:303–310. 2021. View Article : Google Scholar : PubMed/NCBI
25	Morote J, Aguilar A, Planas J and Trilla E: Definition of castrate resistant prostate cancer: New Insights. Biomedicines. 10:6892022. View Article : Google Scholar : PubMed/NCBI
26	Chinese Association of Breast Surgery, . A consensus statement on the breast-conserving surgery of early-stage breast cancer (2019). Zhonghua Wai Ke Za Zhi. 57:81–84. 2019.(In Chinese). PubMed/NCBI
27	Kim H: Propensity score analysis in non-randomized experimental designs: An overview and a tutorial using R software. New Dir Child Adolesc Dev. 2019:65–89. 2019. View Article : Google Scholar : PubMed/NCBI
28	Zhou ZR, Wang WW, Li Y, Jin KR, Wang XY, Wang ZW, Chen YS, Wang SJ, Hu J, Zhang HN, et al: In-depth mining of clinical data: The construction of clinical prediction model with R. Ann Transl Med. 7:7962019. View Article : Google Scholar : PubMed/NCBI
29	Sarett SM, Werfel TA, Lee L, Jackson MA, Kilchrist KV, Brantley-Sieders D and Duvall CL: Lipophilic siRNA targets albumin in situ and promotes bioavailability, tumor penetration, and carrier-free gene silencing. Proc Natl Acad Sci USA. 114:E6490–E6497. 2017. View Article : Google Scholar : PubMed/NCBI
30	Wang X. Han H, Duan Q, Khan U, Hu Y and Yao X: Changes of serum albumin level and systemic inflammatory response in inoperable non-small cell lung cancer patients after chemotherapy. J Cancer Res Ther. 10:1019–1023. 2014. View Article : Google Scholar : PubMed/NCBI
31	Bozzetti F, Migliavacca S, Scotti A, Bonalumi MG, Scarpa D, Baticci F, Ammatuna M, Pupa A, Terno G, Sequeira C, et al: Impact of cancer, type, site, stage and treatment on the nutritional status of patients. Ann Surg. 196:170–179. 1982. View Article : Google Scholar : PubMed/NCBI
32	Chen J, Zhou Y, Xu Y, Zhu HY and Shi YQ: Low pretreatment serum globulin may predict favorable prognosis for gastric cancer patients. Tumour Biol. 37:3905–3911. 2016. View Article : Google Scholar : PubMed/NCBI
33	Liu X, Meng QH, Ye Y, Hildebrandt MA, Gu J and Wu X: Prognostic significance of pretreatment serum levels of albumin, LDH and total bilirubin in patients with non-metastatic breast cancer. Carcinogenesis. 36:243–248. 2015. View Article : Google Scholar : PubMed/NCBI
34	Lis CG, Grutsch JF, Vashi PG and Lammersfeld CA: Is serum albumin an independent predictor of survival in patients with breast cancer? JPEN J Parenter Enteral Nutr. 27:10–15. 2003. View Article : Google Scholar : PubMed/NCBI
35	Mantovani A: The inflammation-cancer connection. FEBS J. 285:638–640. 2018. View Article : Google Scholar : PubMed/NCBI
36	Sun H, Hu P, Shen H, Dong W, Zhang T, Liu Q and Du J: Albumin and neutrophil combined prognostic grade as a new prognostic factor in non-small cell lung cancer: Results from a large consecutive cohort. PLoS One. 10:e01446632015. View Article : Google Scholar : PubMed/NCBI
37	Dumitru CA, Lang S and Brandau S: Modulation of neutrophil granulocytes in the tumor microenvironment: Mechanisms and consequences for tumor progression. Semin Cancer Biol. 23:141–148. 2013. View Article : Google Scholar : PubMed/NCBI
38	Dumitru CA, Gholaman H, Trellakis S, Bruderek K, Dominas N, Gu X, Bankfalvi A, Whiteside TL, Lang S and Brandau S: Tumor-derived macrophage migration inhibitory factor modulates the biology of head and neck cancer cells via neutrophil activation. Int J Cancer. 129:859–869. 2011. View Article : Google Scholar : PubMed/NCBI
39	Kaplan MJ and Radic M: Neutrophil extracellular traps: Double-edged swords of innate immunity. J Immunol. 189:2689–2695. 2012. View Article : Google Scholar : PubMed/NCBI
40	Manzo A, Sforza V, Carillio G, Palumbo G, Montanino A, Sandomenico C, Costanzo R, Esposito G, Laudato F, Mercadante E, et al: Lurbinectedin in small cell lung cancer. Front Oncol. 12:9321052022. View Article : Google Scholar : PubMed/NCBI
41	Yang ZY, Liu L, Mao C, Wu XY, Huang YF, Hu XF and Tang JL: Chemotherapy with cetuximab versus chemotherapy alone for chemotherapy-naive advanced non-small cell lung cancer. Cochrane Database Syst Rev CD009948, . 2014. View Article : Google Scholar
42	Mhaskar R, Clark OA, Lyman G, Engel Ayer Botrel T, Morganti Paladini L and Djulbegovic B: Colony-stimulating factors for chemotherapy-induced febrile neutropenia. Cochrane Database Syst Rev. 2014:CD0030392014.PubMed/NCBI
43	Qu N, Sun Y, Li Y, Hao F, Qiu P, Teng L, Xie J and Gao Y: Docetaxel-loaded human serum albumin (HSA) nanoparticles: Synthesis, characterization, and evaluation. Biomed Eng Online. 18:112019. View Article : Google Scholar : PubMed/NCBI
44	Huang J, Wu B, Zhou Z, Hu S, Xu H, Piao Y, Zheng H, Tang J, Liu X and Shen Y: Drug-binding albumins forming stabilized nanoparticles for efficient anticancer therapy. Nanomedicine. 21:1020582019. View Article : Google Scholar : PubMed/NCBI
45	Hawkins MJ, Soon-Shiong P and Desai N: Protein nanoparticles as drug carriers in clinical medicine. Adv Drug Deliv Rev. 60:876–885. 2008. View Article : Google Scholar : PubMed/NCBI