Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ASCO Annual Meeting 2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

2024 ASCO Annual Meeting

Keep up to date with all the top stories and latest evidence with our hub page, including official congress videos and expert takeaways.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Underweight | Research

S100A8, S100A9 and S100A8/A9 heterodimer as novel cachexigenic factors for pancreatic cancer-induced cachexia

Authors: Wei-Chih Liao, Chih-Ta Chen, You-Shu Tsai, Xin-Ya Wang, Yen-Tzu Chang, Ming-Shiang Wu, Lu-Ping Chow

Published in: BMC Cancer | Issue 1/2023

Login to get access

Abstract

Background

Cancer cachexia, occurring in ~ 80% pancreatic cancer (PC) patients overall, is a paraneoplastic syndrome mediated by cancer-induced systemic inflammation and characterized by weight loss and skeletal muscle wasting. Identifying clinically relevant PC-derived pro-inflammatory factors with cachexigenic potential may provide novel insights and therapeutic strategies.

Methods

Pro-inflammatory factors with cachexigenic potential in PC were identified by bioinformatic analysis. The abilities of selected candidate factors in inducing skeletal muscle atrophy were investigated. Expression levels of candidate factors in tumors and sera was compared between PC patients with and without cachexia. Associations between serum levels of the candidates and weight loss were assessed in PC patients.

Results

S100A8, S100A9, and S100A8/A9 were identified and shown to induce C2C12 myotube atrophy. Tumors of PC patients with cachexia had markedly elevated expression of S100A8 (P = 0.003) and S100A9 (P < 0.001). PC patients with cachexia had significantly higher serum levels of S100A8, S100A9 and S100A8/A9. Serum levels of these factors positively correlated with percentage of weight loss [correlation coefficient: S100A8: 0.33 (P < 0.001); S100A9: 0.30 (P < 0.001); S100A8/A9: 0.24 (P = 0.004)] and independently predicted the occurrence of cachexia [adjusted odds ratio (95% confidence interval) per 1ng/ml increase: S100A8 1.11 (1.02–1.21), P = 0.014; S100A9 1.10 (1.04–1.16), P = 0.001; per 1 µg/ml increase: S100A8/A9 1.04 (1.01–1.06), P = 0.009].

Conclusions

Atrophic effects of S100A8, S100A9, and S100A8/A9 indicated them as potential pathogenic factors of PC-induced cachexia. In addition, the correlation with the degree of weight loss and prediction of cachexia in PC patients implicated their potential utility in the diagnosis of PC-induced cachexia.
Appendix
Available only for authorised users
Literature
1.
Park W, Chawla A, O’Reilly EM. Pancreatic cancer: a review. Jama-J Am Med Assoc. 2021;326(20):2081.
2.
Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting Cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74(11):2913–21.CrossRefPubMed
3.
4.
Bachmann J, Ketterer K, Marsch C, et al. Pancreatic cancer related cachexia: influence on metabolism and correlation to weight loss and pulmonary function. BMC Cancer. 2009;9:255.CrossRefPubMedPubMedCentral
5.
Bachmann J, Heiligensetzer M, Krakowski-Roosen H, Buchler MW, Friess H, Martignoni ME. Cachexia worsens prognosis in patients with resectable pancreatic cancer. J Gastrointest Surg. 2008;12(7):1193–201.CrossRefPubMed
6.
Porporato PE. Understanding cachexia as a cancer metabolism syndrome. Oncogenesis. 2016;5.
7.
Argiles JM, Busquets S, Stemmler B, Lopez-Soriano FJ. Cancer cachexia: understanding the molecular basis. Nat Rev Cancer. 2014;14(11):754–62.CrossRefPubMed
8.
Mayers JR, Wu C, Clish CB, et al. Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development. Nat Med. 2014;20(10):1193–8.CrossRefPubMedPubMedCentral
9.
Martin L, Birdsell L, MacDonald N, et al. Cancer Cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, Independent of Body Mass Index. J Clin Oncol. 2013;31(12):1539–47.CrossRefPubMed
10.
Fujiwara Y, Kobayashi T, Chayahara N et al. Metabolomics evaluation of serum markers for Cachexia and their intra- day variation in patients with Advanced Pancreatic Cancer. PLoS ONE. 2014;9(11).
11.
Bye A, Wesseltoft-Rao N, Iversen PO et al. Alterations in inflammatory biomarkers and energy intake in cancer cachexia: a prospective study in patients with inoperable pancreatic cancer. Med Oncol. 2016;33(6).
12.
Garcia JM, Garcia-Touza M, Hijazi RA, et al. Active ghrelin levels and active to total ghrelin ratio in cancer-induced cachexia. J Clin Endocr Metab. 2005;90(5):2920–6.CrossRefPubMed
13.
Talbert EE, Lewis HL, Farren MR, et al. Circulating monocyte chemoattractant protein-1 (MCP-1) is associated with cachexia in treatment-naive pancreatic cancer patients. J Cachexia Sarcopeni. 2018;9(2):358–68.CrossRef
14.
15.
Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45(W1):W98–W102.CrossRefPubMedPubMedCentral
16.
Liao WC, Huang BS, Yu YH, et al. Galectin-3 and S100A9: novel diabetogenic factors mediating pancreatic Cancer-Associated Diabetes. Diabetes Care. 2019;42(9):1752–9.CrossRefPubMed
17.
Chen CT, Liao LZ, Lu CH, et al. Quantitative phosphoproteomic analysis identifies the potential therapeutic target EphA2 for overcoming sorafenib resistance in hepatocellular carcinoma cells. Exp Mol Med. 2020;52(3):497–513.CrossRefPubMedPubMedCentral
18.
Amin MB, American Joint Committee on Cancer.,American Cancer Society., AJCC cancer staging manual. Eight edition / editor-in-chief, Mahul B. Amin, MD, FCAP; editors, Stephen B. Edge, MD, FACS and 16 others ; Donna M. Gress, RHIT, CTR - Technical editor ; Laura R. Meyer, CAPM - Managing editor. ed. 2017, Chicago IL: American Joint Committee on Cancer, Springer. xvii, 1024 pages.
19.
Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis–2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62(1):102–11.CrossRefPubMed
20.
Schneider A, Lohr JM, Singer MV. The M-ANNHEIM classification of chronic pancreatitis: introduction of a unifying classification system based on a review of previous classifications of the disease. J Gastroenterol. 2007;42(2):101–19.CrossRefPubMed
21.
Tseng PH, Hung CS, Tu CH, et al. Association of incidence of acid-related Upper Gastrointestinal Disorders with Glycated Hemoglobin Level. J Clin Endocrinol Metab. 2022;107(6):e2563–e71.CrossRefPubMed
22.
Kim EH, Kim KW, Shin Y, et al. Reference data and T-Scores of lumbar skeletal muscle area and its skeletal muscle indices measured by CT scan in a healthy korean Population. J Gerontol a-Biol. 2021;76(2):265–71.CrossRef
23.
Pruenster M, Vogl T, Roth J, Sperandio M. S100A8/A9: from basic science to clinical application. Pharmacol Therapeut. 2016;167:120–31.CrossRef
24.
Neus Martinez-Bosch LEB, Carlos A, Orozco M, Moreno L, Visa M, Iglesias L, Oldfield JP, Neoptolemos. William Greenhalf, Julie Earl, Alfredo Carrato, Eithne Costello and Pilar Navarro. Increased plasma levels of galectin-1 in pancreatic cancer: potential use as biomarker. Oncotarget. 2018;9(68):32984–96.CrossRefPubMedPubMedCentral
25.
Sun Q, Zhang Y, Liu M, et al. Prognostic and diagnostic significance of galectins in pancreatic cancer: a systematic review and meta-analysis. Cancer Cell Int. 2019;19:309.CrossRefPubMedPubMedCentral
26.
Padoan A, Plebani M, Basso D. Inflammation and pancreatic Cancer: focus on metabolism, Cytokines, and immunity. Int J Mol Sci. 2019;20(3).
27.
Samonig L, Loipetzberger A, Blochl C et al. Proteins and molecular Pathways relevant for the Malignant Properties of Tumor-Initiating Pancreatic Cancer cells. Cells. 2020;9(6).
28.
Shen JJ, Person MD, Zhu JJ, Abbruzzese JL, Li DH. Protein expression profiles in pancreatic adenocarcinoma compared with normal pancreatic tissue and tissue affected by pancreatitis as detected by two-dimensional gel electrophoresis and mass spectrometry. Cancer Res. 2004;64(24):9018–26.CrossRefPubMed
29.
Kung PJ, Lai TY, Cao J, et al. The role of S100A9 in the interaction between pancreatic ductal adenocarcinoma cells and stromal cells. Cancer Immunol Immun. 2022;71(3):705–18.CrossRef
30.
Nedjadi T, Evans A, Sheikh A et al. S100A8 and S100A9 proteins form part of a paracrine feedback loop between pancreatic cancer cells and monocytes. BMC Cancer. 2018;18.
31.
Paval DR, Patton R, McDonald J, et al. A systematic review examining the relationship between cytokines and cachexia in incurable cancer. J Cachexia Sarcopenia Muscle. 2022;13(2):824–38.CrossRefPubMedPubMedCentral
32.
Bilir C, Engin H, Can M, Temi YB, Demirtas D. The prognostic role of inflammation and hormones in patients with metastatic cancer with cachexia. Med Oncol. 2015;32(3).
33.
Kemik O, Sumer A, Kemik AS et al. The relationship among acute-phase response proteins, cytokines and hormones in cachectic patients with colon cancer. World J Surg Oncol. 2010;8.
34.
Sharma A, Kandlakunta H, Nagpal SJS, et al. Model to determine risk of pancreatic Cancer in patients with New-Onset diabetes. Gastroenterology. 2018;155(3):730–9. e3.CrossRefPubMed
35.
Liao WC, Chen PR, Huang CC, et al. Relationship between pancreatic cancer-associated diabetes and cachexia. J Cachexia Sarcopeni. 2020;11(4):899–908.CrossRef
Metadata
Title
S100A8, S100A9 and S100A8/A9 heterodimer as novel cachexigenic factors for pancreatic cancer-induced cachexia
Authors
Wei-Chih Liao
Chih-Ta Chen
You-Shu Tsai
Xin-Ya Wang
Yen-Tzu Chang
Ming-Shiang Wu
Lu-Ping Chow
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-11009-8

Other articles of this Issue 1/2023

BMC Cancer 1/2023 Go to the issue

Research

Immunoglobulin superfamily 6 is a molecule involved in the anti-tumor activity of macrophages in lung adenocarcinoma

Research

Preoperative assessment of peripheral vascular invasion of pancreatic ductal adenocarcinoma based on high-resolution MRI

Research

TUBA1C: a new potential target of LncRNA EGFR-AS1 promotes gastric cancer progression

Research

Survival differences between patients with de novo and relapsed/progressed advanced non-small cell lung cancer without epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements

Research

Risk stratification and prognostic value of multi-modal MRI-based radiomics for extranodal nasal-type NK/T-cell lymphoma

Research

Developing a nomogram for preoperative prediction of cervical cancer lymph node metastasis by multiplex immunofluorescence
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

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
Image Credits