Skip to main content

Advertisement

SpringerLink
Log in

The utility of serum osteopontin levels for predicting postoperative complications after colorectal cancer surgery

  • Original Article
  • Published:
International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Background/Aim

Osteopontin (OPN) is a secretory glycoprotein, which is expressed not only in osteoblasts, but immune cells including macrophages and activated T cells. Its pleiotropic immune functions, such as bone remodeling, cancer progression, immune response, and inflammation have been reported previously. However, the association between OPN and postoperative complications (POC) after colorectal cancer (CRC) surgery has not been studied, so far.

Methods

Peripheral blood samples were collected before (pre) and immediately after surgery (post), and on postoperative days (POD) 1, 3, 5, and 7. Serum OPN levels were measured by ELISA. In total, 78 patients who underwent elective CRC surgery were divided into the No-POC (n = 54) and POC (n = 24) groups.

Results

The POC group had significantly higher OPN levels than the No-POC group throughout the postoperative observation period. The maximum OPN levels from pre- to postsurgical samples showed the best predictive potential for POCs (cut off: 20.75 ng/mL, area under the curve: 0.724) and were correlated with length of postoperative stays. OPN values were significantly correlated with C-reactive protein on POD3 and were identified as an independent predictive marker for POCs (odds ratio: 3.88, 95% CI: 1.175–12.798, P = 0.026). The severity of POCs was reflected in increased OPN levels.

Conclusion

Increased postoperative OPN was associated with increased postoperative inflammatory host responses and POC after CRC surgery. Serum OPN level may be a useful biomarker for early prediction of POC and it may provide additional information for treatment decisions to prevent POC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Arnold M, Sierra MS, Laversanne M et al (2017) Global patterns and trends in colorectal cancer incidence and mortality. Gut 66:683–691

    Article  PubMed  Google Scholar 

  2. Torre LA, Siegel RL, Ward EM et al (2016) Global cancer incidence and mortality rates and trends–an update. Cancer Epidemiol Biomarkers Prev 25:16–27

    Article  PubMed  Google Scholar 

  3. Oliphant R, Nicholson GA, Horgan PG et al (2014) The impact of surgical specialisation on survival following elective colon cancer surgery. Int J Colorectal Dis 29:1143–1150

    Article  PubMed  Google Scholar 

  4. Alves A, Panis Y, Mathieu P et al (2005) Postoperative mortality and morbidity in French patients undergoing colorectal surgery: results of a prospective multicenter study. Arch Surg 140:278–283 (discussion 284)

    Article  PubMed  Google Scholar 

  5. Maruyama H, Kusachi S, Makino H et al (2020) Postoperative infection after colorectal surgery: subanalysis of data from the 2015 Japan postoperative infectious complications survey. J Nippon Med Sch 87:204–210

    Article  PubMed  Google Scholar 

  6. McSorley ST, Watt DG, Horgan PG et al (2016) Postoperative systemic inflammatory response, complication severity, and survival following surgery for colorectal cancer. Ann Surg Oncol 23:2832–2840

    Article  PubMed  PubMed Central  Google Scholar 

  7. Law WL, Choi HK, Lee YM et al (2007) The impact of postoperative complications on long-term outcomes following curative resection for colorectal cancer. Ann Surg Oncol 14:2559–2566

    Article  PubMed  Google Scholar 

  8. Miyamoto Y, Hiyoshi Y, Tokunaga R et al (2020) Postoperative complications are associated with poor survival outcome after curative resection for colorectal cancer: a propensity-score analysis. J Surg Oncol 122:344–349

    Article  PubMed  Google Scholar 

  9. Wang KX, Denhardt DT (2008) Osteopontin: role in immune regulation and stress responses. Cytokine Growth Factor Rev 19:333–345

    Article  CAS  PubMed  Google Scholar 

  10. Cantor H, Shinohara ML (2009) Regulation of T-helper-cell lineage development by osteopontin: the inside story. Nat Rev Immunol 9:137–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lund SA, Giachelli CM, Scatena M (2009) The role of osteopontin in inflammatory processes. J Cell Commun Signal 3:311–322

    Article  PubMed  PubMed Central  Google Scholar 

  12. Santamaria MH, Corral RS (2013) Osteopontin-dependent regulation of Th1 and Th17 cytokine responses in Trypanosoma cruzi-infected C57BL/6 mice. Cytokine 61:491–498

    Article  CAS  PubMed  Google Scholar 

  13. Hirano Y, Aziz M, Yang WL et al (2015) Neutralization of osteopontin attenuates neutrophil migration in sepsis-induced acute lung injury. Crit Care 19:53

    Article  PubMed  PubMed Central  Google Scholar 

  14. Aziz MM, Ishihara S, Mishima Y et al (2009) MFG-E8 attenuates intestinal inflammation in murine experimental colitis by modulating osteopontin-dependent alphavbeta3 integrin signaling. J Immunol 182:7222–7232

    Article  CAS  PubMed  Google Scholar 

  15. Cen C, Aziz M, Yang WL et al (2017) Osteopontin blockade attenuates renal injury after ischemia reperfusion by inhibiting NK cell infiltration. Shock 47:52–60

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Dindo D, Demartines N, Clavien P-A (2004) Classification of surgical complications. Ann Surg 240:205–213

    Article  PubMed  PubMed Central  Google Scholar 

  17. Jain S, Chakraborty G, Bulbule A et al (2007) Osteopontin: an emerging therapeutic target for anticancer therapy. Expert Opin Ther Targets 11:81–90

    Article  CAS  PubMed  Google Scholar 

  18. Zhao H, Chen Q, Alam A et al (2018) The role of osteopontin in the progression of solid organ tumour. Cell Death Dis 9:356

    Article  PubMed  PubMed Central  Google Scholar 

  19. Hattori T, Iwasaki-Hozumi H, Bai G et al (2021) Both full-length and protease-cleaved products of osteopontin are elevated in infectious diseases. Biomedicines 9(8):1006

    Article  PubMed  PubMed Central  Google Scholar 

  20. Mishima R, Takeshima F, Sawai T et al (2007) High plasma osteopontin levels in patients with inflammatory bowel disease. J Clin Gastroenterol 41:167–172

    Article  CAS  PubMed  Google Scholar 

  21. Scatena M, Liaw L, Giachelli CM (2007) Osteopontin: a multifunctional molecule regulating chronic inflammation and vascular disease. Arterioscler Thromb Vasc Biol 27:2302–2309

    Article  CAS  PubMed  Google Scholar 

  22. Menger MD, Vollmar B (2004) Surgical trauma: hyperinflammation versus immunosuppression? Langenbecks Arch Surg 389:475–484

    Article  PubMed  Google Scholar 

  23. Roumen RM, Hendriks T, van der Ven-Jongekrijg J et al (1993) Cytokine patterns in patients after major vascular surgery, hemorrhagic shock, and severe blunt trauma. Relation with subsequent adult respiratory distress syndrome and multiple organ failure. Ann Surg 218:769–776

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Korner H, Nielsen HJ, Soreide JA et al (2009) Diagnostic accuracy of C-reactive protein for intraabdominal infections after colorectal resections. J Gastrointest Surg 13:1599–1606

    Article  PubMed  Google Scholar 

  25. Platt JJ, Ramanathan ML, Crosbie RA et al (2012) C-reactive protein as a predictor of postoperative infective complications after curative resection in patients with colorectal cancer. Ann Surg Oncol 19:4168–4177

    Article  PubMed  Google Scholar 

  26. Warschkow R, Tarantino I, Torzewski M et al (2011) Diagnostic accuracy of C-reactive protein and white blood cell counts in the early detection of inflammatory complications after open resection of colorectal cancer: a retrospective study of 1,187 patients. Int J Colorectal Dis 26:1405–1413

    Article  PubMed  Google Scholar 

  27. Cardinale F, Chinellato I, Caimmi S et al (2011) Perioperative period: immunological modifications. Int J Immunopathol Pharmacol 24:S3-12

    Article  CAS  PubMed  Google Scholar 

  28. Lenz A, Franklin GA, Cheadle WG (2007) Systemic inflammation after trauma. Injury 38:1336–1345

    Article  PubMed  Google Scholar 

  29. Zhang X, Tang M, Zhang Q et al (2021) The GLIM criteria as an effective tool for nutrition assessment and survival prediction in older adult cancer patients. Clin Nutr 40:1224–1232

    Article  PubMed  Google Scholar 

  30. van Kooten RT, Bahadoer RR, Peeters K et al (2021) Preoperative risk factors for major postoperative complications after complex gastrointestinal cancer surgery: a systematic review. Eur J Surg Oncol 47:3049–3058

    Article  PubMed  Google Scholar 

  31. van Kooten RT, Voeten DM, Steyerberg EW et al (2022) Patient-related prognostic factors for anastomotic leakage, major complications, and short-term mortality following esophagectomy for cancer: a systematic review and meta-analyses. Ann Surg Oncol 29:1358–1373

    Article  PubMed  Google Scholar 

  32. Morimoto J, Kon S, Matsui Y et al (2010) Osteopontin; as a target molecule for the treatment of inflammatory diseases. Curr Drug Targets 11:494–505

    Article  CAS  PubMed  Google Scholar 

  33. Shao Z, Morser J, Leung LLK (2014) Thrombin cleavage of osteopontin disrupts a pro-chemotactic sequence for dendritic cells, which is compensated by the release of its pro-chemotactic C-terminal fragment. J Biol Chem 289:27146–27158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Agnihotri R, Crawford HC, Haro H et al (2001) Osteopontin, a novel substrate for matrix metalloproteinase-3 (stromelysin-1) and matrix metalloproteinase-7 (matrilysin). J Biol Chem 276:28261–28267

    Article  CAS  PubMed  Google Scholar 

  35. Ashkar S, Weber GF, Panoutsakopoulou V et al (2000) Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity. Science 287:860–864

    Article  CAS  PubMed  Google Scholar 

  36. Chabas D, Baranzini SE, Mitchell D et al (2001) The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease. Science 294:1731–1735

    Article  CAS  PubMed  Google Scholar 

  37. Da Silva AP, Pollett A, Rittling SR et al (2006) Exacerbated tissue destruction in DSS-induced acute colitis of OPN-null mice is associated with downregulation of TNF-alpha expression and non-programmed cell death. J Cell Physiol 208:629–639

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (15K10037: Matsuda A). We thank James P. Mahaffey, PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

Author information

Authors and Affiliations

  1. Department of Surgery, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari , Inzai, Chiba, 270-1694, Japan

    Kumiko Sekiguchi, Akihisa Matsuda, Marina Yamada, Satoshi Matsumoto, Nobuyuki Sakurazawa, Youichi Kawano & Masao Miyashita

  2. Department of Surgery, Nippon Medical School Tama Nagayama Hospital, 1-7-1 Nagayama, Tama, Tokyo, 206-8512, Japan

    Kumiko Sekiguchi

  3. Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan

    Akihisa Matsuda, Nobuyuki Sakurazawa, Takeshi Yamada & Hiroshi Yoshida

  4. Faculty of Medical Science, Nippon Sport Science University, 1221-1 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa, 227-0033, Japan

    Marina Yamada

Authors
  1. Kumiko Sekiguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akihisa Matsuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marina Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Satoshi Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nobuyuki Sakurazawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Youichi Kawano
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Takeshi Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Masao Miyashita
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hiroshi Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

AM: Study concept and design; KS, MY, NS: Acquisition of data; AM, SM, YK, TY: Analysis and interpretation of data; KS, AM: Drafting of the manuscript; MM, HY: Study supervision.

Corresponding author

Correspondence to Akihisa Matsuda.

Ethics declarations

Conflict of interest

All authors have no conflict of interest to declare.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 18 kb)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sekiguchi, K., Matsuda, A., Yamada, M. et al. The utility of serum osteopontin levels for predicting postoperative complications after colorectal cancer surgery. Int J Clin Oncol 27, 1706–1716 (2022). https://doi.org/10.1007/s10147-022-02225-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10147-022-02225-6

Keywords

Search

Navigation