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Periostin as a key molecule defining desmoplastic environment in colorectal cancer

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Abstract

Categorizing desmoplastic reaction (DR) based on the histological findings of cancer-associated fibroblasts is shown to be a promising novel method to predict prognosis of patients with colorectal cancer (CRC). Periostin (POSTN) in cancer-associated stroma is reportedly associated with poor clinical outcomes. Immunohistochemical staining with an anti-POSTN antibody was performed in 73 patients with pStage III CRC (cohort 1). In addition, to evaluate mRNA and protein expression levels of POSTN, we analyzed paired normal and invasive cancer frozen specimens by quantitative real-time polymerase chain reaction and western blot analysis in 41 patients (cohort 2). In cohort 1, according to the DR categorization, 18, 22, and 33 patients were classified as immature, intermediate, and mature, respectively. High immunoreactivity of POSTN was observed 100%, 68.2%, and 27.3%, respectively (p < 0.0001). The 5-year relapse-free survival rates were 56.8% and 82.7% in high and low POSTN expression subgroups, respectively (p = 0.015). In cohort 2, the POSTN mRNA and protein levels were significantly higher in the immature stroma as compared to the stroma characterized as other DR patterns. POSTN expression was closely associated with DR categorization. POSTN may be a key molecule that contributes to the malignant potential of CRC.

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References

  1. McAllister SS, Weinberg RA (2010) Tumor-host interactions: a far-reaching relationship. J Clin Oncol 28:4022–4028

    Article  Google Scholar 

  2. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    Article  CAS  Google Scholar 

  3. Allen M, Louise JJ (2011) Jekyll and Hyde: the role of the microenvironment on the progression of cancer. J Pathol 223:162–176

    CAS  PubMed  Google Scholar 

  4. Joyce JA, Pollard JW (2009) Microenvironmental regulation of metastasis. Nat Rev Cancer 9:239–252

    Article  CAS  Google Scholar 

  5. Ueno H, Jones A, Jass JR, Talbot IC (2002) Clinicopathological significance of the ‘keloid-like’ collagen and myxoid stroma in advanced rectal cancer. Histopathology 40:327–334

    Article  CAS  Google Scholar 

  6. Ueno H, Jones AM, Wilkinson KH, Jass JR, Talbot IC (2004) Histological categorisation of fibrotic cancer stroma in advanced rectal cancer. Gut 53:581–586

    Article  CAS  Google Scholar 

  7. Ueno H, Shinto E, Shimazaki H, Kajiwara Y, Sueyama T, Yamamoto J, Hase K (2015) Histologic categorization of desmoplastic reaction: its relevance to the colorectal cancer microenvironment and prognosis. Ann Surg Oncol 22:1504–1512

    Article  Google Scholar 

  8. Ueno H, Kanemitsu Y, Sekine S, Ishiguro M, Ito E, Hashiguchi Y, Kondo F, Shimazaki H, Mochizuki S, Kajiwara Y, Shinto E, Yamamoto J (2017) Desmoplastic pattern at the tumor front defines poor-prognosis subtypes of colorectal cancer. Am J Surg Pathol 41:1506–1512

    Article  Google Scholar 

  9. Ueno H, Sekine S, Oshiro T, Kanemitsu Y, Hamaguchi T, Shida D, Takashima A, Ishiguro M, Ito E, Hashiguchi Y, Kondo F, Shimazaki H, Mochizuki S, Kajiwara Y, Shinto E, Yamamoto J, Shimada Y (2018) Disentangling the prognostic heterogeneity of stage III colorectal cancer through histologic stromal categorization. Surgery 163:777–783

    Article  Google Scholar 

  10. Horiuchi K, Amizuka N, Takeshita S, Takamatsu H, Katsuura M, Ozawa H, Toyama Y, Bonewald LF, Kudo A (1999) Identification and characterization of a novel protein, periostin, with restricted expression to periosteum and periodontal ligament and increased expression by transforming growth factor beta. J Bone Miner Res 14:1239–1249

    Article  CAS  Google Scholar 

  11. Morra L, Moch H (2011) Periostin expression and epithelial-mesenchymal transition in cancer: a review and an update. Virchows Arch 459:465–475

    Article  CAS  Google Scholar 

  12. Conway SJ, Izuhara K, Kudo Y, Litvin J, Markwald R, Ouyang G, Arron JR, Holweg CTJ, Kudo A (2014) The role of periostin in tissue remodeling across health and disease. Cell Mol Life Sci 71:1279–1288

    Article  CAS  Google Scholar 

  13. Ben QW, ** XL, Liu J, Cai X, Yuan F, Yuan YZ (2011) Periostin, a matrix specific protein, is associated with proliferation and invasion of pancreatic cancer. Oncol Rep 25:709–716

    CAS  PubMed  Google Scholar 

  14. Erkan M, Kleeff J, Gorbachevski A, Reiser C, Mitkus T, Esposito I, Giese T, Büchler MW, Giese NA, Friess H (2007) Periostin creates a tumor-supportive microenvironment in the pancreas by sustaining fibrogenic stellate cell activity. Gastroenterology 132:1447–1464

    Article  CAS  Google Scholar 

  15. Ryner L, Guan Y, Firestein R, **ao Y, Choi Y, Rabe C, Lu S, Fuentes E, Huw LY, Lackner MR, Fu L, Amler LC, Bais C, Wang Y (2015) Upregulation of periostin and reactive stroma is associated with primary chemoresistance and predicts clinical outcomes in epithelial ovarian cancer. Clin Cancer Res 21:2941–2951

    Article  CAS  Google Scholar 

  16. Tian Y, Choi CH, Li QK, Rahmatpanah FB, Chen X, Kim SR, Veltri R, Chia D, Zhang Z, Mercola D, Zhang H (2015) Overexpression of periostin in stroma positively associated with aggressive prostate cancer. PLoS One 10:e0121502

    Article  Google Scholar 

  17. Underwood TJ, Hayden AL, Derouet M, Garcia E, Noble F, White MJ, Thirdborough S, Mead A, Clemons N, Mellone M, Uzoho C, Primrose JN, Blaydes JP, Thomas GJ (2015) Cancer-associated fibroblasts predict poor outcome and promote periostin-dependent invasion in oesophageal adenocarcinoma. J Pathol 235:466–477

    Article  CAS  Google Scholar 

  18. Kikuchi Y, Kunita A, Iwata C, Komura D, Nishiyama T, Shimazu K, Takeshita K, Shibahara J, Kii I, Morishita Y, Yashiro M, Hirakawa K, Miyazono K, Kudo A, Fukayama M, Kashima TG (2014) The niche component periostin is produced by cancer-associated fibroblasts, supporting growth of gastric cancer through ERK activation. Am J Pathol 184:859–870

    Article  CAS  Google Scholar 

  19. Nuzzo PV, Rubagotti A, Zinoli L, Salvi S, Boccardo S, Boccardo F (2016) The prognostic value of stromal and epithelial periostin expression in human breast cancer: correlation with clinical pathological features and mortality outcome. BMC Cancer 16:95

    Article  CAS  Google Scholar 

  20. Kim GE, Lee JS, Park MH, Yoon JH (2017) Epithelial periostin expression is correlated with poor survival in patients with invasive breast carcinoma. PLoS One 12:e0187635

    Article  Google Scholar 

  21. Utispan K, Thuwajit P, Abiko Y, Charngkaew K, Paupairoj A, Chau-in S, Thuwajit C (2010) Gene expression profiling of cholangiocarcinoma-derived fibroblast reveals alterations related to tumor progression and indicates periostin as a poor prognostic marker. Mol Cancer 9:13

    Article  Google Scholar 

  22. Chang W, Gao X, Han Y, du Y, Liu Q, Wang L, Tan X, Zhang Q, Liu Y, Zhu Y, Yu Y, Fan X, Zhang H, Zhou W, Wang J, Fu C, Cao G (2014) Gene expression profiling-derived immunohistochemistry signature with high prognostic value in colorectal carcinoma. Gut 63:1457–1467

    Article  CAS  Google Scholar 

  23. Xu X, Chang W, Yuan J, Han X, Tan X, Ding Y, Luo Y, Cai H, Liu Y, Gao X, Liu Q, Yu Y, du Y, Wang H, Ma L, Wang J, Chen K, Ding Y, Fu C, Cao G (2016) Periostin expression in intra-tumoral stromal cells is prognostic and predictive for colorectal carcinoma via creating a cancer-supportive niche. Oncotarget 7:798–813

    Article  Google Scholar 

  24. Oh HJ, Bae JM, Wen XY, Cho NY, Kim JH, Kang GH (2017) Overexpression of POSTN in tumor stroma is a poor prognostic indicator of colorectal cancer. J Pathol Transl Med 51:306–313

    Article  Google Scholar 

  25. Kajiwara Y, Ueno H, Hashiguchi Y, Shinto E, Shimazaki H, Mochizuki H, Hase K (2011) Expression of l1 cell adhesion molecule and morphologic features at the invasive front of colorectal cancer. Am J Clin Pathol 136:138–144

    Article  CAS  Google Scholar 

  26. Thiery JP (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2:442–454

    Article  CAS  Google Scholar 

  27. Tai IT, Dai M, Chen LB (2005) Periostin induction in tumor cell line explants and inhibition of in vitro cell growth by anti-periostin antibodies. Carcinogenesis 26:908–915

    Article  CAS  Google Scholar 

  28. Moniuszko T, Wincewicz A, Koda M, Domysławska I, Sulkowski S (2016) Role of periostin in esophageal, gastric and colon cancer. Oncol Lett 12:783–787

    Article  CAS  Google Scholar 

  29. Bao S, Ouyang G, Bai X, Huang Z, Ma C, Liu M, Shao R, Anderson RM, Rich JN, Wang XF (2004) Periostin potently promotes metastatic growth of colon cancer by augmenting cell survival via the Akt/PKB pathway. Cancer Cell 5:329–339

    Article  CAS  Google Scholar 

  30. Mesker WE, Junggeburt JM, Szuhai K et al (2007) The carcinoma-stromal ratio of colon carcinoma is an independent factor for survival compared to lymph node status and tumor stage. Cell Oncol 29:387–398

    PubMed  PubMed Central  Google Scholar 

  31. West NP, Dattani M, McShane P, Hutchins G, Grabsch J, Mueller W, Treanor D, Quirke P, Grabsch H (2010) The proportion of tumour cells is an independent predictor for survival in colorectal cancer patients. Br J Cancer 102:1519–1523

    Article  CAS  Google Scholar 

  32. Zippi M, De Toma G, Minervini G et al (2017) Desmoplasia influenced recurrence of disease and mortality in stage III colorectal cancer within five years after surgery and adjuvant therapy. Saudi J Gastroenterol 23:39–44

    Article  Google Scholar 

  33. Ueno H, Konishi T, Ishikawa Y, Shimazaki H, Ueno M, Aosasa S, Saiura A, Hase K, Yamamoto J (2014) Histologic categorization of fibrotic cancer stroma in the primary tumor is an independent prognostic index in resectable colorectal liver metastasis. Am J Surg Pathol 38:1380–1386

    Article  Google Scholar 

  34. Ueno H, Shinto E, Hashiguchi Y, Shimazaki H, Kajiwara Y, Sueyama T, Yamamoto J, Hase K (2015) In rectal cancer, the type of desmoplastic response after preoperative chemoradiotherapy is associated with prognosis. Virchows Arch 466:655–663

    Article  CAS  Google Scholar 

  35. Nearchou IP, Kajiwara Y, Mochizuki S, Harrison DJ, Caie PD, Ueno H (2019) Novel internationally verified method reports desmoplastic reaction as the most significant prognostic feature for disease-specific survival in stage II colorectal cancer. Am J Surg Pathol 43:1239–1248

    Article  Google Scholar 

  36. Norris RA, Damon B, Mironov V, Kasyanov V, Ramamurthi A, Moreno-Rodriguez R, Trusk T, Potts JD, Goodwin RL, Davis J, Hoffman S, Wen X, Sugi Y, Kern CB, Mjaatvedt CH, Turner DK, Oka T, Conway SJ, Molkentin JD, Forgacs G, Markwald RR (2007) Periostin regulates collagen fibrillogenesis and the biomechanical properties of connective tissues. J Cell Biochem 101:695–711

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, National Defense Medical College, 3-2, Namiki, Tokorozawa, Saitama, 359-8513, Japan

    Takahiro Sueyama, Yoshiki Kajiwara, Satsuki Mochizuki, Eiji Shinto, Kazuo Hase & Hideki Ueno

  2. Department of Laboratory Medicine, National Defense Medical College, Tokorozawa, Japan

    Hideyuki Shimazaki

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  1. Takahiro Sueyama
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  2. Yoshiki Kajiwara
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  3. Satsuki Mochizuki
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  4. Hideyuki Shimazaki
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  5. Eiji Shinto
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  6. Kazuo Hase
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  7. Hideki Ueno
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Contributions

Takahiro Sueyama: conceptualization, methodology, data analysis, investigation, visualization, and writing, and approval of the article.

Yoshiki Kajiwara, MD, PhD, Department of Surgery, National Defense Medical College, 3-2, Namiki, Tokorozawa: conceptualization, methodology, data analysis, visualization, and writing, and approval of the article.

Satsuki Mochizuki, PhD, Department of Surgery, National Defense Medical College, 3-2, Namiki, Tokorozawa: conceptualization, methodology, data analysis, investigation, visualization, and writing, and approval of the article.

Hideyuki Shimazaki: conceptualization, methodology, and writing, and approval of the article.

Eiji Shinto: conceptualization and writing and approval of the article.

Kazuo Hase: conceptualization, supervision, and writing, and approval of the article.

Hideki Ueno: conceptualization, supervision, project administration, and writing, and approval of the article. All authors gave final approval of the article.

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Correspondence to Yoshiki Kajiwara.

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Sueyama, T., Kajiwara, Y., Mochizuki, S. et al. Periostin as a key molecule defining desmoplastic environment in colorectal cancer. Virchows Arch 478, 865–874 (2021). https://doi.org/10.1007/s00428-020-02965-8

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  • DOI: https://doi.org/10.1007/s00428-020-02965-8

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