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23-09-2022 | Metastasis | Original Article

Detection, Role and Prognostic Value of Cancer-associated Fibroblasts in Colorectal Cancer

Authors: Nina Alexandrovna Oleynikova, I. A. Mikhailov, O. A. Kharlova, T. Yu. Zavidnyi, N. V. Danilova, P. G. Mal`kov

Published in: Indian Journal of Surgical Oncology | Issue 1/2023

Abstract

Cancer-associated fibroblasts (CAFs) — mesenchymal cells in the tumor stroma, play one of the leading roles in tumor progression in many different tumors, including colorectal cancer. Scientists have described many markers for CAFs, but none of them is specific. We performed immunohistochemistry tests using five antibodies (αSMA, POD, FAP, PDGFRα, PDGFRβ) to investigate CAFs in three zones of 49 colorectal adenocarcinomas: apical, central, and invasive edge. We revealed the reliable correlation between high PDGFRβ and PDGFRα value in the apical zone and deeper invasion (T3–T4) (p = 0.0281 and p = 0.0137). High αSMA level in apical zone (p = 0.0001), αSMA level in central zone (p = 0.019), POD level in apical zone (p = 0.0222), POD level in central zone (p = 0.0206) and PDGFRβ level in apical zone (p = 0.014) correlated reliably with the presence of metastasis in lymphatic nodules. For the first time, focused on the inner layer of CAF adjacent to tumor complexes. We observed that cases with inner αSMA expression were significantly more often (p = 0.023) characterized by the presence of regional lymph node metastasis compared with cases with mix of CAF markers (p = 0.007) and with cases with inner POD expression (p = 0.024). The found relationships between the level of markers and the presence of metastases indicate their clinical significance.

Kalluri R (2016) The biology and function of fibroblasts in cancer. Nat Rev Cancer 16(9):582–598. https://doi.org/10.1038/nrc.2016.73CrossRefPubMed

Koliaraki V, Prados A, Armaka M, Kollias G (2020) The mesenchymal context in inflammation, immunity and cancer. Nat Immunol 21(9):974–982. https://doi.org/10.1038/s41590-020-0741-2CrossRefPubMed

Biffi G, Tuveson DA (2021) Diversity and biology of cancer-associated fibroblasts. Physiol Rev 101(1):147–176. https://doi.org/10.1152/physrev.00048.2019CrossRefPubMed

Berdiel-Acer M, Sanz-Pamplona R, Calon A et al (2014) Differences between CAFs and their paired NCF from adjacent colonic mucosa reveal functional heterogeneity of CAFs, providing prognostic information. Mol Oncol 8(7):1290–1305. https://doi.org/10.1016/j.molonc.2014.04.006CrossRefPubMedPubMedCentral

Nishishita R, Morohashi S, Seino H et al (2018) Expression of cancer-associated fibroblast markers in advanced colorectal cancer. Oncol Lett 15(5):6195–6202. https://doi.org/10.3892/ol.2018.8097CrossRefPubMedPubMedCentral

Sandberg TP, Stuart M, Oosting J et al (2019) Increased expression of cancer-associated fibroblast markers at the invasive front and its association with tumor-stroma ratio in colorectal cancer. BMC Cancer 19(1):284. https://doi.org/10.1186/s12885-019-5462-2CrossRefPubMedPubMedCentral

Dumont N, Liu B, Defilippis RA et al (2013) Breast fibroblasts modulate early dissemination, tumorigenesis, and metastasis through alteration of extracellular matrix characteristics. Neoplasia 15(3):249–262. https://doi.org/10.1593/neo.121950CrossRefPubMedPubMedCentral

Ishii G, Ochiai A, Neri S (2016) Phenotypic and functional heterogeneity of cancer-associated fibroblast within the tumor microenvironment. Adv Drug Deliv Rev 99(Pt B):186–196. https://doi.org/10.1016/j.addr.2015.07.007CrossRefPubMed

Ozdemir BC, Pentcheva-Hoang T, Carstens JL et al (2014) Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival. Cancer Cell 25(6):719–734. https://doi.org/10.1016/j.ccr.2014.04.005CrossRefPubMedPubMedCentral

10.

WHO Classification of Tumors (2019) Digestive system tumors, 5th edn. WHO Press, Switzerland

11.

Oleynikova N, Malkov P, Danilova N. (2020). Changes in the classification of malignant colon epithelial neoplasms. (WHO, 2019, 5th edition). Arkhiv Patologii 82(3), 38–46. https://doi.org/10.17116/patol20208203138

12.

Oe S, Hasegawa K, Nagase S et al (2010) Expression of podoplanin in epithelial ovarian carcinomas and its potential as a marker for clear cell adenocarcinoma. Int J Gynecol Pathol  Off J Int Soc Gynecol Pathol 29(5):405–410. https://doi.org/10.1097/PGP.0b013e3181d3261eCrossRefPubMed

13.

Kubouchi Y, Yurugi Y, Wakahara M et al (2018) Podoplanin expression in cancer-associated fibroblasts predicts unfavourable prognosis in patients with pathological stage IA lung adenocarcinoma. Histopathology 72(3):490–499. https://doi.org/10.1111/his.13390CrossRefPubMed

14.

Yamanashi T, Nakanishi Y, Fujii G et al (2009) Podoplanin expression identified in stromal fibroblasts as a favorable prognostic marker in patients with colorectal carcinoma. Oncology 77(1):53–62. https://doi.org/10.1159/000226112CrossRefPubMed

15.

Choi SY, Sung R, Lee SJ et al (2013) Podoplanin, alpha-smooth muscle actin or S100A4 expressing cancer-associated fibroblasts are associated with different prognosis in colorectal cancers. J Korean Med Sci 28(9):1293–1301. https://doi.org/10.3346/jkms.2013.28.9.1293CrossRefPubMedPubMedCentral

16.

Kilvaer TK, Rakaee M, Hellevik T et al (2019) Differential prognostic impact of platelet-derived growth factor receptor expression in NSCLC. Sci Rep 9(1):10163. https://doi.org/10.1038/s41598-019-46510-3CrossRefPubMedPubMedCentral

Title: Detection, Role and Prognostic Value of Cancer-associated Fibroblasts in Colorectal Cancer
Authors: Nina Alexandrovna Oleynikova
I. A. Mikhailov
O. A. Kharlova
T. Yu. Zavidnyi
N. V. Danilova
P. G. Mal`kov
Publication date: 23-09-2022
Publisher: Springer India
Keywords: Metastasis
Colorectal Cancer
Colorectal Cancer
Published in: Indian Journal of Surgical Oncology / Issue 1/2023
Print ISSN: 0975-7651
Electronic ISSN: 0976-6952
DOI: https://doi.org/10.1007/s13193-022-01653-0

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Detection, Role and Prognostic Value of Cancer-associated Fibroblasts in Colorectal Cancer

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