High Co-expression of Large Tenascin C Splice Variants in Stromal Tissue and Annexin A2 in Cancer Cell Membranes is Associated with Poor Prognosis in Pancreatic Cancer
- 28.08.2019
- Translational Research and Biomarkers
Erschienen in:
- Verfasst von
- Kei Hagiwara, MD
- Norifumi Harimoto, MD, PhD
- Takehiko Yokobori, MD
- Ryo Muranushi, MD
- Kouki Hoshino, MD
- Dorgormaa Gantumur, MD
- Takahiro Yamanaka, MD
- Norihiro Ishii, MD
- Mariko Tsukagoshi, MD
- Takamichi Igarashi, MD
- Hiroshi Tanaka, MD
- Akira Watanabe, MD
- Norio Kubo, MD
- Kenichiro Araki, MD
- Yasuo Hosouchi, MD
- Ken Shirabe, MD
- Erschienen in
- Annals of Surgical Oncology | Ausgabe 3/2020
Abstract
Background
Pancreatic cancer tissue contains abundant stromal components, including extracellular matrix proteins such as tenascin C (TNC), which exists as large (TNC-L) and non-large splice variants. Here, we examined human pancreatic cancer specimens for the expression of total TNC (TNC-ALL) and TNC-L in the stroma and annexin A2 (ANXA2), a cell surface receptor for TNC, and evaluated their significance as prognostic markers for pancreatic cancer.
Methods
Expression of ANXA2, TNC-ALL, and TNC-L was examined in 106 pancreatic cancer tissues from patients who underwent curative resection and who had not received prior therapy or surgery. Protein expression was measured by immunohistochemistry and scored on a semi-quantitative scale. The relationships between protein expression, clinicopathological factors, and prognosis were evaluated by Cox proportional hazards analysis.
Results
TNC-ALL and TNC-L were detected mainly in the stroma, whereas ANXA2 was predominantly expressed in cancer cell membranes. TNC-ALL was also expressed in non-tumor pancreatic tissue. High levels of stromal TNC-L and membranous ANXA2, but not stromal TNC-ALL, were independently associated with cancer progression and poor prognosis. Moreover, high co-expression of stromal TNC-L and membranous ANXA2 was a superior indicator of poor prognosis compared with detection of TNC-ALL, TNC-L, or ANXA2 alone.
Conclusions
Our data suggest that co-expression of stromal TNC-L and membranous ANXA2 is a poor prognostic marker compared with detection of TNC-L or ANXA2 alone for pancreatic cancer patients. Additionally, targeting of crosstalk between stromal TNC and cancer cell ANXA2 could be a promising therapeutic strategy to overcome refractory pancreatic cancer.
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- Titel
- High Co-expression of Large Tenascin C Splice Variants in Stromal Tissue and Annexin A2 in Cancer Cell Membranes is Associated with Poor Prognosis in Pancreatic Cancer
- Verfasst von
-
Kei Hagiwara, MD
Norifumi Harimoto, MD, PhD
Takehiko Yokobori, MD
Ryo Muranushi, MD
Kouki Hoshino, MD
Dorgormaa Gantumur, MD
Takahiro Yamanaka, MD
Norihiro Ishii, MD
Mariko Tsukagoshi, MD
Takamichi Igarashi, MD
Hiroshi Tanaka, MD
Akira Watanabe, MD
Norio Kubo, MD
Kenichiro Araki, MD
Yasuo Hosouchi, MD
Ken Shirabe, MD
- Publikationsdatum
- 28.08.2019
- Verlag
- Springer International Publishing
- Erschienen in
-
Annals of Surgical Oncology / Ausgabe 3/2020
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681 - DOI
- https://doi.org/10.1245/s10434-019-07708-x
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