Cancer-associated fibroblasts correlate with poor prognosis in rectal cancer after chemoradiotherapy

  • Authors:
    • Susumu Saigusa
    • Yuji Toiyama
    • Koji Tanaka
    • Takeshi Yokoe
    • Yoshinaga Okugawa
    • Hiroyuki Fujikawa
    • Kohei Matsusita
    • Mikio Kawamura
    • Yasuhiro Inoue
    • Chikao Miki
    • Masato Kusunoki
  • View Affiliations

  • Published online on: Friday, January 14, 2011
  • Pages: 655-663 DOI: 10.3892/ijo.2011.906

Abstract

Cancer-associated fibroblasts (CAFs) in the stroma play an important role in influencing the proliferation, invasion and metastasis of cancer cells. Fibroblast activation protein-α (FAP-α) is known as a marker of CAFs, while stromal cell-derived factor-1 (SDF-1) is primarily expressed by CAFs. Herein, we investigated whether the expression levels of these genes are associated with clinical outcome after pre-operative chemoradiotherapy (CRT) in rectal cancer patients. We obtained total RNA from residual cancer stroma using microdissection from a total of 52 rectal cancer specimens from patients who underwent pre-operative CRT, we performed transcriptional analyses, and the serum protein concentrations in 40 matched microdissected specimens were measured by enzyme-linked immunosorbent assay. Additionally, we sought to clarify the location of FAP-α and SDF-1 expression using immunohistochemical staining. Of the 52 patients, 15.6 and 36.8% showed detectable FAP-α and SDF-1 mRNA expression, respectively. A significant correlation was observed between stromal FAP-α and SDF-1 mRNA levels. Moreover, there was a significant correlation between stromal SDF-1 gene expression levels and serum protein levels. Patients who developed distant recurrences after CRT had positive expression of both genes (P<0.05). The positive expression of both genes was also associated with poor probability of recurrence-free and overall survival (P<0.05). Patients with elevated serum SDF-1 levels had equally poor overall survival as those with positive stromal SDF-1 gene expression (P<0.05). In immunohistochemistry, both FAP-α and SDF-1 expression was observed in certain activated fibroblasts. In conclusion, FAP-α and SDF-1 expression was shown to be involved in tumor re-growth and recurrence in rectal cancer patients treated with pre-operative CRT.
Journal Cover

March 2011
Volume 38 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

2014 Impact Factor: 3.025
Ranked #30/211 Oncology
(total number of cites)

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APA
Saigusa, S., Toiyama, Y., Tanaka, K., Yokoe, T., Okugawa, Y., Fujikawa, H. ... Kusunoki, M. (2011). Cancer-associated fibroblasts correlate with poor prognosis in rectal cancer after chemoradiotherapy. International Journal of Oncology, 38, 655-663. http://dx.doi.org/10.3892/ijo.2011.906
MLA
Saigusa, S., Toiyama, Y., Tanaka, K., Yokoe, T., Okugawa, Y., Fujikawa, H., Matsusita, K., Kawamura, M., Inoue, Y., Miki, C., Kusunoki, M."Cancer-associated fibroblasts correlate with poor prognosis in rectal cancer after chemoradiotherapy". International Journal of Oncology 38.3 (2011): 655-663.
Chicago
Saigusa, S., Toiyama, Y., Tanaka, K., Yokoe, T., Okugawa, Y., Fujikawa, H., Matsusita, K., Kawamura, M., Inoue, Y., Miki, C., Kusunoki, M."Cancer-associated fibroblasts correlate with poor prognosis in rectal cancer after chemoradiotherapy". International Journal of Oncology 38, no. 3 (2011): 655-663. http://dx.doi.org/10.3892/ijo.2011.906