Neurogenesis in colorectal cancer is a marker of aggressive tumor behavior and poor outcomes

Daniel Albo, Catherine L. Akay, Christy L. Marshall, Jonathan A. Wilks, Gordana Verstovsek, Hao Liu, Neeti Agarwal, David H. Berger, Gustavo E. Ayala

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

BACKGROUND: Colorectal cancer staging criteria do not rely on examination of neuronal tissue. The authors previously demonstrated that perineural invasion is an independent prognostic factor of outcomes in colorectal cancer. For the current study, they hypothesized that neurogenesis occurs in colorectal cancer and portends an aggressive tumor phenotype. METHODS: In total, samples from 236 patients with colorectal cancer were used to create a tissue array and database. Tissue array slides were immunostained for protein gene product 9.5 (PGP9.5) to identify nerve tissue. The correlation between markers of neurogenesis and oncologic outcomes was determined. The effect of colorectal cancer cells on stimulating neurogenesis in vitro was evaluated using a dorsal root ganglia coculture model. RESULTS: Patients whose tumors exhibited high degrees of neurogenesis had 50% reductions in 5-year overall survival and disease-free survival compared with patients whose tumors contained no detectable neurogenesis (P =.002 and P =.006, respectively). Patients with stage II disease and high degrees of neurogenesis had greater reductions in 5-year overall survival and disease-free survival compared with lymph node-negative patients with no neurogenesis (P =.002 and P =.008, respectively). Patients with stage II disease and high degrees of neurogenesis had lower 5-year overall survival and disease-free survival compared with patients who had stage III disease with no neurogenesis (P =.01 and P =.008, respectively). Colorectal cancer cells stimulated neurogenesis and exhibited evidence of neuroepithelial interactions between nerves and tumor cells in vitro. CONCLUSIONS: Neurogenesis in colorectal cancer appeared to play a critical role in colorectal cancer progression. Furthermore, the current results indicated that neurogenesis functions as an independent predictor of outcomes and may play a role in therapy stratification for patients with lymph node-negative disease.

Original languageEnglish (US)
Pages (from-to)4834-4845
Number of pages12
JournalCancer
Volume117
Issue number21
DOIs
StatePublished - Nov 1 2011
Externally publishedYes

Fingerprint

Neurogenesis
Tumor Biomarkers
Colorectal Neoplasms
Disease-Free Survival
Survival
Neoplasms
Lymph Nodes
Nerve Tissue
Neoplasm Staging
Spinal Ganglia
Coculture Techniques
Databases

Keywords

  • colorectal cancer
  • nerve density
  • neuroepithelial interaction in tumor stroma
  • neurogenesis
  • outcomes
  • therapy stratification

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Albo, D., Akay, C. L., Marshall, C. L., Wilks, J. A., Verstovsek, G., Liu, H., ... Ayala, G. E. (2011). Neurogenesis in colorectal cancer is a marker of aggressive tumor behavior and poor outcomes. Cancer, 117(21), 4834-4845. https://doi.org/10.1002/cncr.26117

Neurogenesis in colorectal cancer is a marker of aggressive tumor behavior and poor outcomes. / Albo, Daniel; Akay, Catherine L.; Marshall, Christy L.; Wilks, Jonathan A.; Verstovsek, Gordana; Liu, Hao; Agarwal, Neeti; Berger, David H.; Ayala, Gustavo E.

In: Cancer, Vol. 117, No. 21, 01.11.2011, p. 4834-4845.

Research output: Contribution to journalArticle

Albo, D, Akay, CL, Marshall, CL, Wilks, JA, Verstovsek, G, Liu, H, Agarwal, N, Berger, DH & Ayala, GE 2011, 'Neurogenesis in colorectal cancer is a marker of aggressive tumor behavior and poor outcomes', Cancer, vol. 117, no. 21, pp. 4834-4845. https://doi.org/10.1002/cncr.26117
Albo D, Akay CL, Marshall CL, Wilks JA, Verstovsek G, Liu H et al. Neurogenesis in colorectal cancer is a marker of aggressive tumor behavior and poor outcomes. Cancer. 2011 Nov 1;117(21):4834-4845. https://doi.org/10.1002/cncr.26117
Albo, Daniel ; Akay, Catherine L. ; Marshall, Christy L. ; Wilks, Jonathan A. ; Verstovsek, Gordana ; Liu, Hao ; Agarwal, Neeti ; Berger, David H. ; Ayala, Gustavo E. / Neurogenesis in colorectal cancer is a marker of aggressive tumor behavior and poor outcomes. In: Cancer. 2011 ; Vol. 117, No. 21. pp. 4834-4845.
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abstract = "BACKGROUND: Colorectal cancer staging criteria do not rely on examination of neuronal tissue. The authors previously demonstrated that perineural invasion is an independent prognostic factor of outcomes in colorectal cancer. For the current study, they hypothesized that neurogenesis occurs in colorectal cancer and portends an aggressive tumor phenotype. METHODS: In total, samples from 236 patients with colorectal cancer were used to create a tissue array and database. Tissue array slides were immunostained for protein gene product 9.5 (PGP9.5) to identify nerve tissue. The correlation between markers of neurogenesis and oncologic outcomes was determined. The effect of colorectal cancer cells on stimulating neurogenesis in vitro was evaluated using a dorsal root ganglia coculture model. RESULTS: Patients whose tumors exhibited high degrees of neurogenesis had 50{\%} reductions in 5-year overall survival and disease-free survival compared with patients whose tumors contained no detectable neurogenesis (P =.002 and P =.006, respectively). Patients with stage II disease and high degrees of neurogenesis had greater reductions in 5-year overall survival and disease-free survival compared with lymph node-negative patients with no neurogenesis (P =.002 and P =.008, respectively). Patients with stage II disease and high degrees of neurogenesis had lower 5-year overall survival and disease-free survival compared with patients who had stage III disease with no neurogenesis (P =.01 and P =.008, respectively). Colorectal cancer cells stimulated neurogenesis and exhibited evidence of neuroepithelial interactions between nerves and tumor cells in vitro. CONCLUSIONS: Neurogenesis in colorectal cancer appeared to play a critical role in colorectal cancer progression. Furthermore, the current results indicated that neurogenesis functions as an independent predictor of outcomes and may play a role in therapy stratification for patients with lymph node-negative disease.",
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AB - BACKGROUND: Colorectal cancer staging criteria do not rely on examination of neuronal tissue. The authors previously demonstrated that perineural invasion is an independent prognostic factor of outcomes in colorectal cancer. For the current study, they hypothesized that neurogenesis occurs in colorectal cancer and portends an aggressive tumor phenotype. METHODS: In total, samples from 236 patients with colorectal cancer were used to create a tissue array and database. Tissue array slides were immunostained for protein gene product 9.5 (PGP9.5) to identify nerve tissue. The correlation between markers of neurogenesis and oncologic outcomes was determined. The effect of colorectal cancer cells on stimulating neurogenesis in vitro was evaluated using a dorsal root ganglia coculture model. RESULTS: Patients whose tumors exhibited high degrees of neurogenesis had 50% reductions in 5-year overall survival and disease-free survival compared with patients whose tumors contained no detectable neurogenesis (P =.002 and P =.006, respectively). Patients with stage II disease and high degrees of neurogenesis had greater reductions in 5-year overall survival and disease-free survival compared with lymph node-negative patients with no neurogenesis (P =.002 and P =.008, respectively). Patients with stage II disease and high degrees of neurogenesis had lower 5-year overall survival and disease-free survival compared with patients who had stage III disease with no neurogenesis (P =.01 and P =.008, respectively). Colorectal cancer cells stimulated neurogenesis and exhibited evidence of neuroepithelial interactions between nerves and tumor cells in vitro. CONCLUSIONS: Neurogenesis in colorectal cancer appeared to play a critical role in colorectal cancer progression. Furthermore, the current results indicated that neurogenesis functions as an independent predictor of outcomes and may play a role in therapy stratification for patients with lymph node-negative disease.

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