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Expression of cocaine- and amphetamine-regulated transcript is associated with worse survival in small bowel
Kalle Landerholm1, Liliya Shcherbina, Sture E Falkmer
1Department of Surgery, Ryhov Hospital, Jönköping, Sweden. kalle.landerholm@lj.se
Purpose:
Cocaine- and amphetamine-regulated transcript (CART) peptide exerts several regulatory functions acting both as neurotransmitter and hormone. We recently showed that CART is expressed in various neuroendocrine tumors, including small bowel carcinoids. The main objective of the present study was to examine whether CART expression is associated with survival in patients with small bowel carcinoid. Secondary aims were to assess whether CART expression is associated with other tumor characteristics or clinical symptoms.
Experimental Design:
Specimens from 97 patients with small bowel carcinoids were examined for CART expression using immunohistochemistry. A CART score was introduced on the basis of the proportion of CART immunoreactive cells. On inclusion, specimens were examined by routine histopathologic methods and detailed clinical patient data were retrieved. The effect of CART on cell viability was assessed in vitro using two intestinal tumor cell lines.
Results:
Expression of CART (P = 0.011) and increasing CART score (P = 0.033) were associated with worse disease-specific survival. Adjusting for age, disease stage, and tumor grade in multivariable analysis, CART expression was still associated with worse survival [Low CART HR, 5.47; 95% confidence interval (CI), 0.71-42.46; and High CART HR, 9.44; 95% CI, 1.14-78.14]. CART expression was not associated with patient age, disease stage, tumor grade, or any presenting symptom. Supporting our clinical data, we found that CART promoted tumor cell viability in vitro in two different tumor cell lines.
Conclusion:
Expression of CART in small bowel carcinoid tumors is associated with worse survival.
Insights
Cocaine- and amphetamine-regulated transcript (CART) peptide expression in small bowel carcinoid tumors is linked to poorer patient survival. Higher CART expression correlates with worse disease-specific survival outcomes in these neuroendocrine tumors.
Area of Science:
- Neuroendocrinology
- Oncology
- Molecular Biology
Background:
- Cocaine- and amphetamine-regulated transcript (CART) peptide functions as a neurotransmitter and hormone.
- CART is expressed in various neuroendocrine tumors, including small bowel carcinoids.
- Previous research indicated CART expression in small bowel carcinoid tumors.
Purpose of the Study:
- To investigate the association between CART expression and survival in patients with small bowel carcinoid.
- To determine if CART expression correlates with tumor characteristics.
- To assess the relationship between CART expression and clinical symptoms.
Main Methods:
- Immunohistochemistry was used to examine CART expression in 97 small bowel carcinoid specimens.
- A CART score was developed based on the proportion of CART-immunoreactive cells.
- In vitro studies assessed CART's effect on intestinal tumor cell viability.
Main Results:
- CART expression and increasing CART score were significantly associated with worse disease-specific survival (P = 0.011 and P = 0.033, respectively).
- Multivariable analysis confirmed CART expression as an independent predictor of worse survival.
- CART expression did not correlate with patient age, disease stage, tumor grade, or presenting symptoms.
- In vitro, CART promoted tumor cell viability in two intestinal tumor cell lines.
Conclusions:
- CART expression in small bowel carcinoid tumors is a significant indicator of poorer patient survival.
- CART peptide may play a role in promoting tumor cell viability in small bowel carcinoids.
