Neuroendocrine differentiation (NED) may serve as a prognostic factor in colorectal cancer; however, the prognostic relevance of NED remains controversial. The aim of the present study was to determine whether NED influenced the survival of patients in colorectal cancer while exploring its potential interactions with other clinicopathological features.
Patients with primary stage I to IV colorectal adenocarcinoma ranging between 2010 and 2015 were identified using the Surveillance, Epidemiology, and End Results database. The Kaplan-Meier technique, Cox proportional hazards model, propensity score matching, and stratification analyses were employed in this study.
A total of 94,291 patients (including 101 patients with NED and 94,190 patients without NED) were included. In the univariable analyses, NED was found to be correlated with a significantly poorer overall survival (hazard ratio (HR) of death = 3.09, 95% CI 2.42-3.95, P < 0.001) and cancer-specific survival (HR of death = 3.77, 95% CI 2.94-4.83, P < 0.001). Moreover, NED remained independently correlated with overall survival (HR of death = 1.84, 95% CI 1.34-2.51, P < 0.001) and cancer-specific survival (HR of death = 2.01, 95% CI 1.45-2.79, P < 0.001) after adjusting in multivariable and propensity score analyses. Furthermore, further stratification analyses indicated that the influence of NED on survival was not affected by tumor location, differentiation, T stage, and distant metastasis status; however, it was found to be associated with lymph node metastasis.
NED is associated with poor survival outcomes among colorectal cancer patients, especially in those with positive lymph nodes.

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