Identification and initial validation of neuroendocrine differentiation as a novel prognostic factor in stage II colorectal cancer patients.

ABSTRACT

Neuroendocrine differentiation is often found in colorectal cancer but its impact on prognosis remains controversial. This study explored the association between neuroendocrine differentiation and prognosis in stage II/III colorectal cancer patients. METHODS: Between 2012 and 2018, a total of 3,441 stage II/III colorectal cancer patients were included for analysis. To verify neuroendocrine differentiation, immunohistochemistry was performed to explore the expression of chromogranin A and synaptophysin in colorectal cancer. In addition, the difference in overall survival between groups was analyzed. A Kaplan-Meier analysis was used to determine the clinicopathological characteristics significantly correlated with survival, and a Cox proportional hazards analysis was used to identify factors independently affecting overall survival prognosis. Furthermore, the findings were validated by the Gene Expression Omnibus database. RESULTS: Among the 3441 stage II/III colorectal cancer patients, in comparison to patients with neuroendocrine differentiation (+), patients with neuroendocrine differentiation (+) had a poorer prognosis (P = 0.001). Furthermore, multivariate survival analysis of stage II cases revealed that tumor differentiation (P = 0.018), nerve invasion (P < 0.001) and neuroendocrine differentiation (+) (P = 0.002) were independent prognostic factors. Moreover, the prognosis of patients with neuroendocrine differentiation (+) was similar to that of patients with high-risk factors in stage II cases (P = 0.639). High chromogranin A expression was correlated with poor prognosis in stage II colorectal cancer patients in the Gene Expression Omnibus database (P < 0.001). CONCLUSION: The prognosis of colorectal cancer with neuroendocrine differentiation (+) was poor, especially in stage II colorectal cancer patients. neuroendocrine differentiation might be another high-risk factor for the prognosis of stage II colorectal cancer patients.