Clinical pathological characteristics and expression of 328 proteins and their impact on survival in over 20,000 cases of esophageal squamous cell carcinoma and colorectal adenocarcinoma

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Esophageal squamous carcinoma and colorectal adenocarcinoma are both the most common digestive tract tumors in China, and they share certain similarities in genetic susceptibility, major risk factors and molecular mechanisms. However, comparative studies on these two tumors with large sample sizes are still lacking. This study was conducted to analyze the differences between the two tumors in clinicopathological features and tumor-associated protein expression, their impact on survival, and to provide a basis for the identification of molecular markers of early detection and targeted therapy. In this study, 26 tumor-associated proteins were selected from 20,097 patients with esophageal squamous carcinoma and colorectal adenocarcinoma. The χ2 test was applied to compare the differences between the two tumors in terms of clinicopathological features and protein expression. The Kaplan-Meier survival analysis and Cox regression analysis were used to compare the relationship between the clinicopathological features and protein expression and the survival of patients. Significant differences were found between patients with esophageal squamous carcinoma and those with colorectal adenocarcinoma in gender, age, degree of differentiation, margins, TNM stage, vascular embolism, neurological invasion and family history. In addition, age, lymph node metastasis, TNM stage and degree of differentiation had similar effects on the prognosis of patients with both tumors, and gender had opposite effects on the prognosis of patients with both tumors. Of the 26 tumor-associated proteins examined in 100 and more cases, 19 proteins were differentially expressed in the two tumors. Further Kaplan-Meier survival analysis of these 26 proteins showed that in esophageal squamous carcinoma, CK (P=0.005) and EGFR (P=0.002) and Syn (P=0.002)-positive patients had a poorer prognosis than negative patients, and CK8/18 (P=0.039) and Her-2 (P=0.002) positive patients had a better prognosis than negative patients. In colorectal cancer, Syn (P=0.002) and CK7 (P<0.001) positive patients had poorer prognosis than negative patients, and VEGF positive patients had better prognosis than VEGF negative patients (P=0.003).We further applied multivariate Cox regression analysis to evaluate the effect of survival-related proteins on the prognosis of patients with esophageal squamous carcinoma or colorectal adenocarcinoma, and found that Syn positivity (HR=3.860, 95%CI (1.377‒11.144), P=0.013) was an independent risk factor for the prognosis of patients with esophageal squamous carcinoma; in colorectal adenocarcinoma, CK7 positivity (HR=2.446, 95%CI (1.427‒4.193), P=0.001) and Syn positivity (HR=3.492, 95%CI (1.377‒8.854), P=0.008) were independent risk factors for the prognosis of colorectal adenocarcinoma patients, and VEGF positivity (HR=0.007, 95%CI (0.001‒0.337), P=0.013) was an independent protective factor for the prognosis of colorectal adenocarcinoma patients. Syn protein was found to be an independent prognostic factor in both tumors. These important findings provide an important reference for the clinical personalized diagnosis and treatment of the two types of tumors, as well as objective evidence of the intrinsic connection of the two types of tumors, which deepens our understanding of the intrinsic connection between the two types of tumors.

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