Relationship between autophagy and perineural invasion, clinicopathological features, and prognosis in pancreatic cancer

Abstract

Aim: To investigate the relationship between autophagy and perineural invasion (PNI), clinical features, and prognosis in patients with pancreatic cancer.

Methods: Clinical and pathological data were retrospectively collected from 109 patients with pancreatic ductal adenocarcinoma who underwent radical resection at the First Affiliated Hospital of Zhengzhou University from January 2011 to August 2016. Expression levels of the autophagy-related protein microtubule-associated protein 1A/1B-light chain 3 (LC3) and PNI marker ubiquitin carboxy-terminal hydrolase (UCH) in pancreatic cancer tissues were detected by immunohistochemistry. The correlations among LC3 expression, PNI, and clinical pathological features in pancreatic cancer were analyzed. The patients were followed for further survival analysis.

Results: In 109 cases of pancreatic cancer, 68.8% (75/109) had evidence of PNI and 61.5% (67/109) had high LC3 expression. PNI was associated with lymph node metastasis, pancreatitis, and CA19-9 levels (P < 0.05). LC3 expression was related to lymph node metastasis (P < 0.05) and was positively correlated with neural invasion (P < 0.05, r = 0.227). Multivariate logistic regression analysis indicated that LC3 expression, lymph node metastasis, pancreatitis, and CA19-9 level were factors that influenced neural invasion, whereas only neural invasion itself was an independent factor for high LC3 expression. Univariate analysis showed that LC3 expression, neural invasion, and CA19-9 level were related to the overall survival of pancreatic cancer patients (P < 0.05). Multivariate COX regression analysis indicated that PNI and LC3 expression were independent risk factors for poor prognosis in pancreatic cancer (P < 0.05).

Conclusion: PNI in patients with pancreatic cancer is positively related to autophagy. Neural invasion and LC3 expression are independent risk factors for pancreatic cancer with a poor prognosis.

Keywords: Autophagy; Clinical pathological features; Pancreatic cancer; Perineural invasion; Prognosis.

Figure 1

Representative immunohistochemical results of microtubule-associated protein 1A/1B-light chain 3 and perineural invasion. A: Negative expression of LC3 in normal paraneoplastic pancreatic tissue (× 200); B: Negative expression of LC3 in pancreatic cancer tissue (× 200); C: Weakly positive expression of LC3 in pancreatic cancer tissue (× 200); D: Moderately positive expression of LC3 in pancreatic cancer tissue (× 200); E: Strongly positive expression of LC3 in pancreatic cancer tissue (× 200); F and G: Perineural invasion in pancreatic cancer tissues (× 400, arrow represents cancer cells infiltrating into nerve tissue); H: Pancreatic cancer cells with high LC3 expression enclosing and invading into nerve tissue (× 200, arrow represents cancer cells infiltrating into nerve tissue); I: Pancreatic cancer cells with high LC3 expression enclosing and invading into nerve tissue (× 400, arrow represents cancer cells infiltrating into nerve tissue). LC3: Microtubule-associated protein 1A/1B-light chain 3.

Figure 2

Kaplan-Meier estimates of overall survival in patients who underwent radical surgery. A: The overall survival rate of the LC3 low-expression group was better than that of the high-expression group (P < 0.05); B: The overall survival rate of the patients without nerve invasion group was better than that of those with nerve infiltration (P < 0.05).