Prognostic relevance of UCH-L1 and α-internexin in pancreatic neuroendocrine tumors

Abstract

Prognostic biomarkers for the pancreatic neuroendocrine tumors are needed. Proteomic study on insulinoma has been rarely reported. We identified the differential expression of proteins between insulinoma and their paired tissues by proteomic analysis, and evaluated the prognostic significance of specific proteins in pancreatic neuroendocrine tumors including insulinoma. The differential expression of select proteins was validated in more than 300 tumors using immunohistochemical staining and western blot. Methylation of UCH-L1 promoter in tumors was examined by methylation specific PCR and validated by sequencing. The concurrent expression of UCH-L1 and α-internexin was correlated with the prognosis in 2 independent collectives of patients with tumors. Sixty-two and 219 proteins were significantly down-regulated and up-regulated in insulinomas, respectively. Demethylation of UCH-L1 promoter was associated with UCH-L1 expression in tumors (p = 0.002). The concurrent expression of UCH-L1 and α-internexin in pancreatic neuroendocrine tumors was significantly associated with better overall survival and disease-free survival in the combination of both cohorts (log rank p = 3.90 × 10−4 and p = 3.75 × 10−5, respectively) and in each of cohorts. The prognostic value of both proteins was also validated in patients with stage II and III tumors (p = 0.017 and p = 0.006, respectively). The proteins UCH-L1 and α-internexin could be independent prognostic biomarkers of pancreatic neuroendocrine tumors.

A novel liver metastasis-correlated protein of pancreatic neuroendocrine neoplasm (PanNEN) discovered by proteomic analysis

“…However, only two studies on the proteomics of PanNEN have been reported. One was a proteomic analysis between insulinoma with and without lymph node metastases [ 15 ], and the other one between the tumor tissue of insulinoma and normal tissue [ 16 ]. There has been no study of proteomic analysis comparing the primary tumor of PanNEN with liver metastasis.…”

Candidate Genes Identified by Constructing a Weighted Gene Co-Expression Network and Key Prognostic Factors of Pancreatic Adenocarcinoma

“…It may control pathologic T by means of promoting the differentiation and maturation of PAAD cells. INA encoded internexin neuronal intermediate lament protein alpha, loss of the expression of alpha-internexin was closely related to aggressiveness of tumors and patient's adverse prognosis (Wang et al, 2018), and alpha-internexin could be independent prognostic biomarker of pancreatic neuroendocrine tumors (Song et al, 2017). The expression of module genes could signi cantly inhibit the increase of tumor volume and the expansion of involvement range of adjacent tissues, providing new target sites for future neoadjuvant chemotherapy.…”

Analysis of methylation‐driven genes for predicting the prognosis of patients with head and neck squamous cell carcinoma

“…These markers may serve as potential biomarkers or drug targets for early diagnosis and prognostic assessment. Alpha‐internexin ( INA ) has often been reported to be a prognostic marker of neuroendocrine neoplasms . In addition, INA plays an important role in the occurrence and development of brain tumors .…”