Résumé
P4HA2, one of the important genes encoding the α subunit of collagen prolyl 4-hydroxylase (C-P4H) , is overexpressed in a variety of tumors and promotes tumor progression, and its high expression correlates with the poor prognosis of patients. In different tumors, P4HA2 can promote the proliferation, migration and invasion of tumor cells, increase the proportion of cancer stem cell population, and promote tumor cells to escape from immune system. An in-depth understanding of the role of P4HA2 in tumor progression may provide new ideas and insights for targeting P4HA2 to prevent or reverse tumor progression.
Résumé
Objective: To determine whether microtubule-associated protein 2 (MAP2) and microtubule-associated protein 1B (MAP1B) could be prognostic biomarkers for patients with pancreatic neuroendocrine tumors (PNETs). Methods:With immunohisto-chemical staining, the expressions of MAP2 and MAP1B were examined in 193 and 120 primary tumors and peritumoral tissues, re-spectively. Then, the relationship between the expression of each protein and clinicopathological characteristics, including prognosis was analyzed. Results:MAP2 and MAP1B were expressed in 88 of 193 (45.6%) and 77 of 120 (64.2%) tumors, respectively. The expres-sion of MAP2 was significantly associated with the favorable overall survival of patients with PNETs (P=0.012). Moreover, MAP2 expres-sion was associated with the improved overall survival in a subset of patients with stageⅡand stageⅢtumors (P=0.017). The MAP1B expression did not correlate with other clinicopathological features and prognosis. Conclusion:MAP2 could be a novel, independent prognostcbiomarker for PNETs.
Résumé
Gastrointestinal neuroendocrine tumors are a group of highly heterogeneous tumors. Their incidences have increased in the Western countries as well as in Asia for years. In recent years, predominant progression has been made in the basic and translational studies on gastrointestinal neuroendocrine tumors. Gastric neuroendocrine neoplasmas are classified as four types: type I( occurs on the basis of autoimmune atrophic gastritis, type II( clinically manifests as multiple endocrine tumor type I( and Zollinger-Ellison syndrome, type III( is sporadic neuroendocrine neoplasmas, and type IIII( is neuroendocrine carcinoma. According to the location of primary tumor, intestinal neuroendocrine neoplasmas are classified as small intestine neuroendocrine neoplasmas and colorectal neuroendocrine neoplasmas. The latest finding shows that familial type I( gastric neuroendocrine neoplasmas exists homozygous missense mutation (c.2107C>T) of ATP4A gene. A number of researches focus on small intestine neuroendocrine neoplasmas recently. The chromosome instability, whole genome low methylation and abnormal expression of microRNA can be found in small intestine neuroendocrine neoplasmas. Part of them presents heterozygous mutations and loss of heterozygosity of CDKN1B gene. A recent study showed the heterozygous mutations of IPMK gene (c.990-993del) in familial small intestinal neuroendocrine neoplasmas. PROX1 and Annexin A1 may be involved in the malignant progression of rectal neuroendocrine neoplasmas via the Wnt pathway. The molecular mechanism of gastrointestinal neuroendocrine carcinoma is significantly different from gastrointestinal neuroendocrine tumors. The expression of mTOR, thymidylate synthase and PD-L1 protein, and gene mutation of BRAF V600E and KRAS have been exclusively found in gastrointestinal neuroendocrine carcinoma. The expression of thymidylate synthase, p27, p16, Gα15, PROX1 and Annexin A1 in gastrointestinal neuroendocrine neoplasmas is associated with the prognosis of these patients. Neurokinin A is a specific peripheral blood tumor biomarker for the prognosis and response to the treatment of patients with small intestinal neuroendocrine neoplasmas. INSL5 can be used as a unique biomarker for rectal neuroendocrine neoplasmas.