Background
Although a substantial increase in the survival of patients with other cancers has been observed in recent decades, pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest diseases. No effective screening approach exists.
Methods
Differential exosomal long noncoding RNAs (lncRNAs) isolated from the serum of patients with PDAC and healthy individuals were profiled to screen for potential markers in liquid biopsies. The functions of LINC00623 in PDAC cell proliferation, migration and invasion were confirmed through in vivo and in vitro assays. RNA pulldown, RNA immunoprecipitation (RIP) and coimmunoprecipitation (Co-IP) assays and rescue experiments were performed to explore the molecular mechanisms of the LINC00623/NAT10 signaling axis in PDAC progression.
Results
A novel lncRNA, LINC00623, was identified, and its diagnostic value was confirmed, as it could discriminate patients with PDAC from patients with benign pancreatic neoplasms and healthy individuals. Moreover, LINC00623 was shown to promote the tumorigenicity and migratory capacity of PDAC cells in vitro and in vivo. Mechanistically, LINC00623 bound to N-acetyltransferase 10 (NAT10) and blocked its ubiquitination-dependent degradation by recruiting the deubiquitinase USP39. As a key regulator of N4-acetylcytidine (ac4C) modification of mRNA, NAT10 was demonstrated to maintain the stability of oncogenic mRNAs and promote their translation efficiency through ac4C modification.
Conclusions
Our data revealed the role of LINC00623/NAT10 signaling axis in PDAC progression, showing that it is a potential biomarker and therapeutic target for PDAC.
Carcinoma arising from a mucinous cystic neoplasm (MCN) of the pancreas is termed MCN with associated invasive carcinoma (MCN‐AIC) in the fifth WHO classification of digestive tumors (2019). The prognosis of this malignancy varies depending on the relationship of the invasive carcinoma to the cyst capsule, but limited data are available. This study identified 165 surgically resected MCNs including 15 MCN‐AICs from a single center between 2008 and 2018 and analyzed their clinicopathologic features. The results confirmed that non‐invasive MCNs were completely cured by surgery. All MCN‐AICs showing an encapsulated invasion pattern (defined as invasive carcinoma limited to the ovarian‐type stroma, cystic septa, and capsule) had an excellent prognosis with a 5‐year survival rate of 100%, even when the size of the invasive component was up to stage T2. By contrast, MCN‐AICs with extracapsular involvement had unfavorable clinical outcomes. Our study demonstrates that the pattern of invasion of MCN‐AIC can predict patient prognosis. Pathologic stage T1 and T2 encapsulated MCN‐AICs may be completely cured with surgical resection alone or when combined with postoperative chemotherapy.
Mucinous cystic neoplasm (MCN) of the pancreas is an exocrine cystic tumor with a potential of harboring malignancy. The latest World Health Organization classification of tumors of digestive system designates malignant MCN as MCN with associated invasive carcinoma (MCN-AIC). Since its separation from other pancreatic cystic tumors in 1978, much progress has been made in our understanding of MCN in epidemiology, clinical and pathological features, biological behavior, as well as prognostic characteristics. This review aims to summarize the current knowledge of MCN and MCN-AIC.
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