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This study investigates survival of patients diagnosed with pancreatic neuroendocrine tumor with liver metastases based on local treatment on the primary tumor. Patients diagnosed with stage IV PNET between 2010 and 2014 were identified from the Surveillance Epidemiology and End Results database. Cancer-Specific Survival and Overall Survival were examined. A total of 191 patients with pancreatic neuroendocrine tumor with liver metastases were included in this analysis. There were 47 patients (24.6%) who received surgical resection and 144 (75.4%) who did not. Patients with N1 stage was more likely to be treated with surgical resection. The results showed that surgical resection of primary tumor was associated with Cancer-Specific Survival (p = 0.028) and Overall Survival (p = 0.025) benefit. Not receiving surgery, being unmarried and N1 stage are factors associated with poor survival. This study reveals that local treatment on the primary benefits both Cancer-Specific Survival and Overall Survival in PNET patients with LM. This may be suggestive for the management on this patient population.

Background. The incidence of nonfunctional pancreatic neuroendocrine neoplasms (NF-pNENs) has been increasing annually. This study is aimed at investigating the clinicopathological characteristics and high-risk factors of NF-pNENs and the influence of surgical treatment on the prognosis of NF-pNEN patients with liver metastases. Methods. pNEN patients in this study were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. This study analyzed patients diagnosed with NF-pNENs from 2000 to 2017 who met the inclusion criteria. A retrospective analysis of the clinicopathological characteristics of NF-pNEN patients was conducted. Kaplan-Meier method was used to calculate the survival time. A multivariate Cox regression model was used to analyze the survival outcomes and risk factors. Results. From 2000 to 2017, the SEER database registered 10576 patients with pNENs and 1774 patients with liver metastases. Cox analysis revealed that age, sex, primary site, grade, tumor stage, surgery, tumor size, and liver metastasis were risk factors of prognosis, with grade being the most influential index. Patients with NF-pNENs with liver metastasis and no metastasis had different primary site, grade, and tumor size. In general, a higher grade was associated with a larger tumor and a greater risk of liver metastasis. Meanwhile, patients with liver metastasis showed that those with tumors originated from the tail of the pancreas had better prognoses than those with tumors originated from other parts. Surgical treatment can improve the prognosis of patients with liver metastases, despite the tumor grade. Conclusions. The incidence of pNENs has been increasing annually, and the liver has been the most common site of metastasis. Liver metastasis in patients with NF-pNENs, related to tumor size and grade, affected their long-term survival. Surgery significantly improved the prognosis of patients with liver metastases secondary to NF-pNENs with different grades.

BackgroundTransmembrane (TMEM) protein genes are a class of proteins that spans membranes and function to many physiological processes. However, there is very little known about TMEM gene expression, especially in cancer tissue. Using single-cell and bulk RNA sequence may facilitate the understanding of this poorly characterized protein genes in PDAC.MethodsWe selected the TMEM family genes through the Human Protein Atlas and characterized their expression by single-cell and bulk transcriptomic datasets. Identification of the key TMEM genes was performed through three machine learning algorithms: LASSO, SVM-RFE and RF-SRC. Then, we established TMEM gene riskscore and estimate its implication in predicting survival and response to systematic therapy. Additionally, we explored the difference and impact of TMEM gene expression in PDAC through immunohistochemistry and cell line research.Results5 key TMEM genes (ANO1, TMEM59, TMEM204, TMEM205, TMEM92) were selected based on the single-cell analysis and machine learning survival outcomes. Patients stratified into the high and low-risk groups based on TMEM riskscore, were observed with distinct overall survival in internal and external datasets. Moreover, through bulk RNA-sequence and immunohistochemical staining we verified the protein expression of TMEM genes in PDAC and revealed TMEM92 as an essential regulator of pancreatic cancer cell proliferation, migration, and invasion.ConclusionOur study on TMEM gene expression and behavior in PDAC has revealed unique characteristics, offering potential for precise therapeutic approaches. Insights into molecular mechanisms expand understanding of PDAC complexity and TMEM gene roles. Such knowledge may inform targeted therapy development, benefiting patients.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Recent evidence has shown that circular RNAs (circRNAs) play important roles in tissue development, gene transcription, signal regulation and tumorigenesis. However, whether circRNAs are involved in HCC progression and encode functional proteins remains largely unknown. In the present study, we aimed to explore the function and molecular mechanism of circRNAs in HCC. First, many circRNAs were found to be differentially expressed in HCC samples and paired adjacent normal liver tissues. The validation of dysregulated circRNAs by qRT-PCR revealed that circEPS15 expression was downregulated in HCC tissues, and the survival curves showed that low circEPS15 levels were associated with poor overall survival in HCC patients. Then, the overexpression of circEPS15 suppressed tumor cell invasion and migration by inhibiting the TJP1/CDH2/VIM signaling pathway and retarded cell cycle progression, which was confirmed by the Transwell culture system, wound healing assays, flow cytometry and western blot assays. After that, the spanning junction open reading frame in circEPS15 driven by IRES was shown to encode a novel protein, which was verified by western blotting with full-length, mutated, and truncated sequences of circEPS15 with a FLAG tag. Moreover, ceRNA analysis and qRT-PCR results suggest a possible circRNA (circEPS15)-miRNA-mRNA network in HCC. Collectively, our study reveals that endogenous circEPS15 plays a novel role in repressing HCC through the ceRNA network and encodes a functional protein.