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Prediagnosis Use of Statins Associates With Increased Survival Times of Patients With Pancreatic Cancer.

ABSTRACT: BACKGROUND & AIMS:Statin medications, most commonly prescribed to reduce lipid levels and prevent cardiovascular disease, may be associated with longer survival times of patients with cancer. However, the association of statins with outcomes of patients with pancreatic adenocarcinoma is not clear. METHODS:We analyzed the association of statin use before a diagnosis of pancreatic cancer with survival times of 648 participants in the Nurses' Health Study and Health Professionals Follow-up Study who were diagnosed with pancreatic adenocarcinoma from 2000 through 2013. We estimated hazard ratios (HRs) for overall mortality using Cox proportional hazards models with adjustment for potential confounders. We assessed the temporal association between prediagnosis statin use and cancer survival by 2-year lag periods to account for a possible latency period between statin use and cancer survival. RESULTS:Regular statin use before diagnosis of pancreatic cancer was associated with modestly prolonged survival compared with nonregular use (adjusted HR, 0.82; 95% CI, 0.69-0.97; P = .02). A 1-month longer median survival was observed in regular statin users compared with nonregular users. Regular statin use within the 2 years prior to cancer diagnosis was most strongly associated with longer survival. We observed no statistically significant effect modification by smoking status, body mass index, diabetes, or cancer stage (all Pinteraction > .53). Regular statin use before diagnosis was similarly associated with survival in the Nurses' Health Study (HR, 0.79; 95% CI, 0.64-0.97) and Health Professionals Follow-up Study (HR, 0.86; 95% CI, 0.63-1.15). CONCLUSIONS:Regular statin use before diagnosis of pancreatic cancer was associated with modest increases in survival times in 2 large prospective cohort studies.

SUBMITTER: Hamada T

PROVIDER: S-EPMC6056316 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Prediagnosis Use of Statins Associates With Increased Survival Times of Patients With Pancreatic Cancer.

Hamada Tsuyoshi T Khalaf Natalia N Yuan Chen C Morales-Oyarvide Vicente V Babic Ana A Nowak Jonathan A JA Qian Zhi Rong ZR Ng Kimmie K Rubinson Douglas A DA Kraft Peter P Giovannucci Edward L EL Stampfer Meir J MJ Fuchs Charles S CS Ogino Shuji S Wolpin Brian M BM

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 20180221 8

<h4>Background & aims</h4>Statin medications, most commonly prescribed to reduce lipid levels and prevent cardiovascular disease, may be associated with longer survival times of patients with cancer. However, the association of statins with outcomes of patients with pancreatic adenocarcinoma is not clear.<h4>Methods</h4>We analyzed the association of statin use before a diagnosis of pancreatic cancer with survival times of 648 participants in the Nurses' Health Study and Health Professionals Fol ...[more]

PMID: 29474971

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Project description:BackgroundMethyltransferase-like 3 (METTL3) expression could be found in various normal and cancerous tissues. As of now, the clinical significance of METTL3 expression in human pancreatic cancer (PC) tissues still remains to be understood. Our present study aims to investigate the prognostic value and clinical implications of METTL3 expression in PC tissues.MethodsThe TCGA, GTEx, and GEO public databases were used to study the mRNA expression level of the m6A family members and its relationship among PC tissues and normal pancreatic tissue. The immunohistochemistry was used to analyze the difference of METTL3 expression between cancer tissues and adjacent normal tissues. The prognostic value was evaluated by using the Log-rank survival analysis and Cox model analysis. PAAD samples from TCGA and GEO databases were used to perform the immune infiltration analysis and gene set enrichment analysis based on the genes that were highly correlated with METTL3.ResultsBased on the analysis of TCGA, GTEx, and GEO public database, we found that the m6A family members showed a higher correlation in PC tissues compared to normal pancreatic tissues, and the mRNA expression level of the m6A family members showed a significant difference between PC tissues and adjacent normal tissues. Moreover, scRNA-seq data indicated that METTL3 showed a higher expression level in malignant epithelial cells. Our immunohistochemistry results also confirmed that the intensity of METTL3 immunostaining in PC tissues was significantly higher than that in adjacent normal tissues (P = 0.015). The overall survival (OS) of PC patients with high expression of METTL3 protein were significantly poorer than those with low expression of METTL3 protein (HR = 1.788, 95% CI 1.071-2.984, P = 0.026). Further analysis of PC data from the database showed that METTL3 expression was associated with a variety of tumor-infiltrating immune cells and was involved in m6A modification and metabolism in PC tissues.ConclusionIncreased METTL3 expression at the protein level could be found in PC tissues, suggesting that the METTL3 expression was involved in the progression of PC and could serve as an important marker for prognostic prediction of this malignancy.

Project description:Despite prognostic grading and staging systems, it is a challenge to predict outcomes for patients with pancreatic neuroendocrine tumors (PanNETs). Sequencing studies of PanNETs have identified alterations in death domain-associated protein (DAXX) and alpha-thalassemia/mental retardation X-linked chromatin remodeler (ATRX). In tumors, mutations in DAXX or ATRX and corresponding loss of protein expression correlate with shorter times of disease-free survival and disease-specific survival of patients. However, DAXX or ATRX proteins were lost in only 50% of distant metastases analyzed. We performed whole-exome sequencing analyses of 20 distant metastases from 20 patients with a single nonsyndrome, nonfunctional PanNET. We found distant metastases contained alterations in multiple endocrine neoplasia type 1 (MEN1) (n = 8), ATRX (n = 5), DAXX (n = 5), TSC2 (n = 3), and DEP domain containing 5 (DEPDC5) (n = 3). We found copy number loss of cyclin dependent kinase inhibitor 2A (CDKN2A) in 15 metastases (75%) and alterations in genes that regulate chromatin remodeling, including set domain containing 2 (SETD2) (n = 4), AT-rich interaction domain 1A (ARID1A) (n = 2), chromodomain helicase DNA binding protein 8 (CHD8) (n = 2), and DNA methyl transferase 1 (DNMT1) (n = 2). In a separate analysis of 347 primary PanNETs, we found loss or deletion of DAXX and ATRX, disruption of SETD2 function (based on loss of H3 lysine 36 trimethylation), loss of ARID1A expression or deletions in CDKN2A in 81% of primary PanNETs with distant metastases. Among patients with loss or deletion of at least 1 of these proteins or genes, 39% survived disease-free for 5 years and 44% had disease-specific survival times of 10 years. Among patients without any of these alterations, 98% survived disease-free for 5 years and 95% had disease-specific survival times of 10 years. Therefore, primary PanNETs with loss of DAXX, ATRX, H3 lysine 36 trimethylation, ARID1A, and/or CDKN2A associate with shorter survival times of patients. Our findings indicate that alterations in chromatin-remodeling genes and CDKN2A contribute to metastasis of PanNETs.

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Prediagnosis Use of Statins Associates With Increased Survival Times of Patients With Pancreatic Cancer.

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Prediagnosis Use of Statins Associates With Increased Survival Times of Patients With Pancreatic Cancer.

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