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BackgroundPancreatic cancer is a life-threatening malignant disease with significant diversity among geographic regions and races leading to distinct carcinogenesis and prognosis. Previous studies mainly focused on Western patients, while the genomic landscape of Oriental patients, especially Chinese, remained less investigated.MethodsA total of 408 pancreatic cancer patients were enrolled. A panel containing 436 cancer-related genes was used to detect genetic alterations in tumor samples.ResultsWe profiled the genomic alteration landscape of pancreatic duct adenocarcinoma (PDAC), intraductal papillary mucinous neoplasm (IPMN), periampullary carcinoma (PVC), and solid-pseudopapillary tumor (SPT). Comparison with a public database revealed specific gene mutations in Oriental PDAC patients including higher mutation rates of DNA damage repair-related genes. Analysis of mutational signatures showed potential heterogenous carcinogenic factors caused by diabetes mellitus. KRAS mutation, especially KRAS G12D mutation, was associated with poor survival, while patients not harboring the 17 significant copy number variations (CNVs) had a better prognosis. We further identified multiple correlations between clinicopathologic variables and genetic mutations, as well as CNVs. Finally, by network-based stratification, three classes of PDAC patients were robustly clustered. Among these, class 1 (characterized by the Fanconi anemia pathway) achieved the best outcome, while class 2 (involved in the platinum drug resistance pathway) suffered from the worst prognosis.ConclusionsIn this study, we reported for the first time the genetic alteration landscape of Oriental PDAC patients identifying many Oriental-specific alterations. The relationship between genetic alterations and clinicopathological factors as well as prognosis demonstrated important genomic impact on tumor biology. This study will help to optimize clinical treatment of Oriental PDAC patients and improve their survival.
Intraductal papillary mucinous neoplasms (IPMNs) are a heterogeneous group of neoplasms and represent the most common identifiable precursor lesions of pancreatic cancer. Clinical decision-making of the risk for malignant disease, including high-grade dysplasia and invasive carcinoma, is challenging. Moreover, discordance on the indication for resection exists between the contemporary guidelines. Furthermore, most of the current nomogram models for predicting malignant disease depend on endoscopic ultrasonography to evaluate the precise size of mural nodules. Thus, this study aimed to propose a model to predict malignant disease using variables from a noninvasive examination. We evaluated patients who underwent resection of pathologically confirmed IPMNs between November 2010 and December 2018 and had preoperative clinical data available for review. Based on binary multivariable logistic regression analysis, we devised a nomogram model to predict malignant IPMNs. The area under the receiver operating characteristics curve (AUC) was used to evaluate the discrimination power of the model. Of the 333 patients who underwent resection of IPMNs, 198 (59.5%) had benign and 135 (40.5%) had malignant IPMNs. Multivariable logistic regression analysis showed that cyst size, cyst location, cyst wall enhancement, multicystic lesion, diameter of main pancreatic duct, neutrophil-to-lymphocyte ratio, serum carbohydrate antigen 19-9, and carcinoembryonic antigen were significantly associated with malignancy. The nomogram, constructed based on these variables, showed excellent discrimination power with an AUC of 0.859 (95% CI: 0.818–0.900, P < 0.001). In conclusion, we have developed a nomogram consisting of a combination of cross-sectional imaging features and blood markers, variables that can readily be obtained by noninvasive examinations during the surveillance period, which can distinguish benign from malignant IPMNs. Nevertheless, external validation is warranted.
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