Seromic Mucin Signature for the Early Diagnosis of Pancreatic Cancer

ABSTRACT Pancreatic cancerPCis an extremely aggressive malignancy with one of the worst prognoses of all cancersWith marked resistance to chemoand radiotherapiessurgery is the only curative optionIn patients with localized diseasecomplete surgical resection provides five year survival rate ofHoweverandgtof patients are diagnosed with unresectable primary tumors and or distant metastasisThe major cause for late clinical presentationand the resulting high mortalityis the lack of a conclusive non invasive early diagnostic testMultiple concerns exist regarding the unapproved use of CAa diagnostic test for GI malignanciesto help diagnose PCThese include its non specificityelevation in benign diseasesand absence inof the African American populationwhich underscore the need for new diagnostic tests prognostic markers for GI malignanciesespecially one that can confirm PC earlyA widely distributable technologywith a highly specific and sensitive diagnostic ability to discriminate real diseaseresectable neoplasmsfrom confounding high risk groupspancreatitisbenign pathologiesacute biliary obstructioncommon bile duct stonecholecithiasisand non malignant benign cystic neoplasmsserous pancreatic cystic neoplasmscould change the fate of PC patientsA vast series of cell linegenome wideand tissue based studies have elucidated differential expression of MUC AC and MUCin PC in comparison to pancreatitis and various benign pathologiesHoweverthe complexity of their structure and low serum levels limited their development as diagnostic markers for pancreatic cancerIn our preliminary studieswe developed an immunoassay to detect these markers and validated their diagnostic potential in a panel of patient serum samplesThese mucins emerged as highly sensitive and specific biomarkers for differentiating pancreatic cancer cases from controlsMUC AC efficiently differentiated early pancreatic cancer from healthy controlssensitiveSNspecificSPor benignSN SPand chronic pancreatitisSN SPgroupsFurthera CAand MUC AC combination significantlyandltimproved the diagnostic accuracy of CAin differentiating resectable cases from controlsTogether CAMUC AC and MUCdifferentiated PC cancer from controls with absolute specificityBased on preliminary evidencewe hypothesize that the mucin core proteinsMUC AC and MUCin combination with CAcreate a PC specific biomarker panel for early detection of pancreatic cancerDevelopment of the non invasive test for reproducible and economical detection of PC in the at risk population will enable early diagnosis for PC treatmentTo test this hypothesiswe propose to optimizeCAMUC ACand MUCmeasurement with a master calibrator that contains the analytesClinical validation will be performed using a blinded serum reference set from Early Detection Research Network that includes cases from the highrisk groupsOverallthe successful SBIR Fast track project would result in a commercial grade PC specific test that would improve upon CAfor early detection and diagnosis of pancreatic cancer Project Narrative Pancreatic CancerPCis a lethal malignancy lacking early diagnostic and prognostic markersThe present project harnesses the diagnostic ability of cancer antigen CAand potential of PC specific circulating mucins MUC ACMUCto discriminate and detect PCThe developednon invasive test is highly specific and sensitiveand can detect PC earlier in the at risk population to enable early diagnosis as a possible venue for PC treatment