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Principal Investigator
Oliver John Semmes
Awardee Organization

Eastern Virginia Medical School
United States

Fiscal Year
2021
Activity Code
U01
Project End Date
NIH RePORTER
For more information, see NIH RePORTER Project 3U01CA214194-05S2

Development of Protein Biomarkers in Post-DRE Urine for use in Liquid Biopsy of Prostate Cancer

Prostate cancer (PCa) remains the most common non-skin malignancy afflicting men in the United states. It is the second leading cause of cancer-related death. The clinical diversity of PCa is dramatic, ranging from asymptomatic disease to metastatic and fatal malignancy. One cause of this clinical diversity is the remarkable intra- and inter-tumoural heterogeneity in disease genomics. As a result, currently clinically-used risk-stratification strategies do not robustly discriminate aggressive from indolent diseases, leading to systemic over- and undertreatment. Approximately 40% of men diagnosed with PCa who seek curative treatment undergo surgical removal of their prostate (radical prostatectomy, RP). Of these, approximately 30% are found at surgery to have disease outside their prostate (non-organ-confined, non-OC). These men are candidates for multi-modal adjuvant treatment with chemo- and hormonetherapy to improve outcomes. We therefore propose to tackle this problem, using fluid biomarkers to circumvent the molecular heterogeneity of the disease. Our proposal leverages an active and productive multi-investigator, multi-institutional proteomic collaboration to develop biomarkers for the early detection of locally aggressive non-organ-confined disease. Our two lead biomarkers are 1) A multiple peptide panel that discriminates OC from non-OC in EDRN phase 2 equivalent validation (Nature Communications, in press). 2) Surface expression of CUB Domain Containing Protein 1 on exosomes differentiates PCa aggressiveness (EDRN Phase 1 equivalent discovery, Oncotarget, 2016). We propose both validation of these targets in a globally-unique biobank of expressed prostatic secretions, as well as novel biomarker discovery/development strategies to extend them in the same clinical context and sample matrix. Successful completion of our proposed studies will result in validation of at least two biomarkers for clinical utility in separation of OC vs. non-OC disease, helping to personalize therapy for a tumour type that afflicts 1 in 7 North American men.

Publications

  • Zeltser N, Zhu C, Oh J, Li CH, Boutros PC. Sex Differences in Cancer Functional Genomics: Gene Dependency and Drug Sensitivity. bioRxiv : the preprint server for biology. 2025 Mar 21. PMID: 39975298
  • Liss MA, Zeltser N, Zheng Y, Lopez C, Liu M, Patel Y, Yamaguchi TN, Eng SE, Tian M, Semmes OJ, Lin DW, Brooks JD, Wei JT, Klein EA, Tewari AK, Mosquera JM, Khani F, Robinson BD, Aasad M, Troyer DA, Kagan J, Sanda MG, Thompson IM, Boutros PC, Leach RJ. Upgrading of Grade Group 1 Prostate Cancer at Prostatectomy: Germline Risk Factors in a Prospective Cohort. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2024 Nov 1;33(11):1500-1511. PMID: 39158404
  • Li CH, Prokopec SD, Sun RX, Yousif F, Schmitz N, PCAWG Tumour Subtypes and Clinical Translation, Boutros PC, PCAWG Consortium, Al-Shahrour F, Atwal G, Bailey PJ, Biankin AV, Boutros PC, Campbell PJ, Chang DK, Cooke SL, Deshpande V, Faltas BM, Faquin WC, Garraway L, Getz G, Grimmond SM, Haider S, Hoadley KA, Jiao W, Kaiser VB, Karlić R, Kato M, Kübler K, Lazar AJ, Li CH, Louis DN, Margolin A, Martin S, Nahal-Bose HK, Nielsen GP, Nik-Zainal S, Omberg L, P'ng C, Perry MD, Polak P, Rheinbay E, Rubin MA, Semple CA, Sgroi DC, Shibata T, Siebert R, Smith J, Stein LD, Stobbe MD, Sun RX, Thai K, Wright DW, Wu CL, Yuan K, Zhang J, Aaltonen LA, Abascal F, Abeshouse A, Aburatani H, Adams DJ, Agrawal N, Ahn KS, Ahn SM, Aikata H, Akbani R, Akdemir KC, Al-Ahmadie H, Al-Sedairy ST, Al-Shahrour F, Alawi M, Albert M, Aldape K, Alexandrov LB, Ally A, Alsop K, Alvarez EG, Amary F, Amin SB, Aminou B, Ammerpohl O, Anderson MJ, Ang Y, Antonello D, Anur P, Aparicio S, Appelbaum EL, Arai Y, Aretz A, Arihiro K, Ariizumi SI, Armenia J, Arnould L, Asa S, Assenov Y, Atwal G, Aukema S, Auman JT, Aure MR, Awadalla P, Aymerich M, Bader GD, Baez-Ortega A, Bailey MH, Bailey PJ, Balasundaram M, Balu S, Bandopadhayay P, Banks RE, Barbi S, Barbour AP, Barenboim J, Barnholtz-Sloan J, Barr H, Barrera E, Bartlett J, Bartolome J, Bassi C, Bathe OF, Baumhoer D, Bavi P, Baylin SB, Bazant W, Beardsmore D, Beck TA, Behjati S, Behren A, Niu B, Bell C, Beltran S, Benz C, Berchuck A, Bergmann AK, Bergstrom EN, Berman BP, Berney DM, Bernhart SH, Beroukhim R, Berrios M, Bersani S, Bertl J, Betancourt M, Bhandari V, Bhosle SG, Biankin AV, Bieg M, Bigner D, Binder H, Birney E, Birrer M, Biswas NK, Bjerkehagen B, Bodenheimer T, Boice L, Bonizzato G, De Bono JS, Boot A, Bootwalla MS, Borg A, Borkhardt A, Boroevich KA, Borozan I, Borst C, Bosenberg M, Bosio M, Boultwood J, Bourque G, Boutros PC, Bova GS, Bowen DT, Bowlby R, Bowtell DDL, Boyault S, Boyce R, Boyd J, Brazma A, Brennan P, Brewer DS, Brinkman AB, Bristow RG, Broaddus RR, Brock JE, Brock M, Broeks A, Brooks AN, Brooks D, Brors B, Brunak S, Bruxner TJC, Bruzos AL, Buchanan A, Buchhalter I, Buchholz C, Bullman S, Burke H, Burkhardt B, Burns KH, Busanovich J, Bustamante CD, Butler AP, Butte AJ, Byrne NJ, Børresen-Dale AL, Caesar-Johnson SJ, Cafferkey A, Cahill D, Calabrese C, Caldas C, Calvo F, Camacho N, Campbell PJ, Campo E, Cantù C, Cao S, Carey TE, Carlevaro-Fita J, Carlsen R, Cataldo I, Cazzola M, Cebon J, Cerfolio R, Chadwick DE, Chakravarty D, Chalmers D, Chan CWY, Chan K, Chan-Seng-Yue M, Chandan VS, Chang DK, Chanock SJ, Chantrill LA, Chateigner A, Chatterjee N, Chayama K, Chen HW, Chen J, Chen K, Chen Y, Chen Z, Cherniack AD, Chien J, Chiew YE, Chin SF, Cho J, Cho S, Choi JK, Choi W, Chomienne C, Chong Z, Choo SP, Chou A, Christ AN, Christie EL, Chuah E, Cibulskis C, Cibulskis K, Cingarlini S, Clapham P, Claviez A, Cleary S, Cloonan N, Cmero M, Collins CC, Connor AA, Cooke SL, Cooper CS, Cope L, Corbo V, Cordes MG, Cordner SM, Cortés-Ciriano I, Covington K, Cowin PA, Craft B, Craft D, Creighton CJ, Cun Y, Curley E, Cutcutache I, Czajka K, Czerniak B, Dagg RA, Danilova L, Davi MV, Davidson NR, Davies H, Davis IJ, Davis-Dusenbery BN, Dawson KJ, De La Vega FM, De Paoli-Iseppi R, Defreitas T, Dei Tos AP, Delaneau O, Demchok JA, Demeulemeester J, Demidov GM, Demircioğlu D, Dennis NM, Denroche RE, Dentro SC, Desai N, Deshpande V, Deshwar AG, Desmedt C, Deu-Pons J, Dhalla N, Dhani NC, Dhingra P, Dhir R, DiBiase A, Diamanti K, Ding L, Ding S, Dinh HQ, Dirix L, Doddapaneni H, Donmez N, Dow MT, Drapkin R, Drechsel O, Drews RM, Serge S, Dudderidge T, Dueso-Barroso A, Dunford AJ, Dunn M, Dursi LJ, Duthie FR, Dutton-Regester K, Eagles J, Easton DF, Edmonds S, Edwards PA, Edwards SE, Eeles RA, Ehinger A, Eils J, Eils R, El-Naggar A, Eldridge M, Ellrott K, Erkek S, Escaramis G, Espiritu SMG, Estivill X, Etemadmoghadam D, Eyfjord JE, Faltas BM, Fan D, Fan Y, Faquin WC, Farcas C, Fassan M, Fatima A, Favero F, Fayzullaev N, Felau I, Fereday S, Ferguson ML, Ferretti V, Feuerbach L, Field MA, Fink JL, Finocchiaro G, Fisher C, Fittall MW, Fitzgerald A, Fitzgerald RC, Flanagan AM, Fleshner NE, Flicek P, Foekens JA, Fong KM, Fonseca NA, Foster CS, Fox NS, Fraser M, Frazer S, Frenkel-Morgenstern M, Friedman W, Frigola J, Fronick CC, Fujimoto A, Fujita M, Fukayama M, Fulton LA, Fulton RS, Furuta M, Futreal PA, Füllgrabe A, Gabriel SB, Gallinger S, Gambacorti-Passerini C, Gao J, Gao S, Garraway L, Garred Ø, Garrison E, Garsed DW, Gehlenborg N, Gelpi JLL, George J, Gerhard DS, Gerhauser C, Gershenwald JE, Gerstein M, Gerstung M, Getz G, Ghori M, Ghossein R, Giama NH, Gibbs RA, Gill AJ, Gill P, Giri DD, Glodzik D, Gnanapragasam VJ, Goebler ME, Goldman MJ, Gomez C, Gonzalez S, Gonzalez-Perez A, Gordenin DA, Gossage J, Gotoh K, Govindan R, Grabau D, Graham JS, Grant RC, Green AR, Green E, Greger L, Grehan N, Grimaldi S, Grimmond SM, Grossman RL, Grundhoff A, Gundem G, Guo Q, Gupta M, Gupta S, Gut IG, Gut M, Göke J, Ha G, Haake A, Haan D, Haas S, Haase K, Haber JE, Habermann N, Hach F, Haider S, Hama N, Hamdy FC, Hamilton A, Hamilton MP, Han L, Hanna GB, Hansmann M, Haradhvala NJ, Harismendy O, Harliwong I, Harmanci AO, Harrington E, Hasegawa T, Haussler D, Hawkins S, Hayami S, Hayashi S, Hayes DN, Hayes SJ, Hayward NK, Hazell S, He Y, Heath AP, Heath SC, Hedley D, Hegde AM, Heiman DI, Heinold MC, Heins Z, Heisler LE, Hellstrom-Lindberg E, Helmy M, Heo SG, Hepperla AJ, Heredia-Genestar JM, Herrmann C, Hersey P, Hess JM, Hilmarsdottir H, Hinton J, Hirano S, Hiraoka N, Hoadley KA, Hobolth A, Hodzic E, Hoell JI, Hoffmann S, Hofmann O, Holbrook A, Holik AZ, Hollingsworth MA, Holmes O, Holt RA, Hong C, Hong EP, Hong JH, Hooijer GK, Hornshøj H, Hosoda F, Hou Y, Hovestadt V, Howat W, Hoyle AP, Hruban RH, Hu J, Hu T, Hua X, Huang KL, Huang M, Huang MN, Huang V, Huang Y, Huber W, Hudson TJ, Hummel M, Hung JA, Huntsman D, Hupp TR, Huse J, Huska MR, Hutter B, Hutter CM, Hübschmann D, Iacobuzio-Donahue CA, Imbusch CD, Imielinski M, Imoto S, Isaacs WB, Isaev K, Ishikawa S, Iskar M, Islam SMA, Ittmann M, Ivkovic S, Izarzugaza JMG, Jacquemier J, Jakrot V, Jamieson NB, Jang GH, Jang SJ, Jayaseelan JC, Jayasinghe R, Jefferys SR, Jegalian K, Jennings JL, Jeon SH, Jerman L, Ji Y, Jiao W, Johansson PA, Johns AL, Johns J, Johnson R, Johnson TA, Jolly C, Joly Y, Jonasson JG, Jones CD, Jones DR, Jones DTW, Jones N, Jones SJM, Jonkers J, Ju YS, Juhl H, Jung J, Juul M, Juul RI, Juul S, Jäger N, Kabbe R, Kahles A, Kahraman A, Kaiser VB, Kakavand H, Kalimuthu S, von Kalle C, Kang KJ, Karaszi K, Karlan B, Karlić R, Karsch D, Kasaian K, Kassahn KS, Katai H, Kato M, Katoh H, Kawakami Y, Kay JD, Kazakoff SH, Kazanov MD, Keays M, Kebebew E, Kefford RF, Kellis M, Kench JG, Kennedy CJ, Kerssemakers JNA, Khoo D, Khoo V, Khuntikeo N, Khurana E, Kilpinen H, Kim HK, Kim HL, Kim HY, Kim H, Kim J, Kim J, Kim JK, Kim Y, King TA, Klapper W, Kleinheinz K, Klimczak LJ, Knappskog S, Kneba M, Knoppers BM, Koh Y, Komorowski J, Komura D, Komura M, Kong G, Kool M, Korbel JO, Korchina V, Korshunov A, Koscher M, Koster R, Kote-Jarai Z, Koures A, Kovacevic M, Kremeyer B, Kretzmer H, Kreuz M, Krishnamurthy S, Kube D, Kumar K, Kumar P, Kumar S, Kumar Y, Kundra R, Kübler K, Küppers R, Lagergren J, Lai PH, Laird PW, Lakhani SR, Lalansingh CM, Lalonde E, Lamaze FC, Lambert A, Lander E, Landgraf P, Landoni L, Langerød A, Lanzós A, Larsimont D, Larsson E, Lathrop M, Lau LMS, Lawerenz C, Lawlor RT, Lawrence MS, Lazar AJ, Le X, Lee D, Lee D, Lee EA, Lee HJ, Lee JJ, Lee JY, Lee J, Lee MTM, Lee-Six H, Lehmann KV, Lehrach H, Lenze D, Leonard CR, Leongamornlert DA, Leshchiner I, Letourneau L, Letunic I, Levine DA, Lewis L, Ley T, Li C, Li CH, Li HI, Li J, Li L, Li S, Li S, Li X, Li X, Li X, Li Y, Liang H, Liang SB, Lichter P, Lin P, Lin Z, Linehan WM, Lingjærde OC, Liu D, Liu EM, Liu FF, Liu F, Liu J, Liu X, Livingstone J, Livitz D, Livni N, Lochovsky L, Loeffler M, Long GV, Lopez-Guillermo A, Lou S, Louis DN, Lovat LB, Lu Y, Lu YJ, Lu Y, Luchini C, Lungu I, Luo X, Luxton HJ, Lynch AG, Lype L, López C, López-Otín C, Ma EZ, Ma Y, MacGrogan G, MacRae S, Macintyre G, Madsen T, Maejima K, Mafficini A, Maglinte DT, Maitra A, Majumder PP, Malcovati L, Malikic S, Malleo G, Mann GJ, Mantovani-Löffler L, Marchal K, Marchegiani G, Mardis ER, Margolin AA, Marin MG, Markowetz F, Markowski J, Marks J, Marques-Bonet T, Marra MA, Marsden L, Martens JWM, Martin S, Martin-Subero JI, Martincorena I, Martinez-Fundichely A, Maruvka YE, Mashl RJ, Massie CE, Matthew TJ, Matthews L, Mayer E, Mayes S, Mayo M, Mbabaali F, McCune K, McDermott U, McGillivray PD, McLellan MD, McPherson JD, McPherson JR, McPherson TA, Meier SR, Meng A, Meng S, Menzies A, Merrett ND, Merson S, Meyerson M, Meyerson W, Mieczkowski PA, Mihaiescu GL, Mijalkovic S, Mijalkovic-Lazic AM, Mikkelsen T, Milella M, Mileshkin L, Miller CA, Miller DK, Miller JK, Mills GB, Milovanovic A, Minner S, Miotto M, Arnau GM, Mirabello L, Mitchell C, Mitchell TJ, Miyano S, Miyoshi N, Mizuno S, Molnár-Gábor F, Moore MJ, Moore RA, Morganella S, Morris QD, Morrison C, Mose LE, Moser CD, Muiños F, Mularoni L, Mungall AJ, Mungall K, Musgrove EA, Mustonen V, Mutch D, Muyas F, Muzny DM, Muñoz A, Myers J, Myklebost O, Möller P, Nagae G, Nagrial AM, Nahal-Bose HK, Nakagama H, Nakagawa H, Nakamura H, Nakamura T, Nakano K, Nandi T, Nangalia J, Nastic M, Navarro A, Navarro FCP, Neal DE, Nettekoven G, Newell F, Newhouse SJ, Newton Y, Ng AWT, Ng A, Nicholson J, Nicol D, Nie Y, Nielsen GP, Nielsen MM, Nik-Zainal S, Noble MS, Nones K, Northcott PA, Notta F, O'Connor BD, O'Donnell P, O'Donovan M, O'Meara S, O'Neill BP, O'Neill JR, Ocana D, Ochoa A, Oesper L, Ogden C, Ohdan H, Ohi K, Ohno-Machado L, Oien KA, Ojesina AI, Ojima H, Okusaka T, Omberg L, Ong CK, Ossowski S, Ott G, Ouellette BFF, P'ng C, Paczkowska M, Paiella S, Pairojkul C, Pajic M, Pan-Hammarström Q, Papaemmanuil E, Papatheodorou I, Paramasivam N, Park JW, Park JW, Park K, Park K, Park PJ, Parker JS, Parsons SL, Pass H, Pasternack D, Pastore A, Patch AM, Pauporté I, Pea A, Pearson JV, Pedamallu CS, Pedersen JS, Pederzoli P, Peifer M, Pennell NA, Perou CM, Perry MD, Petersen GM, Peto M, Petrelli N, Petryszak R, Pfister SM, Phillips M, Pich O, Pickett HA, Pihl TD, Pillay N, Pinder S, Pinese M, Pinho AV, Pitkänen E, Pivot X, Piñeiro-Yáñez E, Planko L, Plass C, Polak P, Pons T, Popescu I, Potapova O, Prasad A, Preston SR, Prinz M, Pritchard AL, Provenzano E, Puente XS, Puig S, Puiggròs M, Pulido-Tamayo S, Pupo GM, Purdie CA, Quinn MC, Rabionet R, Rader JS, Radlwimmer B, Radovic P, Raeder B, Raine KM, Ramakrishna M, Ramakrishnan K, Ramalingam S, Raphael BJ, Rathmell WK, Rausch T, Reifenberger G, Reimand J, Reis-Filho J, Reuter V, Reyes-Salazar I, Reyna MA, Reynolds SM, Rheinbay E, Riazalhosseini Y, Richardson AL, Richter J, Ringel M, Ringnér M, Rino Y, Rippe K, Roach J, Roberts LR, Roberts ND, Roberts SA, Robertson AG, Robertson AJ, Rodriguez JB, Rodriguez-Martin B, Rodríguez-González FG, Roehrl MHA, Rohde M, Rokutan H, Romieu G, Rooman I, Roques T, Rosebrock D, Rosenberg M, Rosenstiel PC, Rosenwald A, Rowe EW, Royo R, Rozen SG, Rubanova Y, Rubin MA, Rubio-Perez C, Rudneva VA, Rusev BC, Ruzzenente A, Rätsch G, Sabarinathan R, Sabelnykova VY, Sadeghi S, Sahinalp SC, Saini N, Saito-Adachi M, Saksena G, Salcedo A, Salgado R, Salichos L, Sallari R, Saller C, Salvia R, Sam M, Samra JS, Sanchez-Vega F, Sander C, Sanders G, Sarin R, Sarrafi I, Sasaki-Oku A, Sauer T, Sauter G, Saw RPM, Scardoni M, Scarlett CJ, Scarpa A, Scelo G, Schadendorf D, Schein JE, Schilhabel MB, Schlesner M, Schlomm T, Schmidt HK, Schramm SJ, Schreiber S, Schultz N, Schumacher SE, Schwarz RF, Scolyer RA, Scott D, Scully R, Seethala R, Segre AV, Selander I, Semple CA, Senbabaoglu Y, Sengupta S, Sereni E, Serra S, Sgroi DC, Shackleton M, Shah NC, Shahabi S, Shang CA, Shang P, Shapira O, Shelton T, Shen C, Shen H, Shepherd R, Shi R, Shi Y, Shiah YJ, Shibata T, Shih J, Shimizu E, Shimizu K, Shin SJ, Shiraishi Y, Shmaya T, Shmulevich I, Shorser SI, Short C, Shrestha R, Shringarpure SS, Shriver C, Shuai S, Sidiropoulos N, Siebert R, Sieuwerts AM, Sieverling L, Signoretti S, Sikora KO, Simbolo M, Simon R, Simons JV, Simpson JT, Simpson PT, Singer S, Sinnott-Armstrong N, Sipahimalani P, Skelly TJ, Smid M, Smith J, Smith-McCune K, Socci ND, Sofia HJ, Soloway MG, Song L, Sood AK, Sothi S, Sotiriou C, Soulette CM, Span PN, Spellman PT, Sperandio N, Spillane AJ, Spiro O, Spring J, Staaf J, Stadler PF, Staib P, Stark SG, Stebbings L, Stefánsson ÓA, Stegle O, Stein LD, Stenhouse A, Stewart C, Stilgenbauer S, Stobbe MD, Stratton MR, Stretch JR, Struck AJ, Stuart JM, Stunnenberg HG, Su H, Su X, Sun RX, Sungalee S, Susak H, Suzuki A, Sweep F, Szczepanowski M, Sültmann H, Yugawa T, Tam A, Tamborero D, Tan BKT, Tan D, Tan P, Tanaka H, Taniguchi H, Tanskanen TJ, Tarabichi M, Tarnuzzer R, Tarpey P, Taschuk ML, Tatsuno K, Tavaré S, Taylor DF, Taylor-Weiner A, Teague JW, Teh BT, Tembe V, Temes J, Thai K, Thayer SP, Thiessen N, Thomas G, Thomas S, Thompson A, Thompson AM, Thompson JF, Thompson RH, Thorne H, Thorne LB, Thorogood A, Tiao G, Tijanic N, Timms LE, Tirabosco R, Tojo M, Tommasi S, Toon CW, Toprak UH, Torrents D, Tortora G, Tost J, Totoki Y, Townend D, Traficante N, Treilleux I, Trotta JR, Trümper LHP, Tsao M, Tsunoda T, Tubio JMC, Tucker O, Turkington R, Turner DJ, Tutt A, Ueno M, Ueno NT, Umbricht C, Umer HM, Underwood TJ, Urban L, Urushidate T, Ushiku T, Uusküla-Reimand L, Valencia A, Van Den Berg DJ, Van Laere S, Van Loo P, Van Meir EG, Van den Eynden GG, Van der Kwast T, Vasudev N, Vazquez M, Vedururu R, Veluvolu U, Vembu S, Verbeke LPC, Vermeulen P, Verrill C, Viari A, Vicente D, Vicentini C, Raghavan KV, Viksna J, Vilain RE, Villasante I, Vincent-Salomon A, Visakorpi T, Voet D, Vyas P, Vázquez-García I, Waddell NM, Waddell N, Wadelius C, Wadi L, Wagener R, Wala JA, Wang J, Wang J, Wang L, Wang Q, Wang W, Wang Y, Wang Z, Waring 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