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Antonio Irigoyen, Cristina Jimenez-Luna, Manuel Benavides, Octavio Caba, Javier Gallego, Francisco Manuel Ortuño, Carmen Guillen-Ponce, Ignacio Rojas, Enrique Aranda, Carolina Torres, Jose Prados
Integrative multi-platform meta-analysis of gene expression profiles in pancreatic ductal adenocarcinoma patients for identifying novel diagnostic biomarkers
www.plosone.org
www.plosone.org
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(Mar,)Tj
2.143 0 Td
(Hospital)Tj
3.617 0 Td
(Germans)Tj
3.8947 0 Td
(Trias)Tj
2.2621 0 Td
(i)Tj
0.4875 0 Td
(Pujol,)Tj
2.5455 0 Td
(Complejo)Tj
4.1613 0 Td
(Hospitalario)Tj
-32.5075 -1.3039 Td
(de)Tj
1.1678 0 Td
(Navarra,)Tj
3.685 0 Td
(Hospital)Tj
3.617 0 Td
(Reina)Tj
2.5115 0 Td
(Sofia,)Tj
2.4208 0 Td
(Hospital)Tj
3.617 0 Td
(General)Tj
3.3845 0 Td
(de)Tj
1.1679 0 Td
(Valencia,)Tj
3.9174 0 Td
(Hospital)Tj
3.617 0 Td
(Sant)Tj
1.9786 0 Td
(Pau,)Tj
1.9672 0 Td
(Hospital)Tj
-33.0517 -1.2982 Td
(Virgen)Tj
2.9876 0 Td
(de)Tj
1.1736 0 Td
(la)Tj
0.9014 0 Td
(Salud,)Tj
2.6532 0 Td
(Hospital)Tj
3.617 0 Td
(Parc)Tj
2.0126 0 Td
(Taul)Tj
0 Tc
1.7574 0.051 Td
()Tj
-0.004 Tc
0.3289 -0.051 Td
(,)Tj
0.4422 0 Td
(Hospital)Tj
3.617 0 Td
(Universitario)Tj
5.5275 0 Td
(Ramo)Tj
0 Tc
1.9389 0.051 Td
()Tj
-0.004 Tc
0.4478 -0.051 Td
(n)Tj
0.7654 0 Td
(y)Tj
0.6746 0 Td
(Cajal,)Tj
2.4775 0 Td
(Hospital)Tj
3.6226 0 Td
(Carlos)Tj
-34.9452 -1.2983 Td
(Haya,)Tj
2.5341 0 Td
(Hospital)Tj
3.617 0 Td
(Universitario)Tj
5.5275 0 Td
(Marques)Tj
3.7361 0 Td
(de)Tj
1.1735 0 Td
(Valdecilla,)Tj
4.388 0 Td
(Hospital)Tj
3.617 0 Td
(General)Tj
3.3845 0 Td
(de)Tj
1.1736 0 Td
(Elche,)Tj
2.6305 0 Td
(Hospital)Tj
3.6227 0 Td
(Son)Tj
-35.4045 -1.2983 Td
(Llatzer,)Tj
3.1691 0 Td
(Hospital)Tj
3.6169 0 Td
(Universitario)Tj
5.5276 0 Td
(de)Tj
1.1735 0 Td
(Donostia,)Tj
4.1046 0 Td
(and)Tj
1.7291 0 Td
(Hospital)Tj
3.617 0 Td
(Virgen)Tj
2.9933 0 Td
(de)Tj
1.1679 0 Td
(las)Tj
1.2642 0 Td
(Nieves.)Tj
-27.167 -1.3039 Td
(The)Tj
1.7858 0 Td
(54)Tj
1.1678 0 Td
(patients)Tj
3.3733 0 Td
(with)Tj
1.9955 0 Td
(unresectable)Tj
5.2044 0 Td
(PDAC)Tj
2.863 0 Td
(recruited)Tj
3.8551 0 Td
(in)Tj
1.0374 0 Td
(this)Tj
1.6725 0 Td
(study)Tj
2.3924 0 Td
(were)Tj
2.1203 0 Td
(divided)Tj
3.2145 0 Td
(into)Tj
1.8425 0 Td
(two)Tj
1.7121 0 Td
(inde-)Tj
-35.4328 -1.2982 Td
(pendent)Tj
3.5035 0 Td
(cohorts.)Tj
3.4413 0 Td
(Samples)Tj
3.4979 0 Td
(from)Tj
2.2054 0 Td
(cohort)Tj
2.8573 0 Td
(1,)Tj
0.9184 0 Td
(selected)Tj
3.3505 0 Td
(from)Tj
2.2054 0 Td
(our)Tj
1.627 0 Td
(previous)Tj
3.651 0 Td
(study)Tj
2.3868 0 Td
([)Tj
0.83 0.64 0.02 0 k
(22)Tj
0 g
(],)Tj
2.0749 0 Td
(include)Tj
3.1862 0 Td
(18)Tj
-34.9056 -1.2983 Td
(patients)Tj
3.3675 0 Td
(with)Tj
1.9956 0 Td
(PDAC)Tj
2.8629 0 Td
(recruited)Tj
3.8551 0 Td
(from)Tj
2.2054 0 Td
(January)Tj
3.3222 0 Td
(2009)Tj
2.1203 0 Td
(to)Tj
1.0261 0 Td
(July)Tj
1.7801 0 Td
(2012)Tj
2.1203 0 Td
(at)Tj
0.9525 0 Td
(the)Tj
1.4683 0 Td
(Virgen)Tj
2.9934 0 Td
(de)Tj
1.1678 0 Td
(las)Tj
1.2643 0 Td
(Nieves)Tj
2.8856 0 Td
(Uni-)Tj
-35.3874 -1.3039 Td
(versity)Tj
2.8516 0 Td
(Hospital)Tj
3.617 0 Td
(in)Tj
1.0374 0 Td
(Granada.)Tj
3.9062 0 Td
(Cohort)Tj
3.0954 0 Td
(2)Tj
0.6973 0 Td
(was)Tj
1.7008 0 Td
(also)Tj
1.7631 0 Td
(independent)Tj
5.2781 0 Td
(and)Tj
1.7291 0 Td
(included)Tj
3.7134 0 Td
(36)Tj
1.1678 0 Td
(new)Tj
1.8766 0 Td
(patients)Tj
3.3675 0 Td
(with)Tj
-35.8013 -1.2983 Td
(PDAC,)Tj
3.084 0 Td
(from)Tj
2.211 0 Td
(a)Tj
0.652 0 Td
(phase)Tj
2.4831 0 Td
(2)Tj
0.6974 0 Td
(randomized)Tj
5.0569 0 Td
(trial,)Tj
2.0636 0 Td
(recruited)Tj
3.8551 0 Td
(from)Tj
2.2054 0 Td
(March)Tj
2.8686 0 Td
(2012)Tj
2.1203 0 Td
(to)Tj
1.0262 0 Td
(February)Tj
3.838 0 Td
(2013)Tj
2.1203 0 Td
(from)Tj
2.211 0 Td
(15)Tj
-36.4929 -1.2983 Td
(different)Tj
3.6566 0 Td
(hospitals)Tj
3.7361 0 Td
(mediated)Tj
3.9458 0 Td
(by)Tj
1.1792 0 Td
(the)Tj
1.4683 0 Td
(Spanish)Tj
3.3505 0 Td
(cooperative)Tj
4.8472 0 Td
(group)Tj
2.6079 0 Td
(for)Tj
1.389 0 Td
(gastrointestinal)Tj
6.3495 0 Td
(tumor)Tj
2.744 0 Td
(ther-)Tj
-35.2741 -1.3039 Td
(apy)Tj
1.627 0 Td
(\(TTD\).)Tj
3.0841 0 Td
(The)Tj
1.7801 0 Td
(diagnosis)Tj
3.9572 0 Td
(of)Tj
1.0148 0 Td
(PDAC)Tj
2.863 0 Td
(was)Tj
1.7007 0 Td
(based)Tj
2.4718 0 Td
(on)Tj
1.2756 0 Td
(clinical)Tj
3.0784 0 Td
(evaluation)Tj
4.3597 0 Td
(and)Tj
1.7291 0 Td
(imaging)Tj
3.4866 0 Td
(studies,)Tj
-32.4281 -1.2982 Td
(which)Tj
2.6475 0 Td
(were)Tj
2.126 0 Td
(histologically)Tj
5.4708 0 Td
(confirmed)Tj
4.3937 0 Td
(by)Tj
1.1848 0 Td
(surgery)Tj
3.1918 0 Td
(or)Tj
1.0999 0 Td
(imaging-guided)Tj
6.5763 0 Td
(biopsy.)Tj
3.0557 0 Td
(The)Tj
1.7858 0 Td
(same)Tj
2.2564 0 Td
(enrol-)Tj
-33.7887 -1.2983 Td
(ment)Tj
2.3073 0 Td
(criteria)Tj
3.0784 0 Td
(were)Tj
2.1203 0 Td
(applied)Tj
3.1522 0 Td
(to)Tj
1.0261 0 Td
(both)Tj
2.0636 0 Td
(cohorts.)Tj
3.4412 0 Td
(Finally,)Tj
3.1691 0 Td
(18)Tj
1.1679 0 Td
(gender-,)Tj
3.5603 0 Td
(age-,)Tj
2.1146 0 Td
(and)Tj
1.7292 0 Td
(habit-)Tj
2.6078 0 Td
(matched)Tj
-31.538 -1.3039 Td
(healthy)Tj
3.1294 0 Td
(controls)Tj
3.4866 0 Td
(were)Tj
2.1203 0 Td
(included.)Tj
3.9401 0 Td
(The)Tj
1.7802 0 Td
(study)Tj
2.3867 0 Td
(was)Tj
1.7008 0 Td
(approved)Tj
3.9741 0 Td
(by)Tj
1.1792 0 Td
(the)Tj
1.474 0 Td
(Ethics)Tj
2.6646 0 Td
(Committee)Tj
4.7395 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(differ-)Tj
-35.0586 -1.2983 Td
(ent)Tj
1.491 0 Td
(hospitals,)Tj
3.9628 0 Td
(and)Tj
1.7291 0 Td
(all)Tj
1.1452 0 Td
(clinical)Tj
3.0784 0 Td
(investigations)Tj
5.7203 0 Td
(were)Tj
2.1259 0 Td
(conducted)Tj
4.4277 0 Td
(according)Tj
4.1839 0 Td
(to)Tj
1.0262 0 Td
(the)Tj
1.4683 0 Td
(principles)Tj
-30.3588 -1.2982 Td
(expressed)Tj
4.0932 0 Td
(in)Tj
1.0374 0 Td
(the)Tj
1.4684 0 Td
(Declaration)Tj
4.9095 0 Td
(of)Tj
1.0148 0 Td
(Helsinki.)Tj
3.8211 0 Td
(Written)Tj
3.3959 0 Td
(informed)Tj
3.9685 0 Td
(consent)Tj
3.3335 0 Td
(was)Tj
1.7008 0 Td
(obtained)Tj
3.7303 0 Td
(from)Tj
2.2054 0 Td
(all)Tj
-34.6788 -1.2983 Td
(patients)Tj
3.3675 0 Td
(and)Tj
1.7291 0 Td
(controls)Tj
3.4809 0 Td
(before)Tj
2.744 0 Td
(their)Tj
2.1089 0 Td
(enrolment)Tj
4.405 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(study.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 457.6818 cm
BT
/F12 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Blood)Tj
2.7118 0 Td
(collection)Tj
4.2756 0 Td
(and)Tj
1.7906 0 Td
(isolation)Tj
3.8551 0 Td
(of)Tj
1.0677 0 Td
(total)Tj
2.1591 0 Td
(RNA)Tj
2.3103 0 Td
(from)Tj
2.3102 0 Td
(PBMCs)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 440.674 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Prior)Tj
2.296 0 Td
(to)Tj
1.0261 0 Td
(any)Tj
1.6555 0 Td
(chemotherapy)Tj
5.947 0 Td
(regimen,)Tj
3.7644 0 Td
(peripheral)Tj
4.32 0 Td
(blood)Tj
2.5171 0 Td
(samples)Tj
3.3789 0 Td
(\(12)Tj
1.5137 0 Td
(ml\))Tj
1.6271 0 Td
(from)Tj
2.2053 0 Td
(all)Tj
1.1452 0 Td
(patients)Tj
3.3675 0 Td
(and)Tj
-34.7638 -1.2982 Td
(healthy)Tj
3.1294 0 Td
(controls)Tj
3.4866 0 Td
(were)Tj
2.1203 0 Td
(collected)Tj
3.7417 0 Td
(in)Tj
1.0318 0 Td
(PAXgene)Tj
3.9798 0 Td
(Blood)Tj
2.5852 0 Td
(RNA)Tj
2.262 0 Td
(Tubes)Tj
2.6532 0 Td
(\(PreAnalytix\))Tj
5.6523 0 Td
(and)Tj
1.7291 0 Td
(stored)Tj
2.7099 0 Td
(at)Tj
-35.0813 -1.2983 Td
(room)Tj
2.4207 0 Td
(temperature)Tj
5.1307 0 Td
(for)Tj
1.389 0 Td
(24)Tj
1.1678 0 Td
(hours,)Tj
2.744 0 Td
(to)Tj
1.0204 0 Td
(achieve)Tj
3.1748 0 Td
(complete)Tj
3.8778 0 Td
(lysis)Tj
1.9105 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(blood)Tj
2.5115 0 Td
(cells)Tj
1.9219 0 Td
(and)Tj
1.7291 0 Td
(immediate)Tj
4.5014 0 Td
(and)Tj
-35.9884 -1.2982 Td
(persistent)Tj
4.0875 0 Td
(RNA)Tj
2.262 0 Td
(stabilization.)Tj
5.2951 0 Td
(The)Tj
1.7801 0 Td
(RNA)Tj
2.2621 0 Td
(from)Tj
2.2053 0 Td
(PBMCs)Tj
3.2769 0 Td
(was)Tj
1.7007 0 Td
(isolated)Tj
3.2825 0 Td
(using)Tj
2.3925 0 Td
(the)Tj
1.4683 0 Td
(PAXgene)Tj
3.9798 0 Td
(Blood)Tj
-33.9928 -1.304 Td
(RNA)Tj
2.262 0 Td
(Kit)Tj
1.457 0 Td
(\(PreAnalytix\))Tj
5.6522 0 Td
(according)Tj
4.1896 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.4684 0 Td
(manufacturer's)Tj
6.2645 0 Td
(instructions.)Tj
5.2214 0 Td
(The)Tj
1.7858 0 Td
(final)Tj
2.0013 0 Td
(concentration)Tj
-31.3283 -1.2982 Td
(of)Tj
1.0147 0 Td
(purified)Tj
3.4073 0 Td
(RNA)Tj
2.262 0 Td
(was)Tj
1.7008 0 Td
(quantified)Tj
4.3086 0 Td
(by)Tj
1.1792 0 Td
(absorbance)Tj
4.7395 0 Td
(at)Tj
0.9525 0 Td
(260)Tj
1.644 0 Td
(nm)Tj
1.5874 0 Td
(in)Tj
1.0375 0 Td
(a)Tj
0.652 0 Td
(NanoDrop)Tj
4.5807 0 Td
(2000c)Tj
2.5455 0 Td
(spectropho-)Tj
-31.6117 -1.2983 Td
(tometer)Tj
3.3618 0 Td
(\(Thermo)Tj
3.8211 0 Td
(Scientific\).)Tj
4.4674 0 Td
(The)Tj
1.7801 0 Td
(quality)Tj
2.9537 0 Td
(was)Tj
1.7008 0 Td
(determined)Tj
4.8529 0 Td
(using)Tj
2.3867 0 Td
(the)Tj
1.4684 0 Td
(2100)Tj
2.1259 0 Td
(Bioanalyzer)Tj
4.8983 0 Td
(\(Agilent)Tj
-33.8171 -1.3039 Td
(Technologies\).)Tj
6.0944 0 Td
(All)Tj
1.4003 0 Td
(samples)Tj
3.3789 0 Td
(presented)Tj
4.1159 0 Td
(an)Tj
1.2018 0 Td
(RNA)Tj
2.2621 0 Td
(integrity)Tj
3.617 0 Td
(number)Tj
3.4129 0 Td
(\(RIN\))Tj
/F13 1 Tf
0 Tc
2.6021 0 Td
(>)Tj
/F7 1 Tf
-0.004 Tc
(7.0)Tj
2.1657 0 Td
(and)Tj
1.7291 0 Td
(a)Tj
0.6577 0 Td
(28S:18S)Tj
-32.6379 -1.2983 Td
(rRNA)Tj
2.6305 0 Td
(ratio)Tj
/F13 1 Tf
0 Tc
2.0976 0 Td
(>)Tj
/F7 1 Tf
-0.004 Tc
(1.0.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 308.0125 cm
BT
/F12 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(cDNA)Tj
2.8393 0 Td
(microarray)Tj
4.8898 0 Td
(analysis)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 291.0047 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Whole)Tj
2.8913 0 Td
(genome)Tj
3.4072 0 Td
(cDNA)Tj
2.7949 0 Td
(microarray)Tj
4.6772 0 Td
(hybridization)Tj
5.6125 0 Td
(of)Tj
1.0148 0 Td
(samples)Tj
3.3789 0 Td
(was)Tj
1.7008 0 Td
(performed)Tj
4.4674 0 Td
(using)Tj
2.3924 0 Td
(two)Tj
1.7064 0 Td
(different)Tj
-34.0438 -1.2982 Td
(platforms)Tj
4.0591 0 Td
(to)Tj
1.0262 0 Td
(identify)Tj
3.2938 0 Td
(potential)Tj
3.7644 0 Td
(PDAC)Tj
2.863 0 Td
(markers.)Tj
3.719 0 Td
(Affymetrix)Tj
4.5808 0 Td
(microarray-based)Tj
7.2793 0 Td
(gene)Tj
2.0806 0 Td
(expression)Tj
-32.6662 -1.3039 Td
(profiling)Tj
3.6963 0 Td
(was)Tj
1.7008 0 Td
(carried)Tj
3.0387 0 Td
(out)Tj
1.5534 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.4683 0 Td
(samples)Tj
3.3789 0 Td
(from)Tj
2.211 0 Td
(the)Tj
1.4683 0 Td
(patients)Tj
3.3676 0 Td
(included)Tj
3.7133 0 Td
(in)Tj
1.0318 0 Td
(Cohort)Tj
3.0954 0 Td
(1)Tj
0.6974 0 Td
(and)Tj
1.7291 0 Td
(18)Tj
1.1735 0 Td
(healthy)Tj
-34.5994 -1.2983 Td
(controls,)Tj
3.7076 0 Td
(using)Tj
2.3868 0 Td
(GeneChip)Tj
/F14 1 Tf
(1)Tj
/F7 1 Tf
5.3064 0 Td
(Human)Tj
3.3165 0 Td
(Gene)Tj
2.3301 0 Td
(ST)Tj
1.3096 0 Td
(1.0)Tj
1.3946 0 Td
(Arrays)Tj
2.897 0 Td
(\(Affymetrix)Tj
4.9209 0 Td
(Inc.\))Tj
2.0977 0 Td
(according)Tj
4.1839 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
-34.8772 -1.2983 Td
(recommended)Tj
6.032 0 Td
(protocol.)Tj
3.8268 0 Td
(Briefly,)Tj
3.0727 0 Td
(l)Tj
/F15 1 Tf
0.4706 0 Td
[()]TJ
/F7 1 Tf
(g)Tj
1.1905 0 Td
(of)Tj
1.0148 0 Td
(high-quality)Tj
5.091 0 Td
(total)Tj
2.0069 0 Td
(RNA)Tj
2.2621 0 Td
(was)Tj
1.6951 0 Td
(used)Tj
2.0636 0 Td
(to)Tj
1.0261 0 Td
(synthesize)Tj
4.2973 0 Td
(double-)Tj
-34.0495 -1.3039 Td
(stranded)Tj
3.7133 0 Td
(cDNA,)Tj
3.0217 0 Td
(and)Tj
1.7291 0 Td
(biotin-tagged)Tj
5.5843 0 Td
(cRNA)Tj
2.6815 0 Td
(was)Tj
1.7008 0 Td
(produced.)Tj
4.2689 0 Td
(This)Tj
1.99 0 Td
(cRNA)Tj
2.6872 0 Td
(was)Tj
1.6951 0 Td
(recovered,)Tj
4.371 0 Td
(purified)Tj
-33.4429 -1.2982 Td
(and)Tj
1.7291 0 Td
(then)Tj
2.0182 0 Td
(hybridized)Tj
4.5071 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.4684 0 Td
(chips)Tj
2.3187 0 Td
(overnight)Tj
4.0818 0 Td
(at)Tj
0.9525 0 Td
(45C.)Tj
2.4491 0 Td
(After)Tj
2.2904 0 Td
(being)Tj
2.4264 0 Td
(washed)Tj
3.1805 0 Td
(and)Tj
1.7291 0 Td
(stained,)Tj
3.3052 0 Td
(the)Tj
1.4683 0 Td
(arrays)Tj
-34.9509 -1.2983 Td
(were)Tj
2.1203 0 Td
(scanned)Tj
3.4865 0 Td
(with)Tj
2.0013 0 Td
(a)Tj
0.652 0 Td
(GeneChip)Tj
4.3029 0 Td
(Scanner)Tj
3.4469 0 Td
(3000)Tj
2.126 0 Td
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