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Status |
Public on Oct 12, 2012 |
Title |
Biomarker discovery in non-small cell lung cancer: integrating gene expression profiling, meta-analysis and tissue microarray validation |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Background: Global gene expression profiling has been widely used in lung cancer research to identify clinically relevant molecular subtypes as well as to predict prognosis and therapy response. So far, the value of these multi-gene signatures in clinical practice is unclear and the biological importance of individual genes is difficult to assess as the published signatures virtually do not overlap.
Methods: Here we describe a novel single institute cohort, including 196 non-small lung cancer (NSCLC) cases with clinical information and long-term follow-up, which was used as a training set to screen for single genes with prognostic impact. The top 450 gene probe sets identified using a univariate Cox regression model (significance level p<0.01) were tested in a meta-analysis including five publicly available independent lung cancer cohorts (n=860).
Results: The meta-analysis revealed that 17 probe sets were significantly associated with survival (p<0.0005) with a false discovery rate of 1%. The prognostic impact of one of these genes, the cell adhesion molecule 1 (CADM1), was confirmed by use of immunohistochemistry on a tissue microarray including 355 NSCLC samples. Low CADM1 protein expression was associated with shorter survival (p=0.028), with particular influence in the adenocarcinoma patient subgroup (p=0.002).
Conclusions: We were able to validate single genes with independent prognostic impact using a novel NSCLC cohort together with a meta-analysis approach. CADM1 was identified as an immunohistochemical marker with a potential application in clinical diagnostics.
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Overall design |
Fresh frozen tissue of 196 consecutive NSCLC patients, operated between 1995 and 2005 were analyzed using Affymetrix microarrays HG-U133-Plus2. Clinical data were retrieved from the regional lung cancer registry.
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Contributor(s) |
Botling J, Edlund K, Lohr M, Hellwig B, Holmberg L, Lambe M, Berglund A, Ekman S, Bergkvist M, Pontén F, König A, Rahnenführer J, Hengstler JG, Micke P, Planck M |
Citation(s) |
23032747, 29112949, 26608184, 33576873, 35574381 |
Submission date |
May 03, 2012 |
Last update date |
May 26, 2022 |
Contact name |
Patrick Micke |
E-mail(s) |
patrick.micke@igp.uu.se
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Organization name |
Uppsala University
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Street address |
Rudbeck laboratory
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City |
Uppsala |
ZIP/Postal code |
75185 |
Country |
Sweden |
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Platforms (1) |
GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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Samples (196)
|
GSM1019141 |
Patient 13, male, squamous |
GSM1019142 |
Patient 14, male, squamous |
GSM1019143 |
Patient 19, female, adeno |
GSM1019144 |
Patient 22, male, adeno |
GSM1019145 |
Patient 23, female, adeno |
GSM1019146 |
Patient 27, female, squamous |
GSM1019147 |
Patient 32, male, adeno |
GSM1019148 |
Patient 33, male, large |
GSM1019149 |
Patient 35, female, adeno |
GSM1019150 |
Patient 37, female, adeno |
GSM1019151 |
Patient 39, female, squamous |
GSM1019152 |
Patient 48, female, adeno |
GSM1019153 |
Patient 61, male, adeno |
GSM1019154 |
Patient 81, male, adeno |
GSM1019155 |
Patient 87, female, large |
GSM1019156 |
Patient 88, male, squamous |
GSM1019157 |
Patient 98, male, squamous |
GSM1019158 |
Patient 112, male, adeno |
GSM1019159 |
Patient 131, female, squamous |
GSM1019160 |
Patient 133, female, adeno |
GSM1019161 |
Patient 158, male, large |
GSM1019162 |
Patient 162, male, adeno |
GSM1019163 |
Patient 165, male, adeno |
GSM1019164 |
Patient 169, female, adeno |
GSM1019165 |
Patient 171, male, adeno |
GSM1019166 |
Patient 172, female, adeno |
GSM1019167 |
Patient 174, male, large |
GSM1019168 |
Patient 175, male, squamous |
GSM1019169 |
Patient 189, female, adeno |
GSM1019170 |
Patient 192, male, adeno |
GSM1019171 |
Patient 193, female, adeno |
GSM1019172 |
Patient 195, male, squamous |
GSM1019173 |
Patient 196, male, large |
GSM1019174 |
Patient 197, male, adeno |
GSM1019175 |
Patient 200, male, adeno |
GSM1019176 |
Patient 201, female, adeno |
GSM1019177 |
Patient 202, male, squamous |
GSM1019178 |
Patient 203, male, large |
GSM1019179 |
Patient 207, male, large |
GSM1019180 |
Patient 212, male, adeno |
GSM1019181 |
Patient 213, female, adeno |
GSM1019182 |
Patient 214, male, large |
GSM1019183 |
Patient 215, female, adeno |
GSM1019184 |
Patient 217, female, squamous |
GSM1019185 |
Patient 223, male, adeno |
GSM1019186 |
Patient 224, female, adeno |
GSM1019187 |
Patient 228, female, adeno |
GSM1019188 |
Patient 229, female, adeno |
GSM1019189 |
Patient 234, male, large |
GSM1019190 |
Patient 235, female, adeno |
GSM1019191 |
Patient 243, male, squamous |
GSM1019192 |
Patient 247, female, adeno |
GSM1019193 |
Patient 249, male, squamous |
GSM1019194 |
Patient 255, female, adeno |
GSM1019195 |
Patient 256, female, squamous |
GSM1019196 |
Patient 258, male, adeno |
GSM1019197 |
Patient 260, male, adeno |
GSM1019198 |
Patient 265, male, squamous |
GSM1019199 |
Patient 271, female, squamous |
GSM1019200 |
Patient 272, female, adeno |
GSM1019201 |
Patient 274, male, squamous |
GSM1019202 |
Patient 278, male, squamous |
GSM1019203 |
Patient 282, female, adeno |
GSM1019204 |
Patient 284, male, adeno |
GSM1019205 |
Patient 288, male, adeno |
GSM1019206 |
Patient 291, female, squamous |
GSM1019207 |
Patient 292, female, adeno |
GSM1019208 |
Patient 295, female, large |
GSM1019209 |
Patient 296, female, squamous |
GSM1019210 |
Patient 297, male, adeno |
GSM1019211 |
Patient 299, female, adeno |
GSM1019212 |
Patient 300, female, squamous |
GSM1019213 |
Patient 301, male, adeno |
GSM1019214 |
Patient 302, female, adeno |
GSM1019215 |
Patient 305, male, squamous |
GSM1019216 |
Patient 309, female, adeno |
GSM1019217 |
Patient 310, female, adeno |
GSM1019218 |
Patient 311, male, adeno |
GSM1019219 |
Patient 314, male, large |
GSM1019220 |
Patient 317, female, adeno |
GSM1019221 |
Patient 319, male, squamous |
GSM1019222 |
Patient 331, male, large |
GSM1019223 |
Patient 332, male, large |
GSM1019224 |
Patient 338, female, adeno |
GSM1019225 |
Patient 341, female, adeno |
GSM1019226 |
Patient 342, male, squamous |
GSM1019227 |
Patient 344, female, squamous |
GSM1019228 |
Patient 347, male, adeno |
GSM1019229 |
Patient 357, male, squamous |
GSM1019230 |
Patient 359, female, adeno |
GSM1019231 |
Patient 361, male, large |
GSM1019232 |
Patient 365, male, squamous |
GSM1019233 |
Patient 367, male, squamous |
GSM1019234 |
Patient 369, female, adeno |
GSM1019235 |
Patient 370, male, squamous |
GSM1019236 |
Patient 373, female, adeno |
GSM1019237 |
Patient 375, female, large |
GSM1019238 |
Patient 5, male, squamous |
GSM1019239 |
Patient 7, male, adeno |
GSM1019240 |
Patient 8, male, squamous |
GSM1019241 |
Patient 10, male, squamous |
GSM1019242 |
Patient 16, female, adeno |
GSM1019243 |
Patient 20, male, adeno |
GSM1019244 |
Patient 28, female, adeno |
GSM1019245 |
Patient 29, male, squamous |
GSM1019246 |
Patient 30, female, squamous |
GSM1019247 |
Patient 36, male, adeno |
GSM1019248 |
Patient 38, male, large |
GSM1019249 |
Patient 41, female, adeno |
GSM1019250 |
Patient 43, male, squamous |
GSM1019251 |
Patient 52, female, squamous |
GSM1019252 |
Patient 55, male, squamous |
GSM1019253 |
Patient 56, male, adeno |
GSM1019254 |
Patient 58, female, adeno |
GSM1019255 |
Patient 59, male, squamous |
GSM1019256 |
Patient 62, female, adeno |
GSM1019257 |
Patient 64, male, adeno |
GSM1019258 |
Patient 66, male, adeno |
GSM1019259 |
Patient 68, female, adeno |
GSM1019260 |
Patient 74, male, adeno |
GSM1019261 |
Patient 75, male, adeno |
GSM1019262 |
Patient 76, male, large |
GSM1019263 |
Patient 78, male, squamous |
GSM1019264 |
Patient 79, female, adeno |
GSM1019265 |
Patient 80, female, adeno |
GSM1019266 |
Patient 84, male, squamous |
GSM1019267 |
Patient 92, female, squamous |
GSM1019268 |
Patient 93, male, adeno |
GSM1019269 |
Patient 96, male, squamous |
GSM1019270 |
Patient 101, male, adeno |
GSM1019271 |
Patient 105, male, squamous |
GSM1019272 |
Patient 107, female, adeno |
GSM1019273 |
Patient 110, female, adeno |
GSM1019274 |
Patient 111, female, adeno |
GSM1019275 |
Patient 114, female, adeno |
GSM1019276 |
Patient 116, female, squamous |
GSM1019277 |
Patient 123, male, squamous |
GSM1019278 |
Patient 128, female, squamous |
GSM1019279 |
Patient 130, male, squamous |
GSM1019280 |
Patient 135, male, squamous |
GSM1019281 |
Patient 138, male, squamous |
GSM1019282 |
Patient 139, male, squamous |
GSM1019283 |
Patient 147, female, adeno |
GSM1019284 |
Patient 149, male, squamous |
GSM1019285 |
Patient 150, female, adeno |
GSM1019286 |
Patient 154, male, adeno |
GSM1019287 |
Patient 156, male, large |
GSM1019288 |
Patient 160, female, adeno |
GSM1019289 |
Patient 163, male, adeno |
GSM1019290 |
Patient 164, female, adeno |
GSM1019291 |
Patient 168, female, squamous |
GSM1019292 |
Patient 173, male, adeno |
GSM1019293 |
Patient 178, female, squamous |
GSM1019294 |
Patient 179, male, squamous |
GSM1019295 |
Patient 180, female, adeno |
GSM1019296 |
Patient 182, male, squamous |
GSM1019297 |
Patient 184, female, squamous |
GSM1019298 |
Patient 186, female, adeno |
GSM1019299 |
Patient 187, male, adeno |
GSM1019300 |
Patient 190, male, adeno |
GSM1019301 |
Patient 204, female, large |
GSM1019302 |
Patient 209, female, adeno |
GSM1019303 |
Patient 218, male, adeno |
GSM1019304 |
Patient 220, female, large |
GSM1019305 |
Patient 226, female, adeno |
GSM1019306 |
Patient 236, female, squamous |
GSM1019307 |
Patient 239, male, squamous |
GSM1019308 |
Patient 241, male, adeno |
GSM1019309 |
Patient 244, female, adeno |
GSM1019310 |
Patient 254, female, adeno |
GSM1019311 |
Patient 257, female, adeno |
GSM1019312 |
Patient 263, male, adeno |
GSM1019313 |
Patient 275, female, adeno |
GSM1019314 |
Patient 276, male, adeno |
GSM1019315 |
Patient 277, female, large |
GSM1019316 |
Patient 285, female, adeno |
GSM1019317 |
Patient 287, female, large |
GSM1019318 |
Patient 290, female, adeno |
GSM1019319 |
Patient 294, male, squamous |
GSM1019320 |
Patient 312, male, adeno |
GSM1019321 |
Patient 318, male, adeno |
GSM1019322 |
Patient 320, male, squamous |
GSM1019323 |
Patient 321, male, squamous |
GSM1019324 |
Patient 327, male, adeno |
GSM1019325 |
Patient 329, male, squamous |
GSM1019326 |
Patient 334, male, squamous |
GSM1019327 |
Patient 336, female, large |
GSM1019328 |
Patient 348, male, adeno |
GSM1019329 |
Patient 350, female, squamous |
GSM1019330 |
Patient 353, male, adeno |
GSM1019331 |
Patient 354, male, squamous |
GSM1019332 |
Patient 360, female, adeno |
GSM1019333 |
Patient 363, female, large |
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Relations |
BioProject |
PRJNA165697 |
Supplementary file |
Size |
Download |
File type/resource |
GSE37745_RAW.tar |
939.2 Mb |
(http)(custom) |
TAR (of CEL) |
Processed data included within Sample table |
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