PMID- 29184444
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220317
IS  - 1179-1349 (Print)
IS  - 1179-1349 (Electronic)
IS  - 1179-1349 (Linking)
VI  - 9
DP  - 2017
TI  - Development and validation of a panel of five proteins as blood biomarkers for 
      early detection of colorectal cancer.
PG  - 517-526
LID - 10.2147/CLEP.S144171 [doi]
AB  - OBJECTIVE: Reliable noninvasive biomarkers for early detection of colorectal 
      cancer (CRC) are highly desirable for efficient population-based screening with 
      high adherence rates. We aimed to discover and validate blood-based protein 
      markers for the early detection of CRC. PATIENTS AND METHODS: A two-stage design 
      with a discovery and a validation set was used. In the discovery phase, plasma 
      levels of 92 protein markers and serum levels of TP53 autoantibody were measured 
      in 226 clinically recruited CRC patients and 118 controls who were free of 
      colorectal neoplasms at screening colonoscopy. An algorithm predicting the 
      presence of CRC was derived by Lasso regression and validated in a validation set 
      consisting of all available 41 patients with CRC and a representative sample of 
      106 participants with advanced adenomas and 107 controls free of neoplasm from a 
      large screening colonoscopy cohort (N=6018). Receiver operating characteristic 
      (ROC) analyses were conducted to evaluate the diagnostic performance of 
      individual biomarkers and biomarker combinations. RESULTS: An algorithm based on 
      growth differentiation factor 15 (GDF-15), amphiregulin (AREG), Fas antigen 
      ligand (FasL), Fms-related tyrosine kinase 3 ligand (Flt3L) and TP53 autoantibody 
      was constructed. In the validation set, the areas under the curves of this 
      five-marker algorithm were 0.82 (95% CI, 0.74-0.90) for detecting CRC and 0.60 
      (95% CI, 0.52-0.69) for detecting advanced adenomas. At cutoffs yielding 90% 
      specificity, the sensitivities (95% CI) for detecting CRC and advanced adenomas 
      were 56.4% (38.4%-71.8%) and 22.0% (13.4%-35.4%), respectively. The five-marker 
      panel showed similar diagnostic efficacy for the detection of early- and 
      late-stage CRC. CONCLUSION: The identified most promising biomarkers could 
      contribute to the development of powerful blood-based tests for CRC screening in 
      the future.
FAU - Chen, Hongda
AU  - Chen H
AD  - Division of Clinical Epidemiology and Aging Research, German Cancer Research 
      Center (DKFZ), Heidelberg, Germany.
AD  - Program Office for Cancer Screening in Urban China, National Cancer Center/Cancer 
      Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 
      Beijing, People's Republic of China.
FAU - Qian, Jing
AU  - Qian J
AD  - Division of Clinical Epidemiology and Aging Research, German Cancer Research 
      Center (DKFZ), Heidelberg, Germany.
FAU - Werner, Simone
AU  - Werner S
AD  - Division of Clinical Epidemiology and Aging Research, German Cancer Research 
      Center (DKFZ), Heidelberg, Germany.
FAU - Cuk, Katarina
AU  - Cuk K
AD  - Division of Clinical Epidemiology and Aging Research, German Cancer Research 
      Center (DKFZ), Heidelberg, Germany.
FAU - Knebel, Phillip
AU  - Knebel P
AD  - Department of General, Visceral and Transplantation Surgery, University of 
      Heidelberg.
FAU - Brenner, Hermann
AU  - Brenner H
AD  - Division of Clinical Epidemiology and Aging Research, German Cancer Research 
      Center (DKFZ), Heidelberg, Germany.
AD  - Division of Preventive Oncology, German Cancer Research Center (DKFZ) and 
      National Center for Tumor Diseases.
AD  - German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 
      Heidelberg, Germany.
LA  - eng
PT  - Journal Article
DEP - 20171031
PL  - New Zealand
TA  - Clin Epidemiol
JT  - Clinical epidemiology
JID - 101531700
PMC - PMC5672848
OTO - NOTNLM
OT  - adenoma
OT  - amphiregulin
OT  - colorectal cancer
OT  - growth differentiation factor 15
OT  - screening
COIS- Disclosure Hermann Brenner and Hongda Chen have applied for a patent "Biomarker 
      panel for diagnosing cancer." The other authors report no conflicts of interest 
      in this work.
EDAT- 2017/12/01 06:00
MHDA- 2017/12/01 06:01
PMCR- 2017/10/31
CRDT- 2017/11/30 06:00
PHST- 2017/11/30 06:00 [entrez]
PHST- 2017/12/01 06:00 [pubmed]
PHST- 2017/12/01 06:01 [medline]
PHST- 2017/10/31 00:00 [pmc-release]
AID - clep-9-517 [pii]
AID - 10.2147/CLEP.S144171 [doi]
PST - epublish
SO  - Clin Epidemiol. 2017 Oct 31;9:517-526. doi: 10.2147/CLEP.S144171. eCollection 
      2017.