title: A system for tumor heterogeneity evaluation and diagnosis based on tumor markers measured routinely in the laboratory.
abstract: OBJECTIVE
  To develop an efficient and reliable approach to estimate tumor heterogeneity and improve tumor diagnosis using multiple tumor markers measured routinely in the clinical laboratory.
  
  
  METHODS
  A total of 161 patients with different cancers were recruited as the cancer group, and 91 patients with non-oncological conditions were required as the non-oncological disease group. The control group comprised 90 randomly selected healthy subjects. AFP, CEA, CYFRA, CA125, CA153, CA199, CA724, and NSE levels were measured in all these subjects with a chemiluminescent microparticle immunoassay. The tumor marker with the maximum S/CO value (sample test value:cutoff value for discriminating individuals with and without tumors) was considered as a specific tumor marker (STM) for an individual. Tumor heterogeneity index (THI)=N/P (N: number of STMs; P: percentage of individuals with STMs in a certain tumor population) was used to quantify tumor heterogeneity: high THI indicated high tumor heterogeneity. The tumor marker index (TMI), TMI = STM×(number of positive tumor markers+1), was used for diagnosis.
  
  
  RESULTS
  The THIs of lung, gastric, and liver cancers were 8.33, 9.63, and 5.2, respectively, while the ROC-areas under the curve for TMI were 0.862, 0.809, and 0.966.
  
  
  CONCLUSIONS
  In this study, we developed a novel index for tumor heterogeneity based on the expression of various routinely evaluated serum tumor markers. Development of an evaluation system for tumor heterogeneity on the basis of this index could provide an effective diagnostic tool for some cancers.
authors.affiliation: Department of Clinical Immunology, Dalian Medical University, Dalian 116044, China. Electronic address: liuhui60@sina.com.
authors.forename: Liu
authors.initials: L
authors.lastname: Hui
authors.affiliation: Department of Clinical Immunology, Dalian Medical University, Dalian 116044, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Rixv
authors.affiliation: Department of Clinical Immunology, Dalian Medical University, Dalian 116044, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Xiuying
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000097:blood / Q000235:genetics; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000097:blood / Q000235:genetics; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D018394:CA-125 Antigen / Q000097:blood / Q000235:genetics; D018395:CA-19-9 Antigen / Q000097:blood / Q000235:genetics; D002272:Carcinoembryonic Antigen / Q000097:blood / Q000235:genetics; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D053539:Keratin-19 / Q000097:blood / Q000235:genetics; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood / Q000235:genetics; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010751:Phosphopyruvate Hydratase / Q000097:blood / Q000235:genetics; D011379:Prognosis; D012372:ROC Curve; D013274:Stomach Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000509:alpha-Fetoproteins / Q000235:genetics / Q000378:metabolism
chemical_list: C097353:AFP protein, human; D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D018395:CA-19-9 Antigen; C083825:CA-72-4 antigen; D002272:Carcinoembryonic Antigen; D053539:Keratin-19; D018396:Mucin-1; D000509:alpha-Fetoproteins; C102012:antigen CYFRA21.1; D010751:Phosphopyruvate Hydratase
keywords: Evaluation system; Serum tumor markers; Tumor heterogeneity; Tumor heterogeneity index; Tumor marker index