Systematic Reviews
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World J Gastroenterol. Oct 28, 2014; 20(40): 14958-14964
Published online Oct 28, 2014. doi: 10.3748/wjg.v20.i40.14958
Detection of pancreatic cancer with normal carbohydrate antigen 19-9 using protein chip technology
Xiao-Li Jin, Bin Xu, Yu-Lian Wu
Xiao-Li Jin, Bin Xu, Department of Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, Zhejiang Province, China
Yu-Lian Wu, Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
Author contributions: Jin XL, Xu B and Wu YL performed this research; Wu YL designed the research.
Correspondence to: Yu-Lian Wu, MD, PhD, Professor, Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310009, Zhejiang Province, China. wuyulian@medmail.com.cn
Telephone: +86-571-87784604 Fax: +86-571-87784604
Received: January 4, 2014
Revised: April 14, 2014
Accepted: June 13, 2014
Published online: October 28, 2014
Processing time: 298 Days and 7.3 Hours
Abstract

AIM: To develop a method to differentiate pancreatic cancer patients from healthy or benign individuals when carbohydrate antigen (CA) 19-9 is normal.

METHODS: Forty-one serum samples from patients with pancreatic lesions and blood samples from 20 healthy individuals were collected at the first stage of the experiment according to the enrolment criteria. General characteristics and some clinical features were carefully compared to ensure that the results were reasonable. All the blood samples were analyzed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) combined with CM10 chips and a related bioinformatics analysis program to generate diagnostic models with different proteins. Forty-seven consecutive samples were tested at the next stage to verify the veracity and efficiency of the models.

RESULTS: The sex, age, and serum CA19-9 levels among the three groups (malignant, benign, and healthy) were statistically matched (P values were 0.957, 0.145, and 0.382, respectively). Two patterns were generated. Pattern 1 with four proteins theoretically had a specificity and sensitivity of 100% in distinguishing pancreatic cancer from healthy individuals, while it was 86.7% and 86.4%, respectively, in the subsequent practical verification. The positive predictive value (PPV) of the model was 86.4%. One of the four proteins was expressed highly in pancreatic cancer while the other three were expressed weakly. Pattern 2 consisted of six proteins that showed a specificity of 70.0% and sensitivity of 77.3% for differentiating malignancy from benign tumors. Its PPV reached 85.0%. Only one of these six proteins showed high expression in the malignant group.

CONCLUSION: SELDI-TOF-MS may facilitate diagnosis or differential diagnosis of pancreatic cancer when CA19-9 is normal. Pattern 1 may serve as a useful screening tool.

Keywords: Carbohydrate antigen 19-9; Diagnosis; Pancreatic cancer; Screening; Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry

Core tip: Our study focused on patients with malignant disease and normal carbohydrate antigen 19-9 levels who could be easily misdiagnosed clinically. With careful design, our results could provide early diagnostic models to discriminate cancer patients from healthy volunteers or people with benign disease, as well as some potentially important proteins that could serve as tumor/cancer-specific or -associated antigens in future clinical studies.