title: Serum haptoglobin as a novel molecular biomarker predicting colorectal cancer hepatic metastasis.
abstract: Early detection of liver metastasis is important for improving colorectal cancer (CRC) patient survival. Our previous studies showed haptoglobin was highly expressed in primary CRC tissues, especially in heterochronous metastatic cases. Here, we assessed the potential of serum haptoglobin (sHP) as a biomarker for early detection of CRC liver metastasis by evaluating the sHP in 475 CRC patients and 152 healthy volunteers. In the training set (250 cases), sHP level in CRC-M1 (1773.18 ± 690.25 ng/mL) were significantly increased as compared to in CRC-M0 (1544.37 ± 1497.65 ng/mL) or healthy (917.76 ± 571.59 ng/mL). And the high sHP level was correlated with poor survival. Logistic regression analysis revealed that sHP, serum carcinoembryonic antigen (sCEA) and serum carbohydrate antigen 19.9 (sCA19.9) level were the significant parameters for detecting liver metastasis. In leave-one-out-cross-validation, these three markers resulted in 89.1% sensitivity and 85.8% specificity for hepatic metastasis detection. In an independent test set (225 cases), receiver operating characteristic curve analysis of sHP in CRC liver metastasis showed an area under the curve of 0.735, with a sensitivity of 87.2% and a specificity of 59.9%. Combination of sHP, sCEA and sCA19.9 improved diagnostic accuracy to 0.880, with a sensitivity of 88.5% and a specificity of 87.8%. Silencing of HP by specific shRNA significantly inhibited the LOVO and SW620 cell invasion, and suppressed xenograft tumor invasive growth. In summary, these results demonstrate that sHP is associated with poor prognosis of CRC patients and that HP promotes colorectal cancer cell invasion. sHP combining with sCA19.9 and sCEA may be used as accurate predictors of CRC liver metastasis.
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Hospital, Beijing, People's Republic of China.
authors.forename: Lichao
authors.initials: L
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Hospital, Beijing, People's Republic of China.
authors.forename: Shusheng
authors.initials: S
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Hospital, Beijing, People's Republic of China.
authors.forename: Long
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Abdominal Surgical Oncology, Cancer Hospital, Beijing, People's Republic of China.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Hospital, Beijing, People's Republic of China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Hospital, Beijing, People's Republic of China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Clinical Laboratory, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Hospital, Beijing, People's Republic of China.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Ran
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D018395:CA-19-9 Antigen / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood; D015179:Colorectal Neoplasms / Q000097:blood* / Q000473:pathology; D005260:Female; D006242:Haptoglobins / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood* / Q000473:pathology / Q000556:secondary; D008297:Male; D051379:Mice; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D011379:Prognosis; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D002272:Carcinoembryonic Antigen; D006242:Haptoglobins
keywords: biomarker; colorectal cancer; haptoglobin; liver metastasis; prognosis