title: Loss of p16INK4, alone and with overexpression of osteopontin, correlates with survival of patients with spinal metastasis from hepatocellular carcinoma.
abstract: The survival of patients with hepatocellular carcinoma (HCC) has been improved with various diagnostic tools and treatment modalities. Consequently, spinal metastases from HCC are diagnosed more frequently. We investigated the clinical biomarkers of HCC patients presenting with spinal metastasis. Between January 2001 and December 2007, we recruited 30 consecutive HCC patients presenting with spinal metastasis. Their tissue samples were collected and analyzed by immunohistochemistry in a tissue microarray. A total of 16 proteins were assessed in the tissue microarray; we found that expression of p16(INK4) correlated with the survival time (log-rank test, P = 0.05), and loss of p16(INK4) was significantly associated with osteopontin overexpression (Fisher exact test: P = 0.045, logistic regression: P = 0.024, OR = 0.184, 95% CI 0.035-0.963). Patients with osteopontin (-) and with p16(INK4) (+) lived longer than patients with osteopontin (+) and with p16(INK4) (-). We found that p16(INK4) and osteopontin might be the biomarkers of patients with spinal metastasis from HCC, a more large-scaled randomized study might be required to confirm the result and study the mechanism.
authors.affiliation: Department of Orthopedic Surgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, 200003, Shanghai, China. dr.huajiang@gmail.com
authors.forename: Hua-jiang
authors.initials: HJ
authors.lastname: Chen
authors.forename: Jian-ru
authors.initials: JR
authors.lastname: Xiao
authors.forename: Wen
authors.initials: W
authors.lastname: Yuan
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis* / Q000172:deficiency; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D019942:Genes, p16; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D053495:Osteopontin / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D010243:Paralysis / Q000209:etiology; D013117:Spinal Cord Compression / Q000209:etiology; D013125:Spinal Neoplasms / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D013997:Time Factors
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D053495:Osteopontin