The Expression And Clinical-biological Significance Of HLJ1in Colorectal Carcinoma

Objective: The implication of human liver DnaJ-like protein (HLJ1), amember of the heat shock protein-40chaperone family, in non-small cell lungcancer (NSCLC) and hepatocellular carcinoma (HCC) has been confirmed butin colorectal carcinoma (CRC) remains unclear. The aim of this study was todetermine the expression of HLJ1in CRC cell lines and CRC carcinoma tissues,adjacent normal mucosa tissues and lymph node metastasis tissues of CRCpatients, analyze the relationship between HLJ1level and clinicopathologicalcharacteristics of CRC patients, and compare the survival rate of CRC patientswith different expression of HLJ1level, then investigate the biologicalsignificance of HLJ1in colorectal carcinoma. Methods: Both real-time reversetranscription PCR (RT-PCR) and Western blot were used to detect theexpression of HLJ1in five kinds of lowly metastatic CRC cell lines and twokinds of highly metastatic CRC cell lines, while the distribution of HLJ1in147cases of CRC carcinoma tissues, its adjacent normal mucosa tissues and lymphnode metastasis tissues from CRC patients was determined withimmunohistochemistry (IHC). Then analyze the relationship between HLJ1expression and patients’ clinicopathologic features include age, gender, tumorsize, differentiation, serosal invasion, lymph node metastasis, lymph node metastasis rate (LNR), Dukes’ stage and remote metastasis, and compare thedifference in survival of patients with different expression levels HLJ1usingthe Kaplan-Meier survival analysis method. Results: The results indicated thatin lowly metastatic CRC cells, the HLJ1gene expression was fourfold higherthan that in highly metastatic ones, and Western blot analysis also showed HLJ1protein in lowly metastatic CRC cells was higher than in highly metastatic ones,that the HLJ1expression was significantly down-regulated in CRC orlymphatic metastatic tissues from147cases of CRC patient compared to that inthe normal mucosa tissues (P<0.01), and HLJ1in CRC tissues with lymphaticmetastasis was significantly lower than those without lymphatic metastasis(P<0.01), but without significant difference to lymphatic metastatic tissues(P>0.05). Otherwise, the HLJ1expression was correlated strongly with lymphmetastasis, Dukes’ stage, and remote metastasis (P<0.05), but not with age,gender, tumor size, differentiation, serosal invasion, lymph node metastasis.Interestingly, patients with a higher HLJ1level had a better overall survival ratecompared to that in patients with lower HLJ1level (P<0.05). From univariateanalysis, the significant prognostic factors were HLJ1expression, TumorGrade, lymph metastasis, LNR, Dukes’ stage and remote metastasis (P<0.05),Multivariate analysis results showed that HLJ1expression and lymphaticmetastasis might play a role in predicting the overall survival in CRC patients(P<0.05). Conclusion: HLJ1is a strong tumor suppressor for CRC, and showdynamic changes in CRC both in vitro and in vivo, there exhibit correlation between HLJ1expression and clinicopathologic features, and CRC patientswho with higher HLJ1level have a longer survival. Thus, HLJ1may beinvolved in proliferation, progression, invasion of CRC. A down-regulation ofHLJ1expression may be used as a biomarker to predict clinical outcome ofpatients with CRC.