Correlation Of PC4 Overexpression With Lymphatic Metastasis And Prognosis In Lung Adenocarcinoma

Background and objectiveMetastasis, including lymphatic metastasis, remains a main cause for poor prognosis of cancer patients. The human transcriptional positive cofactor 4(PC4) is identified as a key factor in physiological genetic process such as transcription, replication and cell cycle progression and is suggested to be a novel marker for the diagnosis and treatment of advanced human cancers with metastasis. The aim of our study was to evaluate the clinical significance of PC4 in lymphatic metastasis and prognosis of lung adenocarcinoma.MethodsSamples from 5 different sites of 96 patients with lung adenocarcinoma were collected, including adenocarcinoma tissues(n=96), para-tumor lung tissues(n=30), distant nontumorous lung tissues(n=30), positive lymph nodes(n=45) and negative lymph nodes(n=54). PC4 protein expression levels of the 5 groups were measured by immunohistochemistry(IHC). PC4 protein and mRNA expressions in adenocarcinoma of the 96 cases were respectively obtained by immunohistochemistry and q RT-PCR assay and were evaluated for their clinical significance. Furthermore, survival analysis was adopted to investigate the correlation of PC4 protein expression of another 83 lung adenocarcinoma patients.ResultsPC4 was expressed at the highest level in positive lymph nodes, followed by adenocarcinoma and para-tumor lung tissue groups, and the lowest in distant nontumorous lung tissues and negative lymph nodes(p<0.05). PC4 protein expression was positively correlated with m RNA(r=0.626, p<0.01). Both protein and mRNA expressions of PC4 were significantly associated with lymph node metastasis and TNM stage(PC4 protein: χ2=8.400, p=0.004 for lymph node metastasis, χ2=5.097, p=0.030 for TNM stage; PC4 mRNA: χ2=8.291, p=0.004 for lymph node metastasis, χ2=4.714, p=0.024 for TNM stage). Higher level of PC4 indicated a poorer prognosis(p=0.002 for overall survival(OS); p=0.010 for progression-free survival(PFS)). Shorter median OS and PFS were found in patients with higher expression of PC4 protein(21 vs. 39 months for OS, 21 vs. 33 months for PFS). Additionally, the expression level of PC4 protein was an important risk factor for survival in our univariate analyses(OS: HR=2.135, p=0.004; PFS: HR=1.848, p=0.013).Conclusions1. Different PC4 protein expressions were observed in respective tissues from lung adenocarcinoma cases, the highest in positive lymph nodes, followed by adenocarcinoma and para-tumor lung tissues, and lowest in distant nontumorous lung tissues and negative lymph nodes.2. PC4 expression was significantly associated with lymph node metastasis and TNM stage. Patients with PC4 overexpression were more likely to be accompanied with lymph node metastasis and higher TNM stage.3. PC4 was negatively correlated with prognosis. Both OS and PFS were significantly shorter in patients with higher PC4 level.