The Correlation And Clinical Significance Of TPX2 And ASPM Expression In Prostate Cancer

Background and Objective: Prostate cancer is one of the most common malignancies in the world.It ranks second among common malignancies in Europe and the United States.In the United States,the incidence of prostate cancer ranks first in all malignancies,and the mortality rate ranks second only to lung cancer.Although the incidence of male prostate cancer in China is lower than that in Europe and the United States,it has shown a clear upward trend in recent years.PSA is the most commonly used prostate cancer screening indicator currently.PSA is tissue-specific,and its elevation is closely related to prostate cancer,benign prostatic hyperplasia,and prostatitis,but it is not tumor specific.Prostate biopsy is the most reliable basis for diagnosing prostate cancer.There is still a certain degree of biochemical recurrence after radical prostatectomy,and the prognosis of prostate cancer is closely related to the Gleason score.Therefore,it is necessary to research more sensitive,specific and accurate tumor markers that can accurately reflect the risk of postoperative biochemical recurrence of prostate cancer.Cells are controlled by a series of elaborate events called cell cycles,in which chromosomes and other components are replicated and then distributed into two daughter cells.In the evolution of tumors,mutation is a key driving force.Most cancer cells show varying degrees of genetic instability caused by mutations in genes which control DNA replication,DNA damage response,and regulate chromosomal behavior in mitosis.TPX2(targeting protein for Xklp2)was first discovered in Xenopus in 1998,named for the target protein of Xklp2,which is an important factor involved in cell mitosis and spindle assembly.Its expression is strictly regulated by the cell cycle.Its overexpression is related to chromosomal instability(CIN).In recent years,there have been reports that the gene has been overexpressed in various malignant tumors and positively correlated with the pathological grading and poor prognosis.The full name of ASPM(abnormal spindle-like microcephaly-associated protein)is the human abnormal spindle-like microcephaly-associated protein.The ASPM gene is a human ortholog of the abnormal spindle(asp)of Drosophila and is the most common mutant gene of primary autosomal recessive microcephaly.Studies have found its role in cell cycle progression.At present,there are some reports in the literature that ASPM has overexpression in malignant tumors.We used literary search,database analysis,immunohistochemical analysis,and survival analysis to identify TPX2 and ASPM as the subject of this study,and research the correlation and clinical significance of TPX2 and ASPM expression in prostate cancer.Material and Methods: 1.The proteins of TPX2 and ASPM were detected by immunohistochemical staining on tissue microarrays(TMAs purchased from Xi’an Elina Biotech Co.,Ltd.);the TCGA database which contained the m RNA expression levels of TPX2 and ASPM was downloaded from the Internet.2.By analyzing the immunohistochemistry results of TPX2 and ASPM in tissue microarrays and their m RNA expression in TCGA database,we studied the correlation of TPX2 and ASPM expression,and the relationship between their expression and clinicopathological parameters.3.Through survival curve analysis,the effects of TPX2,ASPM expression and co-expression of TPX2 and ASPM on the overall survival rate and biochemical recurrence survival rate of prostate cancer patients were studied.4.Statistical Processing: Statistical analysis of data was processed using SPSS 17.0 statistical software.The tissue chip staining results were graded data using rank sum test analysis.Statistical analysis of TCGA data was performed using two independent samples t-tests,and continuous variables were shown as mean±SD.The Kolmogorov-Smirnov(K-S)test was used to evaluate whether the TPX2 and ASPM chip value distributions in the TCGA database were normally distributed.Spearman correlation analysis was used to analyze the correlation between TPX2 and ASPM protein levels in the woven microarray.Pearson correlation analysis was used to analyze the correlation between TPX2 and ASPM m RNA levels in the TCGA database.Kaplan-Meier method and log-rank test were used for survival analysis.P<0.05 was considered statistically significant.Results: 1.Expression of TPX2 and ASPM in human prostate cancer tissues and benign tissues The results of tissue microarray analysis showed that the immunohistochemical scores of TPX2 and ASPM in PCa tissues were higher than those in benign tissues(P=0.002,0.003).2.The relationship between the expression of TPX2 and ASPM in human prostate cancer and the clinical pathological parameters.The expression of TPX2 and ASPM proteins in tissue microarrays was assessed using immunohistochemical scoring.The statistical results showed that the protein levels of the two genes were statistically significant between the low Gleason score(<7)group and the high Gleason score(≧7)group(P = 0.029,0.036,).In the TCGA database,the m RNA levels of TPX2 and ASPM in patients older than 66 years were higher than those in patients aged <66 years(P= 0.032,0.034).the m RNA levels of TPX2 and ASPM of the patients with high Gleason score(≧7),middle-late stage(III~IV),metastasis,biochemical recurrence of prostate cancer were higher than those of patients with low Gleason score(<7),early stage(I~II)and without metastasis or biochemical recurrence(P < 0.001,all of them).3.The correlation between TPX2 and ASPM and its relationship with clinical prognosis The two-variable Spearman and Pearson correlation analysis of TPX2 and ASPM tissue chip immunohistochemistry scores and TPX2 and ASPM m RNA expressions in the TCGA database were found to be significantly correlated at the 0.1 level(bilateral)(the correlation coefficients were 0.652 and 0.900,respectively),P<0.001.This indicates that TPX2 is positively correlated with ASPM in prostate cancer.Survival analysis using the TCGA database found that patients with high expression of TPX2 and ASPM had higher biochemical recurrence rates than patients with low expression(P = 0.001,P<0.001),and those with high expression and low expression of TPX2 and ASPM.There was no difference in overall survival among patients with prostate cancer(P=0.217,P=0.475).Comparing the patients of low expression of TPX2 with ASPM and the high expression of both,the biochemical recurrence rate of the high expression group was still higher than that of the low expression group.The above data can be seen that with the increase in the degree of malignancy and clinical pathological stage of prostate tumor tissue,the expression of these two genes is also correspondingly increased.The high expression of TPX2 and ASPM may be a risk factor for biochemical recurrence and poor prognosis.Conclusions: 1.The expression of TPX2 and ASPM in prostate cancer tissues is higher than that in normal tissues,and these two proteins are expected to become new prostate cancer molecular markers.2.The expression intensity of TPX2,ASPM genes was positively correlated with the degree of malignancy of prostate cancer,and the expression of TPX2 and ASPM in prostate cancer had a strong correlation,and the clinical pathological features were similar.It is speculated that there may be a molecular biological link between TPX2 and ASPM in the regulation of the prostate cancer cell cycle.3.The expression of TPX2 and ASPM is positively correlated with the risk of biochemical recurrence of prostate cancer.By detecting the expression of these two genes,the risk of biochemical recurrence in prostate cancer patients can be predicted.