Diagnosis And Prognosis Value Of INSM1 In Neuroendocrine Tumors Of The Prostate

Background and Objectives Neuroendocrine Tumor of the Prostate(NEPC)is a special pathological type in prostate cancer with a low incidence rate.NEPC has a varitery of subtypes,and the clinical manifestations and prognosis of different subtypes are quite different.Therefore,the diagnosis of NEPC and the differential diagnosis between various subtypes have important clinical significance.Insulinoma-associated protein 1(INSM1)is a transcription factor containing a zinc finger domain and is widely involved in the development of the neuroendocrine system.However,its role in the diagnosis of NEPC is unclear.In addition,prostate cancer with neuroendocrine differentiation is easily confused with Paneth cell-like changes,and the prognosis of patients is still controversial.To this end,this study will analyze the NEPC patient cohort admitted to our hospital,to determine the role of INSM1 in the diagnosis of NEPC,and to explore the relationship between neuroendocrine differentiation and prognosis in patients with prostate cancer.Materials and Methods 1.Retrospective analysis of clinical and pathological data of patients with NEPC admitted from 2010 to 2017;2.Compare the difference of INSM1 m RNA expression levels between NEPC and prostate adenocarcinoma through clinical public database;3.Collect paraffin sections of NEPC patients and construct pathological tissue microarrays of prostate adenocarcinoma and benign prostatic hyperplasia.Immunohistochemical staining was used to detect the expression and distribution of INSM1.Comparison of the specificity and sensitivity of INSM1 with first-line neuroendocrine markers CHGA and SYP in the diagnosis of NEPC;4.Extract RNA and protein from different prostate cancer cell lines,and detect the expression level of INSM1 by q RT-PCR and Western blotting,respectively;5.Immunohistochemical staining was used to detect the expression and distribution of INSM1,CHGA and SYP in prostate adenocarcinoma with neuroendocrine differentiation and Paneth cell-like changes.The relationship between neuroendocrine differentiation and clinicopathological factors and prognosis in patients with prostate adenocarcinoma was investigated through positive expression of INSM1.Results 1.A total of 20 patients with NEPC were enrolled in the study,including 13 of small cell carcinoma.Although platinum-based chemotherapy is effective at early stage,the prognosis is generally poor.The first-line neuroendocrine markers CHGA and SYP lack sufficient sensitivity and are often need to used in combination in clinical practice;2.Results from clinical public database and immunohistochemical staining suggest that INSM1 is highly expressed in tumor tissues of NEPC patients,and its sensitivity in diagnosis of small cell carcinoma is higher than that of CHGA and SYP.Cell line experiment also indicated that the NEPC cell line specifically expressed INSM1;3.INSM1 is specifically expressed in prostate neuroendocrine differentiated tissues and is not expressed in Paneth cell-like changes.Neuroendocrine differentiation is closely associated with local lymph node metastasis.The incidence of clinical progression in patients with neuroendocrine differentiation was significantly higher than that in patients without neuroendocrine differentiation.Multivariate regression analysis confirmed that neuroendocrine differentiation is an independent risk factor for clinical progression after the surgery.Conclusions 1.INSM1 is highly expressed in NEPC tumor tissues and cell lines,and can be used as a first line diagnostic marker for prostate small cell carcinoma;2.INSM1 is specifically expressed in neuroendocrine differentiated tissues of prostate cancer;prostate adenocarcinoma with neuroendocrine differentiation is closely related to local tumor progression,and is an independent risk factor for postoperative clinical progression in patients with prostate carcinoma.