Analysis Of Prognostic Factors In Small Cell Lung Cancer

Objective:To investigate prognostic factors and biomarkers of the distant-metastasis free survival(DMFS)of limited stage small cell lung cancer(LS-SCLC)patients and radio-sensitivity of the SCLC cell lines.Methods:The clinical data of 104 patients primarily diagnosed as limited stage small cell lung cancer and later confirmed metastasis at Shandong Cancer Hospital affiliated to Shandong University from December 2009 to July 2017 were analyzed retrospectively.Their clinical and first blood test data prior to chemotherapy and radiotherapy including age,gender,BMI,lymphocyte count,platelet count,albumin,prealbumin,LDH and with or without thoracic radiation therapy(TRT)interval were collected and analyzed with SPSS 24.0.SCLC cell lines data of gene expression microarray(GSE55830)was downloaded from GEO database.BRB-ArrayTools was used for analyzing the data.DAVID was used for gene annotation and KEGG pathway determination.NCBI BLAST was used for aligning RNAs of pseudogenes and genes.catRAPID was used for predicting proteins binding with pseudogenes or its RNA transcript.miRDB was used for predicting microRNAs binding with RNAs.Combining online database search about the expression level of PPIAP43 and the true gene PPIA given.out by the previous step was executed.The difference between the expression level of PPIA in normal tissues and tumors was compared,and the relationship between the expression of PPIA and the prognosis of cancer patients was explored.Results:The 0.5-,1-,1.5-,2-year DMFS rates were 68.3%,34.6%,15.5%,2.9%respectively.Univariate analysis revealed that prealbumin(PA)?0.2g/L,platelet count<6 ×109/L,no thoracic RT interval(NTRT)were risk factors of DMFS.Multivariate analysis demonstrated that prealbumin<0.2g/L and NTRT were independent factors of DMFS.PA?0.2g/L occurred in 22.7%of the patients.The median DMFS of patients with PA?0.2g/L was 199.5 days,and the 0.5-,1-,1.5-,2-year DMFS rates of these patients were 50.0%4.5%,0 and 0,respectively;The median DMFS of patients without PA?0.2g/L was 304 days,and the 0.5-,1-,1.5-,2-year DMFS rates of these patients were 73.3%,40.0%,13.3%and 4.0%,respectively.Univariate and multivariate analysis showed that albumin?45g/L was significantly and independently associated with PA?0.2g/L.NTRT occurred in 22.7%of the patients.The median DMFS of patients with NTRT was 103 days,and the 0.5-,1-,1.5-,2-year DMFS rates of these patients were 31.0%?17.2%?3.4%?0,respectively;The median DMFS of patients with TRT was 302 days,and the 0.5-,1-,1.5-,2-year DMFS rates of these patients were85.3%?41.3%?16.0%?4.0%,respectively.RNA transcript of PPIAP43 was 2-fold up-regulated by 2 Gy gamma radiation in cell line H69,H128,H146,H209 and H187.These cells shared 355 co-regulated RNAs after radiation.H526,D53,D114,D153 without PPIAP43 over-transcribed by 2-fold shared 12 co-regulated RNAs.RNA transcript of PPIAP43 was aligned with 3'UTR of mRNAs of PPIA;miRNA hsa-miR-876-3p was predicted to bind with this aligned section.High expression level of PPIA was found in 17 out of 17 cancer types compared with normal adjacent tissues.High expression of PPIA was of inferior overall survival in low grade glioma(LGG),acute myeloid leukemia(LMAL),lung adenocarcinoma(LUAD),skin cutaneous melanoma(SKCM)and liver hepatocellular cancer.The prognostic effect of PPIA expression level in LIHC was independent of tumor grade.High expression level of PPIA was of special prognostic value in stage 3,AJCC T3,HBV negative and sorafenib taken subgroups in LIHC.Conclusion:Prealbumin?0.2g/L in first blood test prior to chemo and no thoracic RT interval were important factors affecting DMFS in patients with LS-SCLC.Serum albumin?45g/L was only risk factor of prealbumin?0.2g/L.the change pattern of transcription level of PPIAP43 before and after radiation linked with the radio-sensitivity of SCLC.Over 2-fold up-transcription of PPIAP43 may indicate higher sensitivity such as cell line H146,H69,H187 and H209;lower transcription was of lower sensitivity such as D153 and H526.In conclusion,we found a biomarker candidate PPIAP43 for predicting radio-sensitivity of SCLC cells in vitro.High expression level of PPIA is related with prognoses of multiple cancer types.Especially,high expression level of PPIA is of special prognostic value in stage 3,AJCC T3,HBV negative and sorafenib taken subgroups in LIHC.The expression level of PPIA is significantly associated with expression levels of BSG and STAT3,which may be major effectors of PPIA in cancerous progression.