ABSTRACT
BACKGROUND: Small cell lung cancer (SCLC) is an aggressive and invasive malignancy that presents at advanced clinical stage with no more effective treatments. Development of a method for its early detection would be useful, also new therapeutic target need to be discovered; however, there is a lack of information about its oncogenic driver gene mutations. OBJECTIVES: We aim to identify the SCLC-related genomic variants that associate with clinical staging and serum protein biomarkers observed in other types of lung cancer. METHODS: We screened formalin-fixed paraffin-embedded (FFPE) biopsy tissues of 32 Chinese SCLC patients using the 303 oncogenic driver gene panel generated by Tiling PCR amplification sequencing (tPAS) and analyzed the patients' corresponding serum protein levels of CYFRA21-1 CEA, NSE, and SCCA. RESULTS: In total, we found 147 SCLC-related mutant genes, among these, three important genes (TP53, RB1, KMT2D) as well as five novel genes LRRK2, BRCA1, PTCH1, ARID2, and APC that altogether occurred in 90% of patients. Furthermore, increased mutations to 6 genes (WT1, NOTCH1, EPHA3, KDM6A, SETD2, ACVR1B) significantly associated with higher serum NSE levels (P = 0.0016) and higher clinical stages II + III compared to stage I (P = 0.06). CONCLUSIONS: Our panel is relatively reliable in detecting the oncogenic mutations of Chinese SCLC patients. Based on our findings, it may be possible to combine SCLC-related mutations and serum NSE for a simple detection of clinical staging.
Subject(s)
Genes, Neoplasm , High-Throughput Nucleotide Sequencing , Lung Neoplasms/genetics , Mutation/genetics , Small Cell Lung Carcinoma/genetics , Aged , Aged, 80 and over , Biomarkers, Tumor/blood , DNA Mutational Analysis , Female , Humans , INDEL Mutation/genetics , Lung Neoplasms/blood , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Oncogenes , Phosphopyruvate Hydratase/blood , Polymorphism, Single Nucleotide/genetics , Small Cell Lung Carcinoma/blood , Small Cell Lung Carcinoma/pathologyABSTRACT
Background and purpose:Exploration of the effective early diagnostic and prognostic markers of non-small cell lung cancer (NSCLC) has important scientiifc signiifcance and clinical value. Recently, the role of long chain non-coding RNA (lncRNA) in the tumor attracts widespread attention. This study intended to investigate the level of lncRNA HOTTIP in NSCLC, the effect of HOTTIP on cell proliferation and its mechanisms.Methods:Expression of lncRNA HOTTIP in tumor and their matched non-tumor tissues were determined by quantitative real-time PCR (qRT-PCR) in NSCLC patients. Then, we analyzed the potential correlation of lncRNA HOTTIP expression levels in tumor tissues with clinicopathological features of NSCLC and clinical outcome. The effects of HOTTIP on NSCLC cell proliferation and apoptosis were tested usingin vitro MTT and lfow cytometric assays. Western blot method was uesd to detect the expressions of proteins.Results:LncRNA HOTTIP expression level was signiifcantly decreased in NSCLC tissues in comparison to adjacent non-tumor tissues (P<0.05). It was also proved that HOTTIP expression was associat-ed with NSCLC histological grade and lymph node metastasis. Moreover, knockdown of HOTTIP expression in A549 cell line decreased proliferation and enhanced apoptosis compared with transfected negative control. Western blot assay showed that the level of Bax protein was signiifcantly increased, whereas Bcl-2 was signiifcantly decreased in HOT-TIP-silencing A549 cell.Conclusion:HOTTIP is a novel prognostic biomarker and a potential therapeutic candidate forNSCLC.
