ABSTRACT
Lung cancer is the leading cause of cancer death, and non-small cell lung cancer (NSCLC) accounts for 85%. Immunotherapy has significantly improved the clinical prognosis of patients with NSCLC. However, because of the complexity and heterogeneousness of the tumor microenvironment, only a subset of individuals can benefit from immunotherapy. Therefore, it is necessary to explore effective predictive biomarkers for immunotherapy of NSCLC. Tertiary lymphoid structure (TLS) is an ectopic lymphoid organ that is highly similar to secondary lymphoid organs (SLO), and the presence of TLS has been found to be closely associated with a good prognosis in immunotherapy for a variety of solid tumors, including NSCLC. This article provides a review of the prognostic role of tertiary lymphoid structures in immunotherapy of NSCLC, in order to offer references for screening suitable candidates for immunotherapy of NSCLC and develop personalized and precise treatment plans. .
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/pathology , Tertiary Lymphoid Structures/pathology , Lung Neoplasms/pathology , Prognosis , Immunotherapy , Tumor MicroenvironmentABSTRACT
The inositol polyphosphate kinase (IPK) family member ITPKA (inositol 1,4,5-trisphosphate 3-kinase) regulates the levels of many inositol polyphosphates which are important in cellular signaling. Several recent studies reported the aberrant expression of ITPKA in malignancy disease and usually made cancer more aggressive. However, the contribution of the inositol polyphosphate kinase ITPKA to lung cancer development remains unclear. Here we report that ITPKA is overexpressed in lung adenocarcinoma (LUAD) and positively correlated with advanced clinical parameters. ITPKA contributes to the malignant phenotypes in-vitro. Mechanistically, ITPKA executed its action through the inducting of epithelial-mesenchymal transition (EMT) and interacting with Drebrin 1 (which is related to cancer metastasis). Moreover, the hyper-expression of ITPKA in LUAD is transcriptionally activated by the transcription factor TFAP2A. In survival analysis by using tissue microarray (TMA), we indicate that ITPKA is hyper-expressed in LUAD tissues compared to adjacent normal tissues, and increased expression of ITPKA is associated with poor prognosis. Collectively, this study indicates that TFAP2A induced ITPKA hyperexpression promotes LUAD via interacting with Drebrin 1 and activating epithelial-mesenchymal transition (EMT). ITPKA might represent a potent candidate for the treatment and prognostic prediction of LUAD.
Subject(s)
Adenocarcinoma of Lung/metabolism , Cell Movement/physiology , Lung Neoplasms/metabolism , Neuropeptides/metabolism , Phosphotransferases (Alcohol Group Acceptor)/metabolism , Transcription Factor AP-2/metabolism , Adenocarcinoma of Lung/genetics , Blotting, Western , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Cell Proliferation/physiology , Epithelial-Mesenchymal Transition , Flow Cytometry , Gene Expression Regulation, Neoplastic/genetics , Gene Expression Regulation, Neoplastic/physiology , Humans , Immunohistochemistry , Immunoprecipitation , Lung Neoplasms/genetics , Neuropeptides/genetics , Phosphotransferases (Alcohol Group Acceptor)/genetics , Protein Binding , Transcription Factor AP-2/genetics , Wound Healing/genetics , Wound Healing/physiologyABSTRACT
Objective To investigate the relationship between genetic polymorphisms of ERCC1 and survival rate in advanced non-small cell lung cancer (NSCLC) patients treated with platinum based chemotherapy.Methods A total of 204 patients with advanced NSCLC were routinely treated by platinbased chemotherapy.The polymorphic genotypes were analyzed by MALDI-TOF-MS nethod using DNA samples isolated from peripheral blood before treatment.Besides,5 ％ samples werc extracted randomly for sequencing to test the accuracy of this method.To explored the association between SNP of ERCC1 (118) and prognosis to platinum-based chemotherapy in advanced NSCLC patients.Results Among 204 patients,61 achieved partial response,116 achieved stable response,and 27 achieved progressive disease.The overall response rate was 29.9 ％ (61/204).The effective rates of patients with the ERCC1 (118) C/C genotype,C/T + T/T genotype were 24.0 ％ (29/121) and 38.6 ％ (32/83),respectively,with significant difference (P ＜ 0.05).The response rate of ERCC1 (118) C/T allele carriers was 1.992-fold than that of C/C allele carriers (95 ％ confidence interval:1.083-3.650,P =0.025).MST,1-year survival and 2-year survival rates of patients with the ERCC1 (118) C/C genotype,C/T + T/T genotype were 9.0 months,34.7 ％ (42/121) and 4.1％ (5/121) vs 12.0 months,60.2 ％ (50/83) and 12.0 ％ (10/83),respectively,with significant difference (P ＜ 0.05).Conclusions Polymorphisms of ERCC1 might be associated with overall survival period in patients with advanced NSCLC after treatment with platin-based chemotherapy,which might be the predictive markers for overall survival.
