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The newly released eighth edition of the American Joint Committee on Cancer TNM staging system for lung cancer seeks to improve prognostic accuracy but lacks external validation for small cell lung cancer (SCLC). Moreover, previous studies posed a few questions concerning survival differences for patients with specific site N3 node involvement or single-site metastasis (SSM) in different distant organs. The aim of this study was to validate the eighth edition of the TNM classification for SCLC in an independent multi-institutional cohort from China and answer the questions raised by the previous research.Patients with SCLC from four Chinese cancer centers between 2009 and 2019 were reclassified according to the seventh and eighth edition of the TNM classification. Survival was estimated using the Kaplan-Meier method. Comparisons between adjacent categories and stage groups were performed using Cox proportional hazard regression. R2 statistics were calculated to evaluate the discriminating performance of editions.Of 3384 enrolled cases, 3358 had clinical stage, 537 had pathological stage, and 511 had both. Progressive deterioration of survival was observed with advancing of TNM categories and stages both in the seventh and the eighth edition. The eighth edition stages had a higher R2 statistic than the seventh edition (0.207 versus 0.197). Newly defined categories M1b and M1c and stages IIIC, IVA and IVB in the eighth edition discriminated groups with significantly different prognosis. Patients with N3 contralateral supraclavicular nodes had a significantly worse prognosis than those without (p = 0.032). For patients with single-site metastasis, liver involvement showed a worse prognosis compared to brain involvement (p = 0.030).Our study provided an external validation of the eighth edition of the TNM classification for lung cancer in Chinese patients with SCLC, and confirmed its improved prognostic accuracy compared with the seventh edition. Patients with N3 and M1b might represent heterogeneous populations that warrant further research.

Objective: Lung adenocarcinoma (LUAD) is the most common type of lung cancer. However, predictive biomarkers for early efficacy and prognosis evaluation in patients with surgically resected LUAD are not completely explained. Methods: Differentially expressed genes (DEGs), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were identified between thirteen LUAD tissues and five normal lung tissues were analyzed by RNA sequencing (RNA-Seq). The expression of DEGs was confirmed by qRT-PCR and a validated cohort from GEPIA. Protein-protein interaction (PPI) network of the top 5% DEGs was constructed by STRING and visualized in Cytoscape. Immunofluorescence results were acquired from clinical specimens from LUAD patients. The expression of FHL1 was analyzed by ImageJ. Survival analysis was performed using the GEPIA dataset. Results: Consistent with the RNA-Seq data, validation of DEGs expression by qRT-PCR and GEPIA cohort showed that FHL1 and SLIT3 were down-regulated in LUAD patient tissues compared with non-tumor tissues. Moreover, FHL1 was significantly reduced in LUAD cell lines compared to the bronchial epithelium cell line (P Conclusion: Our findings provide two novel candidates, FHL1 and SLIT3, for prognostic evaluation and treatments after surgery.

Lung cancer (the 5-year survival rate is only about 16%) has a low survival rate, and more-effective drugs are urgently needed. Our team discovered that cortex Periplocae Radicis has obvious toxic effects on various cancer cells, including lung cancer cells. However, the mechanism is not clear. Therefore, we used the PubChem database to obtain periplogenin as the target of therapeutic drugs and the TCGA database to obtain differential genes of lung cancer. The results showed that MMP9, PPARG, BMP2, and TGFB2 were the core proteins of periplogenin acting on lung adenocarcinoma (LUAD), and MMP9, angiotensin-converting enzyme (ACE), BMP2, PPARG, MMP13, MMP3, and TGFB2 were the core proteins of periplogenin acting on lung squamous cell carcinoma (LUCS). Through gene ontology (GO) enrichment analysis, it was found that periplogenin mainly acted on LUAD via fatty acid binding, metallopeptidase activity, and monocarboxylic acid binding, and mainly acted on lung squamous carcinoma (LUSC) via endopeptidase activity, metallopeptidase activity, and serine-type peptidase activity. Kyoto Encyclopedia of Genes, and Genomes (KEGG) analysis revealed that the IL-17 signaling pathway, fluid shear stress, atherosclerosis, hepatocellular carcinoma, and so on, were the main signaling pathways of periplogenin acting on LUSC, whereas glycolysis/gluconeogenesis, and the peroxisome proliferator-activated receptor (PPAR) signaling pathway were major signaling pathways of periplogenin acting on LUAD. This shows that treatment of lung cancer can be achieved through multi-targeted, and multi-channel periplogenin activity.

Lung adenocarcinoma (LUAD) accounts for approximately half of patients in lung cancer. Cancer-associated fibroblasts (CAFs) are the major component in the tumor microenvironment (TME). Targeting CAFs is a promising therapeutic strategy for cancer treatment. However, therapeutic targets of CAFs in LUAD remains largely unclear. Seven CAFs and nine normal fibroblasts (NFs) were isolated from tumor and paratumor tissues of LUAD patients undergoing surgery, respectively. RNA-seq and bioinformatics analysis were performed to identify the differentially expressed genes (DEGs) and their functions in CAFs compared with NFs. DEGs of ten overlaying were obtained from RNA-seq, our previously reported lncRNA microarray and public datasets (E-MTAB-6149, E-MTAB-6653) and validated by RT-qPCR. Nik-related kinase (NRK) was further validated by RT-qPCR, immunofluorescence (IF), Western Blot (WB) in vitro, and in Cancer Cell Line Encyclopedia (CCLE) database. Survival analysis was performed on Kaplan–Meier plotter. A total of 1799 DEGs were identified, including 650 upregulated DEGs and 1149 downregulated DEGs. The upregulated and downregulated DEGs were mostly enriched in extracellular matrix (ECM) functions and in glycolysis/gluconeogenesis pathways. Interestingly, NRK was the most significantly upregulated overlaying DEGs which was rarely associated with CAFs before. NRK was predominantly expressed in CAFs, but weakly expressed in NFs, normal lung bronchial epithelial cell line BEAS-2B, LUAD cell lines A549 and H1299, as well as in the majority of 191 lung cancer cell lines including LUAD. Moreover, elevated NRK predicted poor survival in LUAD patients. Here, we first report that NRK is significantly elevated in LUAD-associated CAFs and may function as a promising therapeutic target for cancer combination treatment. Besides, modulation of ECM and glycolysis/gluconeogenesis pathways may be an efficient approach to alter CAFs functionality in LUAD.

Metastasis is an unavoidable event happened among almost all small cell lung cancer (SCLC) patients. However, the molecular driven factors have not been elucidated. Recently, a novel hydrolase called cell migration inducing hyaluronidase (CEMIP) triggered both migration and invasion in many tumors but not SCLC. Therefore, in this study, we verified that CEMIP promoted migration and invasion in SCLC and applied proteomics analysis to screen out potential target profiles and the signaling pathway related to CEMIP regulation. Immunofluorescence was conducted to exam the expression of CEMIP on SCLC and paired adjacent normal tissues among enrollment. RT-qPCR and Western blot (WB) assays were conducted to valuate cellular protein and mRNA expression of CEMIP and EMT markers. Lentivirus-CEMIP-shRNAs and CEMIP plasmid were used for expression manipulating. Changes of cellular migration and invasion were tested through transwell assays. Tandem Mass Tag (TMT) peptide labeling coupled with LC–MS/MS was used for quantifying proteins affected by reducing expression of CEMIP on H446 cells. The expression of CEMIP showed 1.64 ± 0.16-fold higher in SCLC tissues than their normal counterpart. Decreasing the expression of CEMIP on SCLC cells H446 regressed both cellular migration and invasion ability, whereas the promoting cellular migration and invasion was investigated through over-expressing CEMIP on H1688. Proteomic and bioinformatics analysis revealed that total 215 differentially expressed proteins (DEPs) that either their increasing or decreasing relative expression met threshold of 1.2-fold changes with p value ≤ 0.05. The dramatic up-regulated DEPs included an unidentified peptide sequence (encoded by cDNA FLJ52096) SPICE1 and CRYAB, while the expression of S100A6 was largely down-regulated. DEPs mainly enriched on caveolae of cellular component, calcium ion binding of biological process and epithelial cell migration of molecular function. KEGG enrichment indicated that DEPs mainly exerted their function on TGF-β, GABAergic synapse and MAPK signaling pathway. It is the first report illustrating that CEMIP might be one of the metastatic triggers in SCLC. And also, it provided possible molecular mechanism cue and potential downstream target on CEMIP-induced cellular migration and invasion on SCLC.

Background Abnormalities in the KEPA1-NRF2 pathway have a role in cancer progression, metastasis, and resistance to chemo- and radiotherapies. Persistent activation of NRF2 associates with poor prognosis across different cancer types. However, the beneficial therapeutic strategy to harness this pathway in cancer remains unclear. This study aimed to investigate the clinical outcome with immunotherapy in NFE2L2/KEAP1 mutant population. Materials and Methods We investigated the correlation between NFE2L2/KEAP1 mutations and tumor mutational burden (TMB) and programmed death-ligand 1 (PD-L1) expression status to identify the therapeutic vulnerability. For this purpose, relevance analysis with TMB value was performed in 9,040 patients with cancer, and relevance analysis with PD-L1 expression was performed in 3,457 patients. The Memorial Sloan Kettering Cancer Center (MSKCC) database and real-world evidence were used to assess the immunotherapy response in NFE2L2/KEAP1 mutant subsets. Results NFE2L2/KEAP1 mutations occurred in various cancers, and the highest mutation incidences occurred in lung squamous cell carcinoma (LUSC) at 19.16% (NFE2L2) and 10.31% (KEAP1). We confirmed that higher TMB value and PD-L1 expression were associated with NFE2L2/KEAP1 mutations compared with wild-type, especially in non-small lung cancer. MSKCC database analysis showed the improved survival of patients with NFE2L2/KEAP1 mutant with immunotherapy compared with other treatments (median overall survival 22.52 VS 12.89, p = .0034). Real-world evidence further confirmed the efficacy of immunotherapy in the mutant population. Conclusion Our study revealed that patients with NFE2L2/KEAP1 mutant could achieve improved outcomes from immunotherapy than the other treatments. These findings may broaden the application of immune checkpoint blockade to patients harboring NFE2L2/KEAP1 mutations. Implications for Practice NFE2L2/KEAP1 alterations occur frequently in multiple cancer types and are associated with poor prognosis; however, the efficacious strategy to inhibit this pathway in cancer is poorly understood. This study was designed to analyze the mutational characteristics of NFE2L2/KEAP1 alterations in 9,243 Chinese patients. The highest mutation incidences occurred in lung squamous cell carcinoma at 19.16% (NFE2L2) and 10.31% (KEAP1). Relevance analysis showed the NFE2L2/KEAP1 mutant subsets were associated with higher tumor mutational burden value and programmed death-ligand 1 expression. Clinical data further confirmed NFE2L2/KEAP1 mutations correlate with improved outcome with immunotherapy. These findings suggest the clinical application of immunotherapy in the NFE2L2/KEAP1 mutant population.

Background: Lung Cancer, predominantly non-small-cell lung cancer (NSCLC), is the leading cause of cancer-related death in China. Although precision therapies for patients with advanced or metastatic NSCLC have developed over the past two decades, the 5-year survival rate remains low at 0%-26%. Thus, recurrence monitoring and treatment at an early stage are of great significance for improving survival benefits. Here, we explored the genetic characteristics of early stage NSCLC patients to provide additional values to predict recurrence risk and treatment strategies. Methods: Tumor or plasma samples were collected from 146 Chinese NSCLC patients in stage I-III (127 LUAD, 5 LUSC, 2 LUASC, 12 unknown pathology). 733 cancer-related genes were sequenced on NGS platform for variants analysis. Tumor mutation burden (TMB) was defined by all somatic mutation counts in coding region per megabase. Immunohistochemistry (IHC) was performed using antibodies (clone 22C3 or SP263) to analyze PD-L1 expression. PD-L1 positivity was defined as TPS ≥1%. Online databases, such as cBioPortal, TIMER2.0 and Kaplan-Meier Plotter, were also used for analysis. Statistical analysis was performed using the R Software (v 4.0.5). Results: Of 146 NSCLC patients, commonly mutated genes were detected, including EGFR (68%), TP53 (40%), KMT2D (10%), MSH3 (9%), RBM10 (9%), ZFHX3 (9%). Six pathogenic or likely pathogenic fusion variants harbored in common driver genes like EGFR, ALK and ROS1 were identified for the first time. EGFR was more frequently mutated in female patients (P < 0.01), while CDH10 mutations occurred more often in male patients (P < 0.05). Correlation analysis showed RBM10, ZFHX3 and CTNNB1 mutations were respectively co-occurrent with CARD11, ARHGAP5 and APC, reflecting the distinct profile of our cohort when compared to cBioPortal. Patients with TP53mut, MSH3mut or LRP1Bmut had significantly higher TMB (P < 0.05). Compared to PD-L1- group, TP53, TIMELESS, FBXW7 were remarkably mutated in PD-L1+ group. In LUAD, SPTA1mut and TIMELESSmut were noticeably related to CD8+T and B cell infiltration, while FBXW7mut and ZFHX3mut with more M1 macrophages infiltration. Prognostic analysis showed that LUAD patients harboring MSH3mut (P < 0.001) and SPENmut (P = 0.0005) at stage II exhibited significantly shorter RFS. Moreover, we found that cases carried somatic mutations in TP53 signaling pathway had more lymph node metastasis. Conclusion: These findings expanded our understanding of the early stage Chinese NSCLC, hopefully providing valuable guidance for recurrence risk prediction and treatment strategies. Citation Format: Naiquan Mao, Weishen Yao, Liufu Su, Xiaochun Huang, mengli Huang. Genetic characteristics of the early stage Chinese NSCLC patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5739.

Background/Aims: Gap junctions, which are assembled by connexins, can directly connect the cytoplasm of adjacent cells and enable gap junctional intercellular communication (GJIC) as well as metabolic coupling between neighboring cells. Here, we investigated the role of connexin 43 (Cx43) and its derived GJIC in the interplay between non-small cell lung cancer (NSCLC) cells and cancer-associated fibroblasts (CAFs). Methods: CAFs and NSCLC cells were co-cultured with direct contact and separated using flow cytometry. Glucose uptake, lactate production, and the expression and activity of PKM-2 and LDH-A in sorted CAFs were measured by a colorimetric assay, western blotting, and enzyme-linked immunosorbent assay (ELISA). Meanwhile, E-cadherin and N-cadherin expression and the migration and invasion of sorted NSCLC cells were detected by western blotting, wound width, and Transwell assays. Pyruvate, acetyl-CoA, and citric acid levels, ATP levels, and LDH-B and α-KG activity in sorted NSCLC cells were determined by a colorimetric or fluorometric assay and ELISA, respectively. Functional GJIC between cells and the subcellular location of connexins were detected by a “Parachute” assay and immunofluorescence. Levels of α-SMA, Cx43, and LDH-B in tissue from patients with NSCLC were determined by immunohistochemistry. Results: Cx43 accumulated in the plasma membrane, which favored the assembly of asymmetric unidirectional GJIC from CAFs to NSCLC cells. CAFs underwent increased aerobic glycolysis and promoted the epithelial-mesenchymal transition, migration, and invasion of NSCLC cells. In contrast, NSCLC cells experienced enhanced oxidative phosphorylation upon CAF stimulation, with an increase in ATP generation and thereby activation of the PI3K/Akt and MAPK/ERK pathways. Metabolic coupling between CAFs and NSCLC cells was under the strict control of Cx43-formed unidirectional GJIC. Patients with high tri-expression of α-SMA, Cx43, and LDH-B had the shortest overall survival and relapse-free survival compared with those with individual overexpression or high bi-expression. Conclusion: Cx43-formed unidirectional GJIC plays a critical role in mediating close metabolic cooperation between CAFs and NSCLC cells to support the malignant progression of NSCLC.

NUT carcinoma (NC) is an aggressive squamous tumor characterized by NUT gene rearrangement, and the most common fusion form is BRD4-NUT. However, NC diagnosis is difficult for its rareness and often being confused with a variety of poorly differentiated tumors. A 21-year-old Chinese woman was referred to our hospital for cough and intermittent fever. Chest computed tomography (CT) imaging revealed a left lobe hilar mass. Fiberoptic bronchoscopy results showed that tumor cells were poorly differentiated. In combination with immunohistochemistry staining, she was misdiagnosed with Ewing’s sarcoma/primitive neuroectodermal tumor. Next-generation sequencing (NGS) revealing BRD4-NUT fusion, and NUT immunohistochemistry confirmed the diagnosis of NC. Subsequently, left pneumonectomy and lymph node dissection were performed, and the patient received pemetrexed and lobaplatin treatment. NGS technology played an important role in NC diagnosis in this case, and it may have clinical use for rare cancer diagnosis and guidance of potential targeted therapies.

The present study aimed to isolate and characterize side population (SP) cells in the human lung cancer A549 cell line, and elucidate the molecular mechanism of SP cells underlying lung cancer. The SP and non-SP (NSP) cells in A549 cells were isolated and their differentiation was analyzed by fluorescence-activated cell sorting. An in vitro plate clone assay, Matrigel® Transwell assay and chemoresistance analysis of the sorted SP and NSP cells were performed. In addition, the sorted SP and NSP cells were injected into BALB/c nude mice to detect their tumorigenic potential in vivo. The expression of ATP-binding cassette sub-family G member 2 (ABCG2) in transplanted tumors was detected by immunohistochemistry. The SP and NSP cells were successfully isolated. The results demonstrated that SP cells accounted for 1.09% of live A549 cells. SP cells produced SP and NSP cells, while NSP cells only produced NSP cells. In addition, SP cells formed more colonies, exhibited improved invasive ability and increased levels of chemoresistance compared with NSP cells in vitro. SP cells demonstrated a higher tumorigenic potential in BALB/c nude mice, and the number of ABCG2-positive cells in the SP xenograft tumors were significantly increased compared with that in the NSP xenograft tumors. The present study indicated that SP cells isolated from the human lung cancer A549 cell line demonstrated increased tumorigenicity, and improved invasive ability and chemoresistance compared with NSP cells. In addition, detection of ABCG2 expression may assist in predicting the chemotherapeutic outcome of patients, and serve as a target for treating lung cancer.

e20506 Background: Differentiation of multiple primary lung cancer (MPLC) from intrapulmonary metastasis (IPM) is critical to determine clinical stage. Although clinicopathological features could provide certain evidences, it’s still challenging to identify the tumor malignancy accurately. In General, standard histopathologic approach is adequate in most cases, but has notable limitations in the recognition of IPMs. Herein, we propose an integrated molecular algorithm to facilitate MPLCs and IPMs diagnosis in the clinical practice. Methods: 40 Chinese patients with lung adenocarcinomas were enrolled in the study, 84 tumor samples were collected for next-generation sequencing. Somatic alterations with variant allele fraction (VAF) ≥1% were taken into account for molecular algorithm. A genomic database of 2,471 Chinese lung adenocarcinomas (LUAD) was used to calculate odds of coincidental occurrence, prevalence of individual mutation prevalence. Tumor relatedness diagnosed by histopathologic assessment was contrasted with comparative genomic profiling by subsequent NGS. Moreover, the performance of molecular algorithm prediction was evaluated as well. Results: Firstly, we compared the performance of comprehensive next-generation sequencing (NGS) with standard histopathologic approaches for distinguishing NSCLC subtypes in clinical practice. The genomic profiling was described as following: EGFR alterations occurred more frequently in MPLCs compared to IPMs (77.1% vs 50.0%, P

This study aimed to evaluate the biological functions of excision repair cross complementation goup 1 (ERCC1) in cell proliferation, cell cycle, invasion and cisplatin response of non-small cell lung cancer (NSCLC) cells. Firstly, ERCC1 gene was successfully transfected into H1299 cells by gene cloning and transfection techniques. Then, cell proliferation was determined with the cell growth curve and colony-forming assays. Flow cytometry (FCM) was employed to investigate the cell cycle distribution. The ability of cell invasion was estimated by means of Matrigel invasion assays. Response of NSCLC cells to cisplatin was detected utilizing MTT assays, and the intracellular drug concentrations were determined by the high performance liquid chromatography (HPLC) analysis. Expression of the two cell membrane proteins, P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP), was also evaluated utilizing FCM technique. By contrast, ERCC1 expression in the NSCLC A549 cells was silenced by small interfering RNA (siRNA) through RNAi technique. In addition, the cytotoxic effect of cisplatin on A549 cells was detected by MTT assays. In the present study, the results demonstrated that ERCC1 had no effect on cell proliferation, cell cycle and the ability of invasion, but showed significant impact on cisplatin response of the NSCLC H1299 cells. Furthermore, siRNA-induced suppression of ERCC1 evidently enhanced sensitivity to cisplatin of NSCLC A549 cells. Therefore, it is confirmed that ERCC1 is a chemotherapy-tolerating gene and a promising predictor in tailoring chemotherapy of NSCLC.

Background: Characterization of genomic alterations that drive patient disease development is critical in cancer management. The genomic alteration and population characteristics between the primary tumors and metastases in patients with non-small cell lung cancer (NSCLC) is still unclear. Here we evaluated the frequency and distribution of all classes of genomic alterations in both primary and metastatic NSCLC by comprehensive genomic profiling approach. Methods: FFPE tumor and matched blood samples of 1135 Chinese NSCLC patients (female:male is 670: 465), including 954 primary tumors and 181 metastases, were collected for next-generation sequencing (NGS) based panel assay. Gene copy number variations (CNV) including gene amplifications and deletions, short variants, and gene fusions were assessed. Results: On average, 0.65 gene copy number variations were detected in the 181 metastatic lesions, which is higher than 0.43 CNVs per sample in the primary lesions (p value is 0.003). No significant difference was found in short variants (2.48 vs 2.31), fusions (0.27 vs 0.20) and germline mutations (0.26 vs 0.31) between the primary and metastatic NSCLC. In the top-ranked genes with copy number alterations, EGFR amplifications were detected in 11% of the primary and 15% in metastases. MET amplifications, CDKN2A/B deletions, and PMS2 deletions were more frequently found in metastatic lesions: MET (7.7% vs 1.7%, p=0.0001), CDKN2A (5.5% vs 1.5%, p=0.002), CDKN2B (5.0% vs 1.9%, p=0.0007), and PMS2 (3.9% vs 1.2%, p=0.016). Conclusions: Copy number variations are common driver mutations in NSCLC. We reported here that the prevalence of copy number variations between primary and metastatic lung cancers was different, including driver genes MET, CDKN2A/B, and PMS2. No difference was observed in terms of frequency on short variants or gene fusions in NSCLC. Citation Format: Yunfei Shi, Naiquan Mao, Xiao Ding, Jianji Guo, Gang Guo, Zheng Chen, Weiguang Gu, Lei Dai, Shiwang Wen, Hui Jia, Ziqiang Tian, Junping Shi, Taiyan Guo, Jicheng Yao, Fei Pang, Gungwei Chirn, Ming Yao. Comparison of gene copy number variations (CNV) in primary and metastatic lung cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3391.

e13074Background: Lung cancer is the leading cause of death of all tumors in China. Due to imbalanced development of different provinces, the surgical treatments of NSCLC in different areas of Chin...

Ku70, Ku80 and DNA-PKcs proteins take part in the repairment of DNA double-strand breaks as regulatory subunits of DNA-dependent protein kinase. The aim of this study is to investigate the expression and clinical significance of Ku70, Ku80 and DNA-PKcs proteins in patients with stage I-II non-small cell lung cancer (NSCLC).A total of 86 patients with stage I-II NSCLC who received adjuvant chemotherapy after radical surgery were retrospectively analyzed. The expression of Ku70, Ku80 and DNA-PKcs proteins was detected by tissue microarray technique and immunohistochemical two-step method.The positive rate of Ku70, Ku80 and DNA-PKcs in lung cancer tissues was 68.6%, 72.1% and 87.2%, respectively. Their expression was not related to histological classification (P0.05). The patients with worse prognosis seemed to have higher expression of Ku70, Ku80 and DNA-PKcs proteins, however there was no statistical significance (P0.05).Ku70, Ku80 and DNA-PKcs are overexpressed in stage I-II lung cancer without prior chemotherapy. They may be not good for guidance of postoperative chemotherapy in completely resected stageI-II NSCLC.

To maximize the preservation of functional pulmonary parenchyma and improve the quality of life of patients with centrally located lung cancer, trachea-bronchoplasty has been used in clinical application with good efficacy. The aim of this study is to explore the appropriate admission and management of trachea-bronchoplasty and prevent complications of trachea-bronchial sleeve resection in the treatment of centrally located lung cancer.Seventy-six patients with central lung cancer, who were treated with trachea-bronchoplasty from June, 1988 to October, 2004, were analyzed. There were 49 cases of squamous cell carcinoma, 16 adenocarcinoma, 7 adenosquamous carcinoma, 3 small cell lung cancer and 1 adenoid cystic adenocarcinoma. Seventeen patients were in stage I, 39 in stage II, 17 in stage IIIA and 3 in stage IIIB. There were 55 cases of sleeve lobectomy, 12 lobectomy with wedge resection of the main bronchus, 8 big arc resection of superior lobar bronchus-main trachea-lateral wall of trachea, 1 resection of right upper lobe-right main bronchus-carina-lateral trachea and carinal reconstruction.Postoperative complications happened in 7 patients. Pneumonia and atelectasis occurred in 6 cases, in which 1 died of heart and respiratory failure. Another one died of haemorrhage of upside alimentary canal. Seventy-one patients were followed up (93.4%). The 1-, 3-, 5-year survival rate was 82.4% (56/68), 57.8% (26/45) and 41.7% (15/36) respectively.The trachea-bronchoplasty can not only preserve functional pulmonary parenchyma as much as possible and improve the quality of life of patients, but also provide an operative opportunity to those patients with poor pulmonary function in the treatment of centrally located lung cancer.