Development and validation of four ferroptosis-related gene signatures and their correlations with immune implication in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. This tumor presents with an insidious onset, rapid progression, and frequent recurrence. Ferroptosis is a newly discovered mode of programmed cell death that may play a key role in the progression of HCC. This study aimed to investigate the prognostic value of ferroptosis-related genes (FRGs) in HCC and their impact on tumor immune function, thereby providing new insights into targeted therapy for HCC. First, 43 differentially expressed FRGs were identified using the TCGA database, and four prognostically relevant methylation-driven FRGs (G6PD, HELLS, RRM2, and STMN1) were screened via survival and methylation analyses. Gene co-expression, mutation, and clinicopathological characterization indicated that these four pivotal FRGs play essential roles in tumor progression. We also validated these four genes using transcriptomic and proteomic data as well as cohort samples from our patients. Moreover, receiver operator characteristic (ROC) curves confirmed that the signatures of the four FRGs were independent prognostic factors in HCC. Gene set enrichment analysis of the four FRGs showed statistically significant associations with pathways related to HCC proliferation. Finally, the TIMER and TISIDB databases indicated that the four FRGs were statistically significantly correlated with tumor-infiltrating immune cells and immune checkpoint expression. Taken together, this study provides information guiding a novel therapeutic strategy targeting FRGs for HCC treatment.

Long noncoding RNA PITPNA-AS1 promotes cervical cancer progression through regulating the cell cycle and apoptosis by targeting the miR-876-5p/c-MET axis.

Cervical cancer is a common tumor type and a leading cause of tumor death among female in the world. However, the molecular mechanisms revealing the cervical cancer progression have not been fully investigated. Long noncoding RNA (LncRNA) PITPNA-AS1 is a newly found lncRNA, showing the promoting role in tumor growth. But its effects on cervical cancer development still remain unknown. In the study, we found that PITPNA-AS1 was markedly increased in human cervical cancer tissues and cell lines. PITPNA-AS1 over-expression elevated the proliferation of cervical cancer cells, whereas PITPNA-AS1 knockdown reduced the cell proliferation. Moreover, PITPNA-AS1 knockdown markedly accelerated the G0/G1 and reduced the G2/M phase transitions through decreasing the cyclin-dependent kinase (CDK)-2/4/6 and CyclinD1 expression levels. In addition, apoptosis was significantly induced by PITPNA-AS1 knockdown in cervical cancer cells. Importantly, PITPNA-AS1 was identified as the sponge of miR-876-5p, and a negative correlation was detected between PITPNA-AS1 and miR-876-5p in cervical cancer samples. Moreover, tyrosine-protein kinase MET (c-MET) was identified to be a down-streaming target gene of miR-876-5p in cervical cancer cells. PITPNA-AS1 meditated the effects of c-MET on the proliferation, apoptosis and cell cycle in cervical cancer cells by adsorbing miR-876-5p. In summary, targeting the PITPNA-AS1-associated signaling could be a therapeutic strategy for the treatment of cervical cancer.

Resistance to bevacizumab in ovarian cancer SKOV3 xenograft due to EphB4 overexpression.

AIM OF STUDY: Bevacizumab (BV) is broadly used to treat a number of cancers; however, BV resistance mechanisms and strategies to overcome this resistance are yet to be determined. MATERIALS AND METHODS: In this study, we used ovarian xenograft model to evaluate the underlying resistance mechanisms of BV in ovarian cancer treatment. RESULTS: Our results showed that EphB4 was overexpressed in BV-resistant xenograft models instead of other common receptor tyrosine kinases. In addition, when coadministrated with EphB4 blocker NVP-BHG712, the antitumor effect of BV was significantly enhanced in the resistant model, further confirmed the role of EphB4 in BV-resistant ovarian cancer. These results indicate that NVP-BHG712 reverses EphB4 overexpression-mediated resistance to BV. CONCLUSION: These findings represent a guide for the design of future medication strategy and may be useful in guiding the use of BV in combination with NVP-BHG712 in patients with resistance or intolerance ovarian cancer.

Suppressive efficiency of RASSF1A in endometrial carcinoma via inhabiting estrogen receptor alpha expression and ERK pathway activation.

INTRODUCTION: Known as a tumor suppressor, the Ras association domain family 1 isoform A (RASSF1A) is implicated in many human cancers, such as endometrial carcinoma. There is little known about the tumor inhibitive effects of RASSF1A on endometrial carcinoma. The present study was designed to investigate the role of RASSF1A in HEC-1-A cells and to explore its potential mechanisms. MATERIALS AND METHODS: In this study, overexpression of RASSF1A was established by transfection the recombinant adenoviral RASSF1A in HEC-1-A cells. Cells viability was assessed by MTT assay and the apoptosis was analyzed using flow cytometry. Cell migration and invasion were measured in Transwell assay. The levels of ERα and PELP1 protein and extracellular regulated protein kinase (ERK) pathway activation were detected by Western blot. RESULTS: RASSF1A over-expression could significantly inhibit the proliferation, migration and invasion of the HEC-1-A cells in transfection with RASSF1A group compared to that in transfection with control group, also induced apoptosis and suppressed the tumor growth after injection in nude mice. Moreover, overexpression of RASSF1A could inhibit the ERK signal pathway activation and decrease the ERα and PELP1 expression. CONCLUSION: Tumor suppressive efficiency of RASSF1A is exerted through the regulation of ERK pathway activation, ERα and PELP1 expression.

[Clinical Characteristics of Lung Cancer with Pancreatic Metastases].

BACKGROUND: Lacking of typical symptoms, more than 70% of patients with lung cancer are diagnosed as advanced-stage disease. Patients suffer from solid organs metastasis with different clinical features and prognosis. With development of new technology, more and more lung cancer patients are diagnosed with pancreatic metastasis. The aim of this study was to investigate clinicopathologic and survival difference by retrospective analysis among lung cancer patients with pancreatic metastases. METHODS: Of the patients with lung cancer diagnosed by pathology and thorough staging evaluation and treated at Beijing Cancer Hospital with long follow-up during July 1996 and June 2017, 35 cases had pancreatic metastases. RESULTS: There were 28 cases diagnosed as small cell lung cancer, 3 cases diagnosed as adenocarcinoma and 4 cases diagnosed as squamous cell carcinoma. There were 15 cases with pancreatic metastases in head of pancreas and 20 cases in body and tail of pancreas, 23 cases presented with isolated metastasis and 12 cases with multiple metastases. Pathological type was prognostic factor for lung cancer patients with pancreatic metastases. CONCLUSIONS: Pancreatic metastases represents an uncommon site of extrathoracic spread of disease for part of patients with advanced lung cancer. Lung cancer with pancreatic metastases should be treated by combined therapy, especially by systemic chemotherapy. Pathological type was prognostic factor for lung cancer patients with pancreatic metastases.
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5-Aminolevulinic acid photodynamic therapy in human cervical cancer via the activation of microRNA-143 and suppression of the Bcl-2/Bax signaling pathway.

5-Aminolevulinic acid photodynamic therapy (ALA­PDT) is a method using a photosensitizer and light radiation for disease treatment, and is currently used for the treatment of skin cancers, precancerous lesions and viral warts. The present study aimed to investigate the effect of ALA­PDT on human cervical cancer through the regulation of microRNA­143 (miR­143) and the Bcl-2/Bax signaling pathway. The results demonstrated that ALA­PDT reduced proliferation, increased cytotoxicity and induced apoptosis in HeLa human cervical carcinoma cells. Reverse transcription­quantitative polymerase chain reaction analysis demonstrated that the expression levels of miR­143 were increased following ALA­PDT treatment. Western blotting indicated that the expression levels of Bcl­2 and Bax were significantly reduced and increased, respectively, by ALA­PDT treatment. In addition, upregulation of miR­143 expression reduced Bcl­2 expression and increased Bax expression in HeLa cells. However, downregulation of miR­143 expression inhibited the effect of ALA­PDT on Bcl-2/Bax protein expression. In conclusion, the current study demonstrated that ALA­PDT affected human cervical cancer via the activation of miR-143 and the suppression of the Bcl-2/Bax signaling pathway.

Renal blood perfusion in GK rats using targeted contrast enhanced ultrasonography.

OBJECTIVE: To explore application of targeted contrast enhanced ultrasonography in diagnosis of early stage vascular endothelial injury and diabetic nephropathy. METHODS: Targeted SonoVue-TM microbubble was prepared by attaching anti-TM monoclonal antibody to the surface of ordinary microbubble SonoVue by biotin - avidin bridge method and ultrasonic instrument was used to evaluate the developing situation of targeted microbubble in vitro. Twenty 12-week-old male GK rats and 20 Wistar rats were enrolled in this study, and were randomly divided into targeted angiography group and ordinary angiography group. Targeted microbubbles SonoVue-TM or general microbubble SonoVue were rapidly injected to the rats via tail vein; the developing situation of the two contrast agents in rats kidneys was dynamically observed. Time-intensity curve was used to analyze rat kidney perfusion characteristics in different groups. RESULTS: Targeted ultrasound microbubble SonoVue-TM was successfully constructed, and it could be used to develop an external image. Targeted microbubbles SonoVue-TM enabled clear development of experimental rat kidney. Time-intensity curve shapes of rat kidney of the two groups showed as single apex with steep ascending and slowly descending branch. Compared with the control group, the rising slope of the GK rat renal cortex, medulla in targeted angiography group increased (P < 0.05); the peak intensity of medulla increased (P < 0.05), and the total area under the curve of medulla increased (P < 0.05). Compared with control group, the ascending branch of the GK rat in renal cortex, medulla in ordinary angiography group increased (P < 0.05). The peak intensity of the curve increased (P < 0.05), and the total area under the curve increased (P < 0.05). Compared with the ordinary angiography group, the peak of GK rat medulla curve in targeted angiography group intensity increased (P < 0.05), and the total area under the curve increased (P < 0.05). CONCLUSIONS: Targeted microbubbles SonoVue-TM can make a clear development of experimental rat kidney, its stable performance meet the requirement of ultrasonic observation time limit, and it can reflect early changes of blood perfusion in GK rat kindey.

[Characteristics and treatment of bone metastases in 322 cases non-small cell lung cancer: a retrospective study].

BACKGROUND: Bone metastases are the most common metastases of the non-small cell lung cancer (NSCLC). It can lead to bone ache and pathology fracture, deteriorate the quality of life. METHODS: We retrospectively investigated the characteristics, diagnosis and prognosis factors of bone metastases in NSCLC. All of the 600 patients are from department of thoracic oncology in recently 5 years. Emission computed tomography (ECT) was used to screen the bone metastases and the diagnosis of bone metastases was confirmed by computed tomography (CT)/magnetic resonance imaging (MRI)/X-ray or pathology. RESULTS: Among the total 322 bone metastases patients, subtype of adenocarcinoma had the most opportunity to occur bone metastases, and we found that vertebrae, pelvis and femora et al were the most frequently involved metastases sites. Patients who had more than 3 high 18F-FDG uptake sites of ECT, could be confirmed bone metastases by CT/MRI/X-ray than those with 1-2 high 18F-FDG uptake sites [80.6% (203/252) vs 50.79% (32/63), P<0.001]. The patients with bone metastases who had non-SRE had longer survival than that of SRE [1-yr survival 44.75% (non-SRE) vs 36.17% (SRE); median survival 14.74 mo (non-SRE) vs 12.25 mo (SRE)]. Multivariables analysis showed the pathology were non-adnocarcinoma, bone metastases less than 3 sites and bone metastases without other organs metastases would have good prognosis. CONCLUSIONS: There were relations between the numbers of abnormal dense sites of ECT and the diagnosis of skeletal metastases, non-adnocarcinoma bone metastases less than 3 sites and bone metastases without other organs metastases were the independent prognosis factors.

Epidermal growth factor receptor genotype in plasma DNA and outcome of chemotherapy in the Chinese patients with advanced non-small cell lung cancer.

BACKGROUND: The genotype of epidermal growth factor receptor (EGFR) is associated with tyrosine kinase inhibitor and effectiveness of therapy, but its role in cytotoxic chemotherapy is still unknown. Previous studies indicated that certain EGFR mutations were associated with response and progression free survival following platinum based chemotherapy. Our recent studies have identified that EGFR genotypes in the tumour tissues were not associated with response to the first-line chemotherapy in Chinese patients with advanced non-small cell lung cancer (NSCLC). In this study, we investigated associations of EGFR genotypes from plasma of patients with advanced NSCLC and response to first-line chemotherapy and prognosis. METHODS: We enrolled 145 advanced NSCLC patients who had received first-line chemotherapy in our department. We examined plasma EGFR genotypes for these patients and associations of EGFR mutations with response to chemotherapy and clinical outcomes. RESULTS: There were 54 patients with known EGFR mutations and 91 cases of wild types. No significant difference was detected in the response rate to first-line chemotherapy between mutation carriers and wild-type patients (37.0% vs. 31.9%). The median survival time and 1-, 2-year survival rates were higher in mutation carriers than wild-types (24 months vs. 18 months, 85.7% vs. 65.7% and 43.7% vs. 25.9%, P = 0.047). Clinical stage (IV vs. IIIb), response to the first-line chemotherapy (partial vs. no) and EGFR genotype were independent prognostic factors. CONCLUSION: Plasma EGFR mutations in the Chinese patients with advanced NSCLC is not a predictor for the response to first-line chemotherapy, but an independent prognostic factor indicating longer survival.

Potential clinical significance of a plasma-based KRAS mutation analysis in patients with advanced non-small cell lung cancer.

PURPOSE: Non-small cell lung cancer (NSCLC) with KRAS mutation may be resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). This study aims to evaluate a plasma-based KRAS mutation analysis and the clinical significance of plasma KRAS mutation as a predictive marker for tumor resistance to EGFR-TKIs in patients with NSCLC. EXPERIMENTAL DESIGN: DNA extracted from plasma and matched tumor tissues were obtained from 273 patients with advanced stage NSCLC. Patients were followed up prospectively for treatment outcomes. KRAS mutations in codon 12 and 13 were detected using PCR-restriction fragment length polymorphism. Mutations in plasma and matched tumors were compared. Associations between KRAS mutation status and patients' clinical outcomes were analyzed. RESULTS: KRAS mutation was found in 35 (12.8%) plasma samples and 30 (11.0%) matched tumor tissues. The consistency of KRAS mutations between plasma and tumors is 76.7% (23 of 30; kappa = 0.668; P < 0.001). Among 120 patients who received EGFR-TKI treatment, the response rate was only 5.3% (1 of 19) for patients with plasma KRAS mutation compared with 29.7% for patients with no KRAS mutation in plasma DNA (P = 0.024). The median progression-free survival time of patients with plasma KRAS mutation was 2.5 months compared with 8.8 months for patients with wild-type KRAS (P < 0.001). CONCLUSIONS: KRAS mutation in plasma DNA correlates with the mutation status in the matched tumor tissues of patients with NSCLC. Plasma KRAS mutation status is associated with a poor tumor response to EGFR-TKIs in NSCLC patients and may be used as a predictive marker in selecting patients for such treatment.

EGFR mutations are associated with prognosis but not with the response to front-line chemotherapy in the Chinese patients with advanced non-small cell lung cancer.

The study aimed to investigate associations of tumor tissue EGFR mutations with response to the front-line chemotherapy and prognosis in advanced non-small cell lung cancer (NSCLC) patients. EGFR genotypes of 145 chemotherapy-naive patients with Stage IIIB and IV NSCLC were examined by using denaturing high-performance liquid chromatography (DHPLC). All patients received the front-line chemotherapy. There were 69 patients who received gefitinib therapy (32 as second-line and 37 as third-line therapy). About 37.9% (55/145) of the patients was detected to have EGFR mutations in their tumor tissue DNA. The response rate (RR, complete response plus partial response) to the chemotherapy for mutated EGFR carriers was 34.5% (19/55), similar to 33.3% (30/90) for wild-type EGFR carriers (P=0.881). The patients with EGFR mutations had increased median survival time and 1- and 2-year survival rate than those with wild-type EGFR (23 vs 16 months, 86.38% vs 62.64%, 38.78% vs 27.16%, P=0.0273). Among Stage IV NSCLC patients, mutated EGFR carriers had a longer progression-free survival (PFS) than wild-type EGFR carriers (5 vs 3 months, P=0.040). Cox multivariate regression analysis showed that response to the front-line chemotherapy (RR vs PD) and EGFR mutation were independent prognostic factors (HR=0.461, 95% CI: 0.271-0.783, P=0.0042; HR=0.598, 95% CI: 0.372-0.961, P=0.0335, respectively) for patients with advanced NSCLC. We conclude that EGFR mutations in the Chinese patients with advanced NSCLC were not associated with response to the front-line chemotherapy, but Stage IV NSCLC patients with mutated EGFR had a longer PFS after the front-line chemotherapy. EGFR mutation is an independent prognostic factor for Chinese advanced NSCLC.

[A retrospective analysis: comparison of the clinical characteristics and prognosis in elderly and young patients with locally advanced or metastatic non-small cell lung cancer.].

OBJECTIVE: To investigate whether the clinical characteristics, treatment modalities and prognosis of elderly (>/= 70 years) patients with advanced non-small cell lung cancer (NSCLC) differed from those of young (

[The detection by denaturing high performance liquid chromatography of epidermal growth factor receptor mutation in tissue and peripheral blood from patients with advanced non-small cell lung cancer].

OBJECTIVE: To study the application of denaturing high performance liquid chromatography (DHPLC) as a screening tool in detecting plasma and matched tissue epidermal growth factor receptor (EGFR) mutations for advanced non-small-cell lung cancer (NSCLC). METHODS: Plasma DNA samples and matched tumors from 230 cases of NSCLC were analyzed for EGFR mutations in exons 19 and 21 using DHPLC. The mutations in the plasma samples and the matched tumors were compared, and the association between EGFR mutations and the clinicopathological features were evaluated. RESULTS: Mutation of EGFR was found by DHPLC to be 33.5% (77/230) in tissues and 34.3% (79/230) in matched peripheral blood samples. Consistency of EGFR mutation status between tissues and matched plasma DNA was confirmed (kappa is 0.74, P < 0.01). The sensitivity and specificity of DHPLC for detecting EGFR mutation were 96.9% and 91.9%, respectively (kappa is 0.88). EGFR mutations in both tissue and blood was correlated with histology type (OR = 3.38, 95% CI 1.81 - 6.36, P < 0.05) and smoking status (OR = 1.61, 95% CI 1.13 - 2.28, P < 0.05), but no association with age, sex and stage was found (P > 0.05). CONCLUSION: The detection of EGFR mutation is highly consistent in tissues and in plasma DNA samples. DHPLC may serve as a preliminary screening tool for detecting EGFR mutations.

[A phase II clinical trial of celecoxib combined with platinum-based chemotherapy in the treatment of patients with advanced NSCLC as first-line treatment.].

BACKGROUND: Currently, platinum-based regimes are standard first-line chemotherapy for non-small cell lung cancer. The aim of this study is to evaluate the efficacy, influencing factors and adverse events of celecoxib plus platinum-based chemotherapy in advanced non-small cell lung cancer as first-line treatment. METHODS: Previously untreated patients of advanced non-small cell lung cancer with COX-2 positive, confirmed by immunohistochemical staining, were randomized to receive GP, NP or TP regimens. Celecoxib of 400 mg Bid was given, po 5-7 days before chemotherapy,and not stopped until evidence of disease progression or toxicity. Adverse events were cirtified according to NCI-CTC criteria. Kaplan-Meier method was used to analyze the survival rate. COX regression was used to define the predictive factors. Primary endpoint: median survival time, 1-year survival rate and median progression free survival time. Secondary endpoint: response rate and toxicity. RESULTS: Forty-four evaluable patients were enrolled in the study from February 2005 to March 2007. Response rate was 45%, disease control rate 59%. Median progression free survival time and median survival time were 6months (95%CI: 4-8 months) and 18 months (95%CI: 9-27months), respectively. One-year survival rate was 68%. Numbers of chemotherapy cycles and overall evaluation were the predictive factors for PFS in COX model (P =0.023 and 0.000). No factor was defined to affect survival time. Neutropenia and nausea/vomit were the most common toxicity. CONCLUSIONS: Celecoxib combined with platinum-based chemotherapy appears to be well tolerated and demonstrates encouraging activity in patients of previously untreated advanced NSCLC.

[Distinguishing second primary tumors from lung metastasis in patients with postoperative non-small cell lung cancer by microsatellite analysis].

OBJECTIVE: In patients with resected early stage non-small cell lung cancer (NSCLC), intrapulmonary solitary tumor represents either second primary tumor (SPT) or a metastasis. This study is to discern SPT from lung metastasis in patients with postoperative NSCLC followed a solitary intrapulmonary tumor by microsatellite analysis. METHODS: Twenty-one patients with stage I - III(A) NSCLC resected by surgery during 1994.1 - 2002.8 were studied. Paired tumors from 21 patients with NSCLC and a solitary lung nodule were analyzed for their loss of heterozygosity (LOH) on chromosomal arms 3p, 9p and 17p. DNA from microdissected tumors and non-malignant lung tissues was subjected to polymerase chain reaction-based microsatellite analysis using 8 microsatellite markers. An effort was also made to distinguish SPT from lung metastasis on the basis of clinical and histopathologic features. RESULTS: The paired tumors from 7 patients had concordant patterns of LOH at all microsatellite loci suggesting the same clonal origin, and supporting metastatic spread, where 4 paired tumors had discordant patterns of at all loci suggesting independent tumor origin. These observations were supported by the clinical and pathologic findings. Additional 6 paired tumors had concordant allelic loss on 3p and discordant loss on the other, clinical characteristics supporting metastatic disease. In contrast, 2 paired tumors had concordant allelic loss on 9p or 17p but discordant loss on the 3p, clinical data supporting SPT. CONCLUSIONS: The paired tumors from 7 patients had concordant patterns of LOH at all microsatellite loci suggesting the same clonal origin, and supporting metastatic spread, where 4 paired tumors had discordant patterns of at all loci suggesting independent tumor origin. These observations were supported by the clinical and pathologic findings. Additional 6 paired tumors had concordant allelic loss on 3p and discordant loss on the other, clinical characteristics supporting metastatic disease. In contrast, 2 paired tumors had concordant allelic loss on 9p or 17p but discordant loss on the 3p, clinical data supporting SPT.

[Prognostic analysis of intrapulmonary metastasis for patients with non-small cell lung cancer].

BACKGROUND: It is well known that more than 40% patients were initially diagnosed with advanced non-small cell lung cancer (NSCLC) with intrapulmonary or/and distant metastasis. However, up to now, the reports about effects of different metastatic sites on survival were limited. The aim of this study is to investigate the clinicopathologic and survival difference by retrospective analysis among sole intrapulmonary metastasis, sole extrathoracic distant metastasis and simultaneous metastasis of lung and other extrathoracic organs for the patients with advanced NSCLC, and to analyze the prognosis-related factors of NSCLC with intrapulmonary metastasis. METHODS: Of the 425 patients with stage IV NSCLC diagnosed by pathology and through staging evaluation and treated at Beijing Cancer Hospital with long follow-up during Oct. 1995 to Dec. 2003, 81 cases had sole intrapulmonary metastasis, 98 cases had sole extrathoracic distant metastasis and 68 cases presented simultaneous lung metastasis and extrathoracic spread. Kaplan-Meier survival curve was performed to estimate the survival of patients with different metastasis, Log-Rank test was used to compare their survival difference, and univariate analysis was used to find prognostic related factors. RESULTS: Median survival time (MST) and 1-, 2-, 3-year survival rate (SR) for patients with sole intrapulmonary metastasis were 13 months (95% CI: 11-15), 57%, 21%, 7%, respectively; MST was 22 months (95% CI: 18-26) for patients with N1 and/or N2 and 10 months (95%CI: 7-13) for patients with N3 (P=0.001). Among the patients with ipsilateral, contralateral and bilateral intrapulmonary metastasis, difference of MST and 1-, 2-, 3-year SR had no statistical significance (P > 0.05); Survival of patients with sole intrapulmonary metastasis was not significantly different from that of patients with sole brain or bone metastasis (P > 0.05), but was longer than that of patients with simultaneous lung and extrathoracic spread (P=0.021). One way analysis of variance showed that no significant association were found among age, pathologic subtype, differentiation degree or response of first-line chemotherapy and survival of the patients with sole intrapulmonary metastasis (P > 0.05), but sex and invasive status of lymph node (N1/N2 vs N3) were found to influence the survival of the patients (P= 0.018, P=0.001). Further stratified analysis by age showed that invasion of lymph node was independent prognostic factor (P=0.002); whereas for the patients with simultaneous metastasis of lung and distant organs, metastatic numbers (2 vs ≥3) of organ were independent prognostic factor (P=0.013). CONCLUSIONS: No statistical difference is found among survival of NSCLC patients with sole intrapulmonary metastasis and with sole brain, bone metastasis. Invasive status of lymph node and metastatic number of organ are important prognostic factors for patients with sole intrapulmonary metastasis and simultaneous metastasis of lung and extrathoracic organs, respectively.