Objective:To assess prognostic factors and validate the effectiveness of recursive partitioning analysis (RPA) classes and graded prognostic assessment (GPA) in 290 non-small cell lung cancer (NSCLC) patients w...Objective:To assess prognostic factors and validate the effectiveness of recursive partitioning analysis (RPA) classes and graded prognostic assessment (GPA) in 290 non-small cell lung cancer (NSCLC) patients with brain metastasis (BM).Methods:From Jan 2008 to Dec 2009,the clinical data of 290 NSCLC cases with BM treated with multiple modalities including brain irradiation,systemic chemotherapy and tyrosine kinase inhibitors (TKIs) in two institutes were analyzed.Survival was estimated by Kaplan-Meier method.The differences of survival rates in subgroups were assayed using log-rank test.Multivariate Cox's regression method was used to analyze the impact of prognostic factors on survival.Two prognostic indexes models (RPA and GPA) were validated respectively.Results:All patients were followed up for 1-44 months,the median survival time after brain irradiation and its corresponding 95% confidence interval (95% CI) was 14 (12.3-15.8) months.1-,2-and 3-year survival rates in the whole group were 56.0%,28.3%,and 12.0%,respectively.The survival curves of subgroups,stratified by both RPA and GPA,were significantly different (P0.001).In the multivariate analysis as RPA and GPA entered Cox's regression model,Karnofsky performance status (KPS) ≥ 70,adenocarcinoma subtype,longer administration of TKIs remained their prognostic significance,RPA classes and GPA also appeared in the prognostic model.Conclusion:KPS ≥70,adenocarcinoma subtype,longer treatment of molecular targeted drug,and RPA classes and GPA are the independent prognostic factors affecting the survival rates of NSCLC patients with BM.展开更多
Although non-small cell lung cancer (NSCLC) can metastasize to almost any organ, metastasis to the gallbladder with significant clinical manifestation is relatively rare. Here, we report a case of gallbladder metast...Although non-small cell lung cancer (NSCLC) can metastasize to almost any organ, metastasis to the gallbladder with significant clinical manifestation is relatively rare. Here, we report a case of gallbladder metastasis of NSCLC presenting as acute cholecystitis. A 79-year-old man presented with pain in the right upper quadrant and fever. A computed tomography (CT) scan of the chest and abdomen showed a cavitary mass in the right lower lobe of the lung and irregular wall thickening of the gallbladder. Open cholecystectomy and needle biopsy of the lung mass were performed. Histological examination of the gallbladder revealed a moderately-differentiated squamous cell carcinoma displaying the same morphology as the lung mass assessed by needle biopsy. Subsequent immunohistochemical examination of the gallbladder and lung tissue showed that the tumor cells were positive for P63 but negative for cytokeratin 7, cytokeratin 20 and thyroid transcription factor-1. A second primary tumor of the gallbladder was excluded by immunohistochemical methods, and the final pathological diagnosis was gallbladder metastasis of NSCLC. Although the incidence is extremely rare, acute cholecystitis can occur in association with lung cancer metastasis to the gallbladder.展开更多
Objective The brain is the main site of failure in cancer patients with epidermal growth factor receptor(EGFR)mutations undergoing treatment.However,identifying patients who may develop brain metastases(BM)is difficul...Objective The brain is the main site of failure in cancer patients with epidermal growth factor receptor(EGFR)mutations undergoing treatment.However,identifying patients who may develop brain metastases(BM)is difficult.Autophagy is critical for cancer initiation and progression.We hypothesized that genetic variants in autophagy core genes might contribute to BM risk of non-small cell lung cancer(NSCLC)following treatment with EGFR tyrosine kinase inhibitor(EGFR-TKIs).Methods We systematically examined 16 potentially functional genetic polymorphisms in seven autophagy core genes among 105 TKI-treated NSCLC patients.Kaplan-Meier curves were plotted to assess the cumulative BM probability.Univariate and multivariate Cox proportional hazard regression analyses were utilized to calculate hazard ratios(HRs)and 95%confidence intervals(CIs).We evaluated the potential associations of these genes with subsequent BM development.Results We found that ATG16L1:rs2241880,ATG10:rs10036653,rs3734114,and ATG3:rs7652377 are significantly associated with NSCLC treated with EGFR-TKIs(all P<0.05).BM developed more often in patients with ATG3 rs7652377 CC genotype(33%),ATG10 rs10036653 AA genotype(43%),ATG10:rs3734114 CT/CC genotype(46%),and ATG16L1 rs2241880 AA genotype(37%)compared to patients with AA genotypes at rs7652377(12%),AT/TT genotypes at rs10036653(16%),the TT genotype at rs3734114(13%),or AG/GG genotypes at rs2241880(17%).Conclusion These associations may be critical for understanding the role of autophagy in BM risk.Future prospective studies are needed to determine if prophylactic cranial irradiation(PCI)could offer a survival benefit in this group of patients.展开更多
Objective: The aim of this study is to compare the effectiveness of surgery with stereotactic radiosurgery (SRS) for patients with a single synchronous brain metastasis from successfully treated non-small cell lung...Objective: The aim of this study is to compare the effectiveness of surgery with stereotactic radiosurgery (SRS) for patients with a single synchronous brain metastasis from successfully treated non-small cell lung cancer. Methods: Between 1995 and 2002, 53 patients underwent resection of both primary non-small cell lung cancer and the associated single brain metastasis. There were 33 men and 20 women with a mean age of 57 years (range, 32-85 years). At the time of diagnosis, 42 patients experienced lung cancer related symptoms, whereas 11 patients experienced brain metastases-related symptoms. 42 patients had received thoracic surgery first, and 11 patients had undergone neurosurgery or radiosurgery first. Pneumonectomy was performed in 9 out of 42 patients (21.4%), lobectomies in 30 (71.4%), and wedge resection in 3 (7.2%). 48 patients (90.5%) underwent complete lymphadenectomy. 35 patients underwent brain metastasectomy. 18 underwent SRS. Results: There was no postoperative mortality and severe complications after either lung or brain surgery. Histology showed 34 adenocarcinomas, 16 squamous cell carcinomas, and 3 large cell lung cancers. 15 patients (28.3%) had no evidence of lymph node metastases (No), 20 patients (37.7%) had hilar metastases (N1), and 18 patients (34%) had mediastinal metastases (N2). The 1-, 2-, 3- and 5-year overall survival rates were 49%, 19%, 10%, and 5%, respectively. The corresponding data for neurosurgery group were 55%, 17%, 11%, and 6%, respectively. The median survival time was 13 months. For SRS group the corresponding data were 44.8%, 20.9% 10.5%, and 2%, respectively. The median survival time was 14 months. The differences between the two groups were not significant (P〉0.05). In lymph node negative patients (No), the overall 5-year survival rate was 10%, as compared with a 1% survival rate in patients with lymph node metastases (N1-2). The difference was significant (P〈0,01). For adenocarcinomas, the 5-year survival rate was 5%. The correspondent data for squamous cell lung cancers was 3%. The difference was not significant (P〉0.05). Conclusion: Although the overall survival rate for patients who have brain metastases from NSCLC is poor, surgical resection or radiosurgery may be beneficial in a select group of patients with synchronous brain metastases and lung cancer without lymph node metastases.展开更多
BACKGROUND The presence of liver metastasis(LM) is an independent prognostic factor for shorter survival in non-small cell lung cancer(NSCLC) patients.The median overall survival of patients with involvement of the li...BACKGROUND The presence of liver metastasis(LM) is an independent prognostic factor for shorter survival in non-small cell lung cancer(NSCLC) patients.The median overall survival of patients with involvement of the liver is less than 5 mo.At present,identifying prognostic factors and constructing survival prediction nomogram for NSCLC patients with LM(NSCLC-LM) are highly desirable.AIM To build a forecasting model to predict the survival time of NSCLC-LM patients.METHODS Data on NSCLC-LM patients were collected from the Surveillance,Epidemiology,and End Results database between 2010 and 2018.Joinpoint analysis was used to estimate the incidence trend of NSCLC-LM.Kaplan-Meier curves were constructed to assess survival time.Cox regression was applied to select the independent prognostic predictors of cancer-specific survival(CSS).A nomogram was established and its prognostic performance was evaluated.RESULTS The age-adjusted incidence of NSCLC-LM increased from 22.7 per 1000000 in 2010to 25.2 in 2013,and then declined to 22.1 in 2018.According to the multivariable Cox regression analysis of the training set,age,marital status,sex,race,histological type,T stage,metastatic pattern,and whether the patient received chemotherapy or not were identified as independent prognostic factors for CSS(P < 0.05) and were further used to construct a nomogram.The C-indices of the training and validation sets were 0.726 and 0.722,respectively.The results of decision curve analyses(DCAs) and calibration curves showed that the nomogram was well-discriminated and had great clinical utility.CONCLUSION We designed a nomogram model and further constructed a novel risk classification system based on easily accessible clinical factors which demonstrated excellent performance to predict the individual CSS of NSCLC-LM patients.展开更多
Objective:To investigate the relationship between postoperative metastasis and circulating levels of osteopontin in non-small cell lung cancer(NSCLC).Methods:The expression of osteopontin mRNA were detected with R...Objective:To investigate the relationship between postoperative metastasis and circulating levels of osteopontin in non-small cell lung cancer(NSCLC).Methods:The expression of osteopontin mRNA were detected with RT-PCR technique.The circulating levels of osteopontin were measured through ELASA in 46 NSCLC cases that had not been received any anti-cancer treatment at the time of sampling.The tissues from fifteen patients with benign pulmonary diseases were studied as control group.Results:The overall median mRNA expression level of osteopontin was approximately 70-fold higher in tumor tissues than in matched normal lung tissues(P0.001).Over-expression of osteopontin mRNA was significantly associated with clinical stage(P=0.009).Advanced disease states had higher circulating level of osteopontin(stage I+II versus stage III+VI).In multivariate analysis,stage was the only independent factor influencing circulating levels of osteopontin.All patients were followed up for 12 months,2 of the 46 patients with both osteopontin mRNA expression and elevated plasma osteopontin levels had local recurrence and 10 had distant metastasis.There was a significant difference in the osteopontin levels between metastasis group and non-metastasis group.Conclusion:Preoperative plasma levels of osteopontin are significantly associated with post-operative metastasis in advanced NSCLC.展开更多
INTRODUCTION Non-small cell lung cancer(NSCLC)is a common malignant disease with an extremely poor prognosis.Lung cancer has been reported to metastasize to the eye in 0.2%to7%of patients based on clinical studies,a...INTRODUCTION Non-small cell lung cancer(NSCLC)is a common malignant disease with an extremely poor prognosis.Lung cancer has been reported to metastasize to the eye in 0.2%to7%of patients based on clinical studies,and in 6%to 7%of patients based on postmortem histopathologic studies.展开更多
Objective The aim of this study was to explore the mechanism behind lncRNA small nucleolar RNA host gene 19(lncRNA SNHG19)/microrNA-299-5P(miR-299-5p)/mitogen-activated protein kinase 6(MAPK6)signaling axis promoting ...Objective The aim of this study was to explore the mechanism behind lncRNA small nucleolar RNA host gene 19(lncRNA SNHG19)/microrNA-299-5P(miR-299-5p)/mitogen-activated protein kinase 6(MAPK6)signaling axis promoting metastasis of non-small cell lung cancer(NSCLC).Methods To analyze the abnormal expression of lncRNAs in NSCLC,50 surgically resected NSCLC and adjacent tissue samples were collected from August 2021 to August 2022.The mRNA expression levels of lncRNA SNHG19,Mir-299-5p,and MAPK6 were detected by qRT-PCR.The functions of lncRNA SNHG19,Mir-299-5p and MAPK6 were investigated by CCK-8,clone formation,EdU,scratch,Transwell western blotting(WB)and in vivo xenograft assay.RNA fluorescence in-situ hybridization(FISH),RNA pull-down,dual luciferase reporter,and RNA co-immunoprecipitation assays were used to explore the mechanism of action between lncRNA SNHG19,miR-299-5p,and MAPK6.Results High expression of lncRNA SNHG19 was correlated with poor prognosis,tumor size,lymph node metastasis,and TNM stage in NSCLC patients(P<0.05).Cell function experiments showed that lncRNA SNHG19 could improve the proliferation,clone formation,migration,and invasion ability of A549 cells both in vitro and in vivo(all P<0.05)and increased the relative expression levels of vimentin and MAPK6(P<0.05).The relative expression level of E-cadherin was decreased(P<0.05).lncRNA SNHG19 can interact with Mir-299-5p and regulate the expression level of MAPK6.Conclusion lncRNA SNHG19 is upregulated in NSCLC tissues and cells,and its high expression is associated with tumor progression and poor survival.Moreover,it can act as a molecular sponge for Mir-299-5p to regulate MAPK6 expression and promote the proliferation and metastasis of A549 cells.展开更多
Objective To study the risk factors of mediastinal lymph node metastasis in patients with ≤3 cm peripheral non small cell lung cancer. Methods From January 2000 to December 2010,a total of 281 patients with NSCLC [15...Objective To study the risk factors of mediastinal lymph node metastasis in patients with ≤3 cm peripheral non small cell lung cancer. Methods From January 2000 to December 2010,a total of 281 patients with NSCLC [152 men and 129 women,aged (60. 31 ± 12. 13) years; ≤ 3 cm in diameter]underwent lobectomy or partial resection with systematic mediastinal lymphadenectomy in hospital. Clinical data included age,gender,展开更多
To study the effect of IL-18 and nitric oxide(NO) on the growth and metastasis of non-small cell lung cancer (NSCLC).Methods Serum IL-18 and nitrate and nitrite levels in 82 patients with NSCLC and 20 healthy control ...To study the effect of IL-18 and nitric oxide(NO) on the growth and metastasis of non-small cell lung cancer (NSCLC).Methods Serum IL-18 and nitrate and nitrite levels in 82 patients with NSCLC and 20 healthy control subjects were measured by using ELISA and Griess.Results The levels of serum IL-18 were (334.2±31.0)ng/L in NSCLC patients and (151.3±22.0)ng/L in control subjects,respectively.The levels of nitrate and nitrite were (237.1±21.0)μmol/L in NSCLC patients and (44.2±15.0)μmol/L in control subjects.The levels of serum IL-18 and nitrate and nitrite were not related with age,gender,histological types in patients with NSCLC.The levels of serum IL-18 was closely associated with TNM stage,lymph node metastasis and distal metastasis,but not with its degree and organ types of metastasis.There was a negative correlation between the levels of serum IL-18 and nitrate and nitrite.Conclusion Serum IL-18 and nitrate and nitrite levels may be useful to evaluate the prognosis of the patients with NSCLC.16 refs,2 tabs.展开更多
Postoperative recurrence occurs in approximately half of patients with non-small cell lung cancer(NSCLC), even after complete resection. Disease recurrence after surgical resection reduces the patient's life expec...Postoperative recurrence occurs in approximately half of patients with non-small cell lung cancer(NSCLC), even after complete resection. Disease recurrence after surgical resection reduces the patient's life expectancy sharply. The prognosis after postoperative recurrence is considered to largely depend on both the mode of first recurrence(distant, locoregional or combined) and the treatment modality:(1) The majority of cases of postoperative recurrence involve distant metastasis with or without locoregional recurrence. Platinum-based systemic chemotherapy is practically accepted as the treatment for these diseases on the basis of evidence for original stage Ⅳ disease. The advent of both pemetrexed and molecular-targeted drugs has improved the survival of nonsquamous NSCLC and changed the chemotherapeutic algorithm for NSCLC;(2) Among patients with distant metastatic recurrence without locoregional recurrence at the primary tumor site, the metastasis is often limited in both organ and number. Such metastases are referred to as oligometastases. Local therapy, such as surgical resection and radiotherapy, has been suggested to be the first-line treatment of choice foroligometastatic recurrence; and(3) While locoregional recurrence is likely to cause troublesome symptoms, it is a potentially limited disease. Therefore, providing local control is important, and radiation is usually beneficial for treating local recurrence. In order to obtain better control of the disease and provide treatment with curative intent in patients with limited disease, the administration of concurrent platinum-based chemoradiotherapy is recommended according to the results of originally nonresectable stage ⅢA and ⅢB disease.展开更多
Lung cancer is the leading cause of cancer-related mortality throughout the world. Non-small cell lung cancer(NSCLC) accounts for 85% of all diagnosed lung cancers. Despite considerable progress in the diagnosis and t...Lung cancer is the leading cause of cancer-related mortality throughout the world. Non-small cell lung cancer(NSCLC) accounts for 85% of all diagnosed lung cancers. Despite considerable progress in the diagnosis and treatment of the disease, the overall 5-year survival rate of NSCLC patients remains lower than 15%. The most common causes of death in lung cancer patients are treatment failure and metastasis. Therefore, developing novel strategies that target both tumour growth and metastasis is an important and urgent mission for the next generation of anticancer therapy research. Heat shock proteins(HSPs), which are involved in the fundamental defence mechanism for maintaining cellular viability, are markedly activated during environmen-tal or pathogenic stress. HSPs facilitate rapid cell division, metastasis, and the evasion of apoptosis in cancer development. These proteins are essential players in the development of cancer and are prime therapeutic targets. In this review, we focus on the current understanding of the molecular mechanisms responsible for HLJ1's role in lung cancer carcinogenesis and progression. HLJ1, a member of the human HSP 40 family, has been characterised as a tumour suppressor. Research studies have also reported that HLJ1 shows promising dual anticancer effects, inhibiting both tumour growth and metastasis in NSCLC. The accumulated evidence suggests that HLJ1 is a potential biomarker and treatment target for NSCLC.展开更多
Objective: To investigate the expression characteristics of Livin and second mitochondrial activator of Caspase (Smac) proteins in non-small cell lung cancer (NSCLC), and analyze their effect on patients' progno...Objective: To investigate the expression characteristics of Livin and second mitochondrial activator of Caspase (Smac) proteins in non-small cell lung cancer (NSCLC), and analyze their effect on patients' prognosis. Methods: The expressions of Livin and Smac proteins were detected in 89 NSCLC tissue samples and 25 normal lung tissue samples by immunohistochemical technique. Results: The positive expression rates of Livin and Smac proteins in NSCLC tissues were 53.9%, and 58.4% respectively, higher than that in normal lung tissues(P〈0.01). Livin protein expression correlated with Smac protein significantly(Χ^2=1 8.451, P=0.000, r=0.455). The expression level of Livin protein was closely related to lymph node metastasis, TNM stage and histological type (P〈0.05), but not to sex, age, differentiation grade (P〉0.05). The expression level of Smac protein was closely related to lymph node metastasis, TNM stage (P〈0.01), but not to sex, age, histological types (P〉0.05). Kaplan-Meier analysis revealed a significant impact on survival by Livin protein in NSCLC (P〈0.01), but not by Smac protein (P〉0.05). Conclusion: Overexpression of Livin protein may play a promoting role in the occurrence and progression of NSCLC. Moreover, it may bring an adverse effect on patients' prognosis. Although overexpression of Smac protein affects the occurrence and progression of NSCLC, it has no relationship with the prognosis. Livin protein may be helpful to evaluate the progression of NSCLC, and to predict the prognosis.展开更多
Liver metastases(LMs)are common in lung cancer.Despite substantial advances in diagnosis and treatment,the survival rate of patients with LM remains low as the immune-suppressive microenvironment of the liver allows t...Liver metastases(LMs)are common in lung cancer.Despite substantial advances in diagnosis and treatment,the survival rate of patients with LM remains low as the immune-suppressive microenvironment of the liver allows tumor cells to evade the immune system.The impact of LMs on the outcomes of immune checkpoint inhibitors in patients with solid tumors has been the main focus of recent translational and clinical research.Growing evidence indicates that the hepatic microenvironment delivers paracrine and autocrine signals from non-parenchymal and parenchymal cells.Overall,these microenvironments create pre-and post-metastatic conditions for the progression of LMs.Herein,we reviewed the epidemiology,physiology,pathology and immunology,of LMs associated with non-small cell lung cancer and the role and potential targets of the liver microenvironment in LM in each phase of metastasis.Additionally,we reviewed the current treatment strategies and challenges that should be overcome in preclinical and clinical investigations.These approaches target liver elements as the basis for future clinical trials,including combinatorial interventions reported to resolve hepatic immune suppression,such as immunotherapy plus chemotherapy,immunotherapy plus radiotherapy,immunotherapy plus anti-angiogenesis therapy,and surgical resection.展开更多
Lung cancer metastasis is typically determined by histologic similarity between distant and primary lesions. Herein, we present a 70-year-old Japanese woman with an adenocarcinoma in her lung and a squamous cell carci...Lung cancer metastasis is typically determined by histologic similarity between distant and primary lesions. Herein, we present a 70-year-old Japanese woman with an adenocarcinoma in her lung and a squamous cell carcinoma in her femur; both tumors had an identical epidermal growth factor receptor mutation, G719 S. This indicated that both tumors had a common origin, despite their histologic dissimilarity. The tumor in the femur was thus identified genetically as a lung cancer metastasis. This case suggests that genetic analysis can determine whether a distant lesion is a lung cancermetastasis, particularly when the histology differs from that of the primary lesion.展开更多
Background:Immune checkpoint inhibitors(ICIs)are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer(NSCLC)harboring no actionable mutations;however,data on their efficacy amo...Background:Immune checkpoint inhibitors(ICIs)are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer(NSCLC)harboring no actionable mutations;however,data on their efficacy among patients presenting with intracranial lesions are limited.This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis.Methods:Our study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable,asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1,2019 and September 30,2021.The patients were stratified into two groups according to the first-line treatment regimen received:ICI combined with chemotherapy(n=102)or chemotherapy(n=109).Systemic and intracranial objective response rates(ORRs)and progression-free survival(PFS)were analyzed.Adverse events were also compared between the groups.Results:Compared with the chemotherapy-based regimen,the ICI-containing regimen was associated with a significantly higher intracranial(44.1%[45/102]vs.28.4%[31/109],χ^(2)=5.620,P=0.013)and systemic(49.0%[50/102]vs.33.9%[37/109],χ^(2)=4.942,P=0.019)ORRs and longer intracranial(11.0 months vs.7.0 months,P<0.001)and systemic(9.0 months vs.5.0 months,P<0.001)PFS.Multivariable analysis consistently revealed an independent association between receiving ICI plus platinum-based chemotherapy as a first-line regimen and prolonged intracranial PFS(hazard ratio[HR]=0.52,95%confidence interval[CI]:0.37-0.73,P<0.001)and systemic PFS(HR=0.48,95%CI:0.35-0.66,P<0.001).No unexpected serious adverse effects were observed.Conclusion:Our study provides real-world clinical evidence that ICI combined with chemotherapy is a promising first-line treatment option for driver gene mutation-negative advanced NSCLC patients who present with brain metastasis at initial diagnosis.Clinical trial registration:https://www.clinicaltrials.gov/,OMESIA,NCT05129202.展开更多
Background: As a novel molecular markerof non-small cell lung cancer (NSCLC), PRDI-BFI and R1Z homology domain containing protein 14 (PRDM 14) is over-expressed ill NSCLC tumor tissues. Extracellular matrix degra...Background: As a novel molecular markerof non-small cell lung cancer (NSCLC), PRDI-BFI and R1Z homology domain containing protein 14 (PRDM 14) is over-expressed ill NSCLC tumor tissues. Extracellular matrix degradation mediated by the balance between matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) is one of the most important mechanism in king cancer metastasis. This study aimed to determine if PRDM14 promoted the migration of NSCLC cells through extracellular matrix degradation mediated by change of MMP/TIMP expression. Methods: The expression of PRDM 14 was down-regulated in human cell line A 549 after transfection with lentiviral vector-mediated short-hairpin ribonucleic acids (shRNAs) which targeted the PRDM 14 promoter. Cellular migration ofshRNA-infected cells was detected by a scratch wound healing assay and transwell cell rnigration assay. Expression levels of MMP1, MMP2, TIMP1, and TIMP2 were measured by quantitative real-time polymerase chain reaction (RT-PCR). Results: Migration of PRDM 14-shRNA-infected cells was significantly inhibited relative to control cells as measured by the scratch wound healing (P 〈 0.05) and transwell cell migration assays (P 〈 0.01 ). The expression of MMPI in A549 cells infected by PRDMI4-shRNA was down-regulated significantly (P 〈 0.01 ), whereas the expression ofTIMP 1 and TIMP2 was up-regulated significantly (P 〈 0.01 ). Conclusions: PRDM 14 accelerates A549 cells migration in vitro through extracellular matrix degradation. PRDM 14 is considered as a potential therapeutic target in metastatic NSCLC.展开更多
文摘Objective:To assess prognostic factors and validate the effectiveness of recursive partitioning analysis (RPA) classes and graded prognostic assessment (GPA) in 290 non-small cell lung cancer (NSCLC) patients with brain metastasis (BM).Methods:From Jan 2008 to Dec 2009,the clinical data of 290 NSCLC cases with BM treated with multiple modalities including brain irradiation,systemic chemotherapy and tyrosine kinase inhibitors (TKIs) in two institutes were analyzed.Survival was estimated by Kaplan-Meier method.The differences of survival rates in subgroups were assayed using log-rank test.Multivariate Cox's regression method was used to analyze the impact of prognostic factors on survival.Two prognostic indexes models (RPA and GPA) were validated respectively.Results:All patients were followed up for 1-44 months,the median survival time after brain irradiation and its corresponding 95% confidence interval (95% CI) was 14 (12.3-15.8) months.1-,2-and 3-year survival rates in the whole group were 56.0%,28.3%,and 12.0%,respectively.The survival curves of subgroups,stratified by both RPA and GPA,were significantly different (P0.001).In the multivariate analysis as RPA and GPA entered Cox's regression model,Karnofsky performance status (KPS) ≥ 70,adenocarcinoma subtype,longer administration of TKIs remained their prognostic significance,RPA classes and GPA also appeared in the prognostic model.Conclusion:KPS ≥70,adenocarcinoma subtype,longer treatment of molecular targeted drug,and RPA classes and GPA are the independent prognostic factors affecting the survival rates of NSCLC patients with BM.
基金supported by a National Research Foundation of Korea (NRF)grant funded by the Korean government (MEST) (No. 2012‐0000475)
文摘Although non-small cell lung cancer (NSCLC) can metastasize to almost any organ, metastasis to the gallbladder with significant clinical manifestation is relatively rare. Here, we report a case of gallbladder metastasis of NSCLC presenting as acute cholecystitis. A 79-year-old man presented with pain in the right upper quadrant and fever. A computed tomography (CT) scan of the chest and abdomen showed a cavitary mass in the right lower lobe of the lung and irregular wall thickening of the gallbladder. Open cholecystectomy and needle biopsy of the lung mass were performed. Histological examination of the gallbladder revealed a moderately-differentiated squamous cell carcinoma displaying the same morphology as the lung mass assessed by needle biopsy. Subsequent immunohistochemical examination of the gallbladder and lung tissue showed that the tumor cells were positive for P63 but negative for cytokeratin 7, cytokeratin 20 and thyroid transcription factor-1. A second primary tumor of the gallbladder was excluded by immunohistochemical methods, and the final pathological diagnosis was gallbladder metastasis of NSCLC. Although the incidence is extremely rare, acute cholecystitis can occur in association with lung cancer metastasis to the gallbladder.
基金Supported by a grant from the National Natural Science Foundation of China(No.81502521).
文摘Objective The brain is the main site of failure in cancer patients with epidermal growth factor receptor(EGFR)mutations undergoing treatment.However,identifying patients who may develop brain metastases(BM)is difficult.Autophagy is critical for cancer initiation and progression.We hypothesized that genetic variants in autophagy core genes might contribute to BM risk of non-small cell lung cancer(NSCLC)following treatment with EGFR tyrosine kinase inhibitor(EGFR-TKIs).Methods We systematically examined 16 potentially functional genetic polymorphisms in seven autophagy core genes among 105 TKI-treated NSCLC patients.Kaplan-Meier curves were plotted to assess the cumulative BM probability.Univariate and multivariate Cox proportional hazard regression analyses were utilized to calculate hazard ratios(HRs)and 95%confidence intervals(CIs).We evaluated the potential associations of these genes with subsequent BM development.Results We found that ATG16L1:rs2241880,ATG10:rs10036653,rs3734114,and ATG3:rs7652377 are significantly associated with NSCLC treated with EGFR-TKIs(all P<0.05).BM developed more often in patients with ATG3 rs7652377 CC genotype(33%),ATG10 rs10036653 AA genotype(43%),ATG10:rs3734114 CT/CC genotype(46%),and ATG16L1 rs2241880 AA genotype(37%)compared to patients with AA genotypes at rs7652377(12%),AT/TT genotypes at rs10036653(16%),the TT genotype at rs3734114(13%),or AG/GG genotypes at rs2241880(17%).Conclusion These associations may be critical for understanding the role of autophagy in BM risk.Future prospective studies are needed to determine if prophylactic cranial irradiation(PCI)could offer a survival benefit in this group of patients.
文摘Objective: The aim of this study is to compare the effectiveness of surgery with stereotactic radiosurgery (SRS) for patients with a single synchronous brain metastasis from successfully treated non-small cell lung cancer. Methods: Between 1995 and 2002, 53 patients underwent resection of both primary non-small cell lung cancer and the associated single brain metastasis. There were 33 men and 20 women with a mean age of 57 years (range, 32-85 years). At the time of diagnosis, 42 patients experienced lung cancer related symptoms, whereas 11 patients experienced brain metastases-related symptoms. 42 patients had received thoracic surgery first, and 11 patients had undergone neurosurgery or radiosurgery first. Pneumonectomy was performed in 9 out of 42 patients (21.4%), lobectomies in 30 (71.4%), and wedge resection in 3 (7.2%). 48 patients (90.5%) underwent complete lymphadenectomy. 35 patients underwent brain metastasectomy. 18 underwent SRS. Results: There was no postoperative mortality and severe complications after either lung or brain surgery. Histology showed 34 adenocarcinomas, 16 squamous cell carcinomas, and 3 large cell lung cancers. 15 patients (28.3%) had no evidence of lymph node metastases (No), 20 patients (37.7%) had hilar metastases (N1), and 18 patients (34%) had mediastinal metastases (N2). The 1-, 2-, 3- and 5-year overall survival rates were 49%, 19%, 10%, and 5%, respectively. The corresponding data for neurosurgery group were 55%, 17%, 11%, and 6%, respectively. The median survival time was 13 months. For SRS group the corresponding data were 44.8%, 20.9% 10.5%, and 2%, respectively. The median survival time was 14 months. The differences between the two groups were not significant (P〉0.05). In lymph node negative patients (No), the overall 5-year survival rate was 10%, as compared with a 1% survival rate in patients with lymph node metastases (N1-2). The difference was significant (P〈0,01). For adenocarcinomas, the 5-year survival rate was 5%. The correspondent data for squamous cell lung cancers was 3%. The difference was not significant (P〉0.05). Conclusion: Although the overall survival rate for patients who have brain metastases from NSCLC is poor, surgical resection or radiosurgery may be beneficial in a select group of patients with synchronous brain metastases and lung cancer without lymph node metastases.
文摘BACKGROUND The presence of liver metastasis(LM) is an independent prognostic factor for shorter survival in non-small cell lung cancer(NSCLC) patients.The median overall survival of patients with involvement of the liver is less than 5 mo.At present,identifying prognostic factors and constructing survival prediction nomogram for NSCLC patients with LM(NSCLC-LM) are highly desirable.AIM To build a forecasting model to predict the survival time of NSCLC-LM patients.METHODS Data on NSCLC-LM patients were collected from the Surveillance,Epidemiology,and End Results database between 2010 and 2018.Joinpoint analysis was used to estimate the incidence trend of NSCLC-LM.Kaplan-Meier curves were constructed to assess survival time.Cox regression was applied to select the independent prognostic predictors of cancer-specific survival(CSS).A nomogram was established and its prognostic performance was evaluated.RESULTS The age-adjusted incidence of NSCLC-LM increased from 22.7 per 1000000 in 2010to 25.2 in 2013,and then declined to 22.1 in 2018.According to the multivariable Cox regression analysis of the training set,age,marital status,sex,race,histological type,T stage,metastatic pattern,and whether the patient received chemotherapy or not were identified as independent prognostic factors for CSS(P < 0.05) and were further used to construct a nomogram.The C-indices of the training and validation sets were 0.726 and 0.722,respectively.The results of decision curve analyses(DCAs) and calibration curves showed that the nomogram was well-discriminated and had great clinical utility.CONCLUSION We designed a nomogram model and further constructed a novel risk classification system based on easily accessible clinical factors which demonstrated excellent performance to predict the individual CSS of NSCLC-LM patients.
文摘Objective:To investigate the relationship between postoperative metastasis and circulating levels of osteopontin in non-small cell lung cancer(NSCLC).Methods:The expression of osteopontin mRNA were detected with RT-PCR technique.The circulating levels of osteopontin were measured through ELASA in 46 NSCLC cases that had not been received any anti-cancer treatment at the time of sampling.The tissues from fifteen patients with benign pulmonary diseases were studied as control group.Results:The overall median mRNA expression level of osteopontin was approximately 70-fold higher in tumor tissues than in matched normal lung tissues(P0.001).Over-expression of osteopontin mRNA was significantly associated with clinical stage(P=0.009).Advanced disease states had higher circulating level of osteopontin(stage I+II versus stage III+VI).In multivariate analysis,stage was the only independent factor influencing circulating levels of osteopontin.All patients were followed up for 12 months,2 of the 46 patients with both osteopontin mRNA expression and elevated plasma osteopontin levels had local recurrence and 10 had distant metastasis.There was a significant difference in the osteopontin levels between metastasis group and non-metastasis group.Conclusion:Preoperative plasma levels of osteopontin are significantly associated with post-operative metastasis in advanced NSCLC.
文摘INTRODUCTION Non-small cell lung cancer(NSCLC)is a common malignant disease with an extremely poor prognosis.Lung cancer has been reported to metastasize to the eye in 0.2%to7%of patients based on clinical studies,and in 6%to 7%of patients based on postmortem histopathologic studies.
文摘Objective The aim of this study was to explore the mechanism behind lncRNA small nucleolar RNA host gene 19(lncRNA SNHG19)/microrNA-299-5P(miR-299-5p)/mitogen-activated protein kinase 6(MAPK6)signaling axis promoting metastasis of non-small cell lung cancer(NSCLC).Methods To analyze the abnormal expression of lncRNAs in NSCLC,50 surgically resected NSCLC and adjacent tissue samples were collected from August 2021 to August 2022.The mRNA expression levels of lncRNA SNHG19,Mir-299-5p,and MAPK6 were detected by qRT-PCR.The functions of lncRNA SNHG19,Mir-299-5p and MAPK6 were investigated by CCK-8,clone formation,EdU,scratch,Transwell western blotting(WB)and in vivo xenograft assay.RNA fluorescence in-situ hybridization(FISH),RNA pull-down,dual luciferase reporter,and RNA co-immunoprecipitation assays were used to explore the mechanism of action between lncRNA SNHG19,miR-299-5p,and MAPK6.Results High expression of lncRNA SNHG19 was correlated with poor prognosis,tumor size,lymph node metastasis,and TNM stage in NSCLC patients(P<0.05).Cell function experiments showed that lncRNA SNHG19 could improve the proliferation,clone formation,migration,and invasion ability of A549 cells both in vitro and in vivo(all P<0.05)and increased the relative expression levels of vimentin and MAPK6(P<0.05).The relative expression level of E-cadherin was decreased(P<0.05).lncRNA SNHG19 can interact with Mir-299-5p and regulate the expression level of MAPK6.Conclusion lncRNA SNHG19 is upregulated in NSCLC tissues and cells,and its high expression is associated with tumor progression and poor survival.Moreover,it can act as a molecular sponge for Mir-299-5p to regulate MAPK6 expression and promote the proliferation and metastasis of A549 cells.
文摘Objective To study the risk factors of mediastinal lymph node metastasis in patients with ≤3 cm peripheral non small cell lung cancer. Methods From January 2000 to December 2010,a total of 281 patients with NSCLC [152 men and 129 women,aged (60. 31 ± 12. 13) years; ≤ 3 cm in diameter]underwent lobectomy or partial resection with systematic mediastinal lymphadenectomy in hospital. Clinical data included age,gender,
文摘To study the effect of IL-18 and nitric oxide(NO) on the growth and metastasis of non-small cell lung cancer (NSCLC).Methods Serum IL-18 and nitrate and nitrite levels in 82 patients with NSCLC and 20 healthy control subjects were measured by using ELISA and Griess.Results The levels of serum IL-18 were (334.2±31.0)ng/L in NSCLC patients and (151.3±22.0)ng/L in control subjects,respectively.The levels of nitrate and nitrite were (237.1±21.0)μmol/L in NSCLC patients and (44.2±15.0)μmol/L in control subjects.The levels of serum IL-18 and nitrate and nitrite were not related with age,gender,histological types in patients with NSCLC.The levels of serum IL-18 was closely associated with TNM stage,lymph node metastasis and distal metastasis,but not with its degree and organ types of metastasis.There was a negative correlation between the levels of serum IL-18 and nitrate and nitrite.Conclusion Serum IL-18 and nitrate and nitrite levels may be useful to evaluate the prognosis of the patients with NSCLC.16 refs,2 tabs.
文摘Postoperative recurrence occurs in approximately half of patients with non-small cell lung cancer(NSCLC), even after complete resection. Disease recurrence after surgical resection reduces the patient's life expectancy sharply. The prognosis after postoperative recurrence is considered to largely depend on both the mode of first recurrence(distant, locoregional or combined) and the treatment modality:(1) The majority of cases of postoperative recurrence involve distant metastasis with or without locoregional recurrence. Platinum-based systemic chemotherapy is practically accepted as the treatment for these diseases on the basis of evidence for original stage Ⅳ disease. The advent of both pemetrexed and molecular-targeted drugs has improved the survival of nonsquamous NSCLC and changed the chemotherapeutic algorithm for NSCLC;(2) Among patients with distant metastatic recurrence without locoregional recurrence at the primary tumor site, the metastasis is often limited in both organ and number. Such metastases are referred to as oligometastases. Local therapy, such as surgical resection and radiotherapy, has been suggested to be the first-line treatment of choice foroligometastatic recurrence; and(3) While locoregional recurrence is likely to cause troublesome symptoms, it is a potentially limited disease. Therefore, providing local control is important, and radiation is usually beneficial for treating local recurrence. In order to obtain better control of the disease and provide treatment with curative intent in patients with limited disease, the administration of concurrent platinum-based chemoradiotherapy is recommended according to the results of originally nonresectable stage ⅢA and ⅢB disease.
基金Supported by Grants from the National Science Council,Taiwan,ROCin part by the Ministry of Education,Taiwan,ROC under the ATU plan
文摘Lung cancer is the leading cause of cancer-related mortality throughout the world. Non-small cell lung cancer(NSCLC) accounts for 85% of all diagnosed lung cancers. Despite considerable progress in the diagnosis and treatment of the disease, the overall 5-year survival rate of NSCLC patients remains lower than 15%. The most common causes of death in lung cancer patients are treatment failure and metastasis. Therefore, developing novel strategies that target both tumour growth and metastasis is an important and urgent mission for the next generation of anticancer therapy research. Heat shock proteins(HSPs), which are involved in the fundamental defence mechanism for maintaining cellular viability, are markedly activated during environmen-tal or pathogenic stress. HSPs facilitate rapid cell division, metastasis, and the evasion of apoptosis in cancer development. These proteins are essential players in the development of cancer and are prime therapeutic targets. In this review, we focus on the current understanding of the molecular mechanisms responsible for HLJ1's role in lung cancer carcinogenesis and progression. HLJ1, a member of the human HSP 40 family, has been characterised as a tumour suppressor. Research studies have also reported that HLJ1 shows promising dual anticancer effects, inhibiting both tumour growth and metastasis in NSCLC. The accumulated evidence suggests that HLJ1 is a potential biomarker and treatment target for NSCLC.
文摘Objective: To investigate the expression characteristics of Livin and second mitochondrial activator of Caspase (Smac) proteins in non-small cell lung cancer (NSCLC), and analyze their effect on patients' prognosis. Methods: The expressions of Livin and Smac proteins were detected in 89 NSCLC tissue samples and 25 normal lung tissue samples by immunohistochemical technique. Results: The positive expression rates of Livin and Smac proteins in NSCLC tissues were 53.9%, and 58.4% respectively, higher than that in normal lung tissues(P〈0.01). Livin protein expression correlated with Smac protein significantly(Χ^2=1 8.451, P=0.000, r=0.455). The expression level of Livin protein was closely related to lymph node metastasis, TNM stage and histological type (P〈0.05), but not to sex, age, differentiation grade (P〉0.05). The expression level of Smac protein was closely related to lymph node metastasis, TNM stage (P〈0.01), but not to sex, age, histological types (P〉0.05). Kaplan-Meier analysis revealed a significant impact on survival by Livin protein in NSCLC (P〈0.01), but not by Smac protein (P〉0.05). Conclusion: Overexpression of Livin protein may play a promoting role in the occurrence and progression of NSCLC. Moreover, it may bring an adverse effect on patients' prognosis. Although overexpression of Smac protein affects the occurrence and progression of NSCLC, it has no relationship with the prognosis. Livin protein may be helpful to evaluate the progression of NSCLC, and to predict the prognosis.
基金supported by the National Natural Science Foundation of China(Nos.82202989 and 82003089)the Regional Innovation Cooperation Project of the Sichuan Science and Technology Program(No.2021YFQ0029)+4 种基金the China Postdoctoral Science Foundation(No.2022M722279)the Sichuan Science and Technology Program(No.2023YFS0163)the Postdoctoral Research Project of West China Hospital,Sichuan University,Chengdu,China(No.2021HXBH045)Fundamental Research Funds for the Central Universities(No.2022SCU12063)the Sichuan University Postdoctoral Interdisciplinary Innovation Fund(awarded to Lingling Zhu).
文摘Liver metastases(LMs)are common in lung cancer.Despite substantial advances in diagnosis and treatment,the survival rate of patients with LM remains low as the immune-suppressive microenvironment of the liver allows tumor cells to evade the immune system.The impact of LMs on the outcomes of immune checkpoint inhibitors in patients with solid tumors has been the main focus of recent translational and clinical research.Growing evidence indicates that the hepatic microenvironment delivers paracrine and autocrine signals from non-parenchymal and parenchymal cells.Overall,these microenvironments create pre-and post-metastatic conditions for the progression of LMs.Herein,we reviewed the epidemiology,physiology,pathology and immunology,of LMs associated with non-small cell lung cancer and the role and potential targets of the liver microenvironment in LM in each phase of metastasis.Additionally,we reviewed the current treatment strategies and challenges that should be overcome in preclinical and clinical investigations.These approaches target liver elements as the basis for future clinical trials,including combinatorial interventions reported to resolve hepatic immune suppression,such as immunotherapy plus chemotherapy,immunotherapy plus radiotherapy,immunotherapy plus anti-angiogenesis therapy,and surgical resection.
文摘Lung cancer metastasis is typically determined by histologic similarity between distant and primary lesions. Herein, we present a 70-year-old Japanese woman with an adenocarcinoma in her lung and a squamous cell carcinoma in her femur; both tumors had an identical epidermal growth factor receptor mutation, G719 S. This indicated that both tumors had a common origin, despite their histologic dissimilarity. The tumor in the femur was thus identified genetically as a lung cancer metastasis. This case suggests that genetic analysis can determine whether a distant lesion is a lung cancermetastasis, particularly when the histology differs from that of the primary lesion.
基金support from the National Natural Science Foundation of China(Nos.82003206 and 82173338)Natural Science Foundation of Hunan Province(Nos.2020SK2031,2020SK2030,2021RC4040,and 2020JJ3025).
文摘Background:Immune checkpoint inhibitors(ICIs)are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer(NSCLC)harboring no actionable mutations;however,data on their efficacy among patients presenting with intracranial lesions are limited.This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis.Methods:Our study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable,asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1,2019 and September 30,2021.The patients were stratified into two groups according to the first-line treatment regimen received:ICI combined with chemotherapy(n=102)or chemotherapy(n=109).Systemic and intracranial objective response rates(ORRs)and progression-free survival(PFS)were analyzed.Adverse events were also compared between the groups.Results:Compared with the chemotherapy-based regimen,the ICI-containing regimen was associated with a significantly higher intracranial(44.1%[45/102]vs.28.4%[31/109],χ^(2)=5.620,P=0.013)and systemic(49.0%[50/102]vs.33.9%[37/109],χ^(2)=4.942,P=0.019)ORRs and longer intracranial(11.0 months vs.7.0 months,P<0.001)and systemic(9.0 months vs.5.0 months,P<0.001)PFS.Multivariable analysis consistently revealed an independent association between receiving ICI plus platinum-based chemotherapy as a first-line regimen and prolonged intracranial PFS(hazard ratio[HR]=0.52,95%confidence interval[CI]:0.37-0.73,P<0.001)and systemic PFS(HR=0.48,95%CI:0.35-0.66,P<0.001).No unexpected serious adverse effects were observed.Conclusion:Our study provides real-world clinical evidence that ICI combined with chemotherapy is a promising first-line treatment option for driver gene mutation-negative advanced NSCLC patients who present with brain metastasis at initial diagnosis.Clinical trial registration:https://www.clinicaltrials.gov/,OMESIA,NCT05129202.
文摘Background: As a novel molecular markerof non-small cell lung cancer (NSCLC), PRDI-BFI and R1Z homology domain containing protein 14 (PRDM 14) is over-expressed ill NSCLC tumor tissues. Extracellular matrix degradation mediated by the balance between matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) is one of the most important mechanism in king cancer metastasis. This study aimed to determine if PRDM14 promoted the migration of NSCLC cells through extracellular matrix degradation mediated by change of MMP/TIMP expression. Methods: The expression of PRDM 14 was down-regulated in human cell line A 549 after transfection with lentiviral vector-mediated short-hairpin ribonucleic acids (shRNAs) which targeted the PRDM 14 promoter. Cellular migration ofshRNA-infected cells was detected by a scratch wound healing assay and transwell cell rnigration assay. Expression levels of MMP1, MMP2, TIMP1, and TIMP2 were measured by quantitative real-time polymerase chain reaction (RT-PCR). Results: Migration of PRDM 14-shRNA-infected cells was significantly inhibited relative to control cells as measured by the scratch wound healing (P 〈 0.05) and transwell cell migration assays (P 〈 0.01 ). The expression of MMPI in A549 cells infected by PRDMI4-shRNA was down-regulated significantly (P 〈 0.01 ), whereas the expression ofTIMP 1 and TIMP2 was up-regulated significantly (P 〈 0.01 ). Conclusions: PRDM 14 accelerates A549 cells migration in vitro through extracellular matrix degradation. PRDM 14 is considered as a potential therapeutic target in metastatic NSCLC.