Clinical Characteristic And The Mechanism Of Patients With Brain Metastases As First Symptom Of Lung Cancer

ObjectiveThe morbidity of lung cancer appears to be rising by years. Lung cancer is the leading cause of cancer death. There is a distinct kind of lung cancer which start with the first symptom of neurological symptom. The clinical characteristic of it is the symptom of lung be concealed, develop quickly, high-fatalite rate and poor prognosis. Therefore the first part of article study the clinic characteristic of patients who start with the first symptom of neurological symptom, and then analysis the prognosis factors so that retrospective study could provides the help with early diagnosis, better treatment and evaluate the prognosis of this kind of lung cancer patients.The FRAS1is a potential regulator of cell proliferation, and migration in the brain metastasis of lung cancer. In the early study, we have confirmed that FRAS1is high expressed in the lung cancer patients with brain metastasis. Therefore the second part of study is to observe effects of FRAS1on proliferation, migration by the brain metastases, to reveal the the mechanism of brain metastases.MethodsThe first part:Between January2003and December2011, patients with brain meastasis who were treated at Huashan hospital Fudan University Shanghai China were reviewed.252cases met the study criteria:(1) brain metastases presented with neurological symptoms as first symptom of cancer;(2) there was not a history of previous malignancies;(3) there was not a clinical evidence of current malignant tumor;(4) patients had no other sites of active metastases;(5) diagnosis of brain lesions must be confirmed histotogically as lung cancer. Variables such as symptoms, imaging studies, extracerebral metastases, primary sites, initial diagnosis and survival data were obtained and retrospectively analyzed.Kaplan and Meier method was used to do the survival analysis in the whole cohort and the subgroup of patients with lung cancer, respectively. The differences betweenthe Kaplan-Meier curves were determined with the Log-rank test (univariate analysis). The prognostic factors that were borderline significant were included in a multivariate analysis and performed with the Cox proportional hazards model. All statistical analyses were performed under SPSS15.0computer package.The second part:A549, SK-mes1, and Calul lung cancinoma cells were transfected with FRAS1. MTS assay was carried out to determine the role of FRAS1in the proliferation of3kinds of lung cancinoma cells:A549, SK-mesl, and Calu1. The effects on migration of FRAS1were inspected by using Boyden Chamber TranswelI method.Results1. Follow-up was obtained in252cases (85.9%).40.1%of patients were wrong diagnosed as other benign diseases. Glioma was the most one.2. Symptoms of intracranial hypertension were common first symptoms, which occupy about2/3of total group. The majority of cases were adenocarcinomas, which occupy about58%of total group. Majority of the lesions often located in the cerebrum (70%) as single lesion(63.9%).The extracerebral metastases were appeared in the bone and lung, which takes38%and24%.3. The median survival time was16months (0.5-67months) of252patients with brain metastases as first symptom of lung cancer. The median survival time of patients was14months (95%confidence interval,12.49-15.51months), and the actuarial survival rate for1,2and5years was54.6%,31.3%and9.0%, respectively.4. On univariate analysis, improved overall survival was associated with if age over60, an indolent or sharp clinical course, adenocarcinoma or not, well or poor differentiated carcinomas,treat lung lesion with radiotherapy or not, treat with EGFR-TKI or not.5. On multivariate analysis, factors significantly affecting the survival included those as follows:if age over60, an indolent or oneset clinical course, adenocarcinoma or not, treat with EGFR-TKI or not.6. FRAS1shRNA could not inhibited the proliferation of lung cells. In the migration experiment, the average of trans-membrane cell number in FRAS1shB178transfected Calul lung cancinoma cells was215.6/HT, and the blank plasmid transfected Calul lung cancinoma cells was was595.8/HT.(P<0.05).There was signitlcant difference between the groups.Conclusions1. The majority of patients with neurological symptom as first symptom of lung cancer were adenocarcinomas. Intracranial hypertension were common first symptoms. Majority of the lesions often located in the cerebrum. 2. The overall prognosis is poor for patients with neurological symptom as first symptom of lung cancer, the actuarial survival rate for5years was under10%.3. On multivariate analyses, factors significantly affecting the survival of patients with brain metastases as first symptom of lung cancer included those as follows:if age over60, an indolent or onset clinical course, adenocarcinoma or not, treat with EGFR-TKI or not.4. FRAS1may be one of its mechanisms in inhibiting the invasion brain metastases of lung cancer.