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Study shows way to predict lung cancer recurrence
WASHINGTON (Reuters) - It may be possible to predict whose lung cancer is likely to come back after surgery has apparently cured it, U.S. researchers reported on Wednesday.
And the findings could lead to more effective treatments for lung cancer, a theory they are testing, the researchers reported in the New England Journal of Medicine.
They saw clear changes in four genes in patients whose cancer came back within five years after surgery and said the findings might be used as the basis for a test.
Patients found to have a high risk might consider special chemotherapy after surgery.
\"These people are at increased risk of recurrence. We think that there are numerous ways that you can take care of them,\" said Dr. Malcolm Brock of Johns Hopkins University in Baltimore, who led the study.
\"One is of course more chemotherapy. But we also believe that by giving them targeted therapies, new types of therapies, we can help these patients,\" Brock said in a telephone interview.
Brock's team tested 157 patients with stage I non small cell lung cancer who had had small tumors surgically removed.
Of the patients, 51 had the cancer come back within 40 months -- just over three years -- while 116 stayed tumor-free.
\"The four genes of interest in our study are p16, CDH13, APC, and RASSF1A. They are involved in cell-cycle control (p16), invasion and metastasis (CDH13, APC), and Ras signaling (RASSF1A),\" the researchers wrote.
The researchers' test has been licensed to Belgian biotech company OncoMethylome.
'DNA FORENSICS'
\"This is DNA forensics for cancer,\" Brock said.
\"All of these tumors that we are talking about are early stage tumors. They are very small,\" he added. Yet a third of patients with such tumors have their cancer return.
After surgery, it appears all the cancer is gone. Pathologists look at the nearby tissue and lymph nodes under a microscope and declare the patient cancer-free.
\"But in 40 months the patient comes back with metastatic disease in all of their body. How is that possible?\" Brock asked. \"It must be that the microscope, which is a 17th century innovation ... is not picking up all of the disease.\"
But the DNA test does, Brock believes. And the findings could lead to new treatments for lung cancer, one of the deadliest cancers.
Some drugs can home in on these changes however -- notably drugs used to treat myelodysplastic syndromes, sometimes known as pre-leukemia. They are known as hypomethylating agents and include 5-azacytidine, decitabine and lenalidomide.
Brock's team is also testing these agents in lung cancer patients. \"There are lots of them and there are lots of choices,\" he said.
He believes the test has wider uses. \"We really think that if this can be validated that it would have broader applications to other solid tumors,\" he said.
\"It gives weight to an idea that your tumor DNA and my tumor DNA might be slightly different. It might even show us ways that we can do personalized therapy.\"
Lung cancer kills more than 1 million people each year worldwide. Only 15 percent of patients survive five years or more.
http://www.reuters.com/article/healthNews/idUSN1225803620080313
再贴个原文
DNA Methylation Markers and Early Recurrence in Stage I Lung Cancer
ABSTRACT
Background
Despite optimal and early surgical treatment of non–small-cell lung cancer (NSCLC), many patients die of recurrent NSCLC. We investigated the association between gene methylation and recurrence of the tumor.
Methods
Fifty-one patients with stage I NSCLC who underwent curative resection but who had a recurrence within 40 months after resection (case patients) were matched on the basis of age, NSCLC stage, sex, and date of surgery to 116 patients with stage I NSCLC who underwent curative resection but who did not have a recurrence within 40 months after resection (controls). We investigated whether the methylation of seven genes in tumor and lymph nodes was associated with tumor recurrence.
Results
In a multivariate model, promoter methylation of the cyclin-dependent kinase inhibitor 2A gene p16, the H-cadherin gene CDH13, the Ras association domain family 1 gene RASSF1A, and the adenomatous polyposis coli gene APC in tumors and in histologically tumor-negative lymph nodes was associated with tumor recurrence, independently of NSCLC stage, age, sex, race, smoking history, and histologic characteristics of the tumor. Methylation of the promoter regions of p16 and CDH13 in both tumor and mediastinal lymph nodes was associated with an odds ratio of recurrent cancer of 15.50 in the original cohort and an odds ratio of 25.25 when the original cohort was combined with an independent validation cohort of 20 patients with stage I NSCLC.
Conclusions
Methylation of the promoter region of the four genes in patients with stage I NSCLC treated with curative intent by means of surgery is associated with early recurrence.
http://content.nejm.org/cgi/content/short/358/11/1118
DNA甲基化标志物与 I 期肺癌的早期复发相关
背景：尽管NSCLC最适合早期手术治疗，但是很多病人死于NSCLC复发。我们研究基因甲基化和肿瘤复发的联系。
方法：基于年龄，NSCLC分期，性别，手术时间配对，将116例I 期NSCLC曾接受过根治性切除术， 40内没复发的患者作为对照， 与51例I 期NSCLC曾接受过根治性切除术，切除术后40月内复发患者进行比较。我们研究肿瘤和淋巴结中7个基因的甲基化是否与肿瘤复发相联系。
结果：回归分析发现，肿瘤和肿瘤阴性淋巴结中的细胞周期蛋白依赖性激酶抑制剂2A基因p16，H-钙粘蛋白基因CDH13，Ras相关区域家族1基因RASSF1A，结肠腺瘤息肉病基因APC的启动子甲基化与肿瘤复发相关，不依赖于NSCLC分期，年龄，性别，种族，吸烟史，肿瘤的组织学特点。肿瘤和纵隔淋巴结中的p16和CDH13的启动子甲基化与肿瘤复发相关，原始队列比值比为15.50；当原始队列与独立认证20例I期NSCLC患者相结合进行比较，比值比为25.25.
结论：接受过根治性手术的I期NSCLC患者的4个基因启动子的甲基化与早期复发相关。 |
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发表于 2008-4-2 06:41:09