驗血可有效地及早偵測GI癌症


  【24drs.com】January 21, 2010 (佛州奧蘭多) — 研究者在2010年胃腸道癌症研討會中報告指出兩種驗血方法,分別可以及早偵測大腸直腸癌和胰臟癌。
  
  這個年會由美國胃腸道協會、美國臨床腫瘤協會、美國放射腫瘤協會、腫瘤外科協會共同贊助。
  
  來自以色列的一個團隊報告指出,一種簡單的CD24蛋白質驗血方法,對於偵測大腸直腸癌可以有超過90%的敏感度與專一性,且在辨識腺瘤的準確度超過80%。
  
  CD24蛋白質是一種細胞表面蛋白質以及P-選擇素配位體(P-selectin ligand),與細胞黏附和轉移有關,曾有研究指出和大腸直腸癌(colorectal cancer,CRC)有關(Gastroenterology. 2006;131:630-639),目前這個研究的目標是,評估CD24蛋白質在正常者和CRC或腺瘤患者之週邊血液淋巴球(peripheral blood lymphocytes,PBLs)中的表現。
  
  以色列特拉維夫Souraski醫學中心研究實驗室主任Sarah Kraus博士在發表時表示,目前沒有具足夠敏感度或專一性的驗血方式。
  
  她在簡報中表示,我們發現,多數CRC或腺瘤病患的血清CD24值升高,我們相信,檢測週邊血液淋巴球中CD24值的簡單驗血方式,可以成功地分辨出那些有腫瘤的人,或許也可以作為及早偵測和監測CRC的生物標記。
  
  該研究中,150名對象接受大腸鏡檢查,從血清樣本分離週邊血液淋巴球,分析這些研究對象的蛋白質粹取物,在第2次的確認試驗中對73名研究對象進行同樣的步驟,在此發表的就是這些結果。
  
  Kraus博士指出,CD24蛋白質被證實可以在大腸鏡檢查無異常者中,有敏感性和專一性地分辨CRC和腺瘤病患。正常者的此一蛋白質數值約 2000 OD/mm2 ,腺瘤或癌症患者則為12,000 OD/mm2。
  
  偵測CRC的敏感性是92.3%、腺瘤是75.0%,專一性則分別是83.8%和89.2%,合併兩組進行分析,敏感度是78.4%、專一性是86.8%。
  
  【也可及早偵測出胰臟癌】
  另一篇研究中,一種免疫分析方法顯示可有效偵測早期胰臟癌且有高準確度,此分析分辨和量化血清PAM4蛋白質,一種在將近90%的胰臟癌都出現的抗原,但是在良性病灶或其他腫瘤不常發現。
  
  紐澤西州貝里維爾花園州癌症研究中心的David V. Gold博士表示,我們發現,PAM4蛋白質在分辨胰臟癌病患相當準確,如果以更大型的研究確認,將是一個可以有效偵測此疾病的工具,加上可能治癒的手術,將是獲得好結果的更佳機會。此研究與馬里蘭州巴爾的摩的約翰霍普金斯醫學研究中心合作。
  
  PAM4單株抗體,也稱為clivatuzumab,以相當高的敏感度辨識一種獨特的生物標記:胰臟腺癌分泌的粘液醣蛋白,正常人或慢性胰臟炎病患的胰臟細胞不會偵測到這種蛋白質,慢性胰臟炎是一種很難和癌症分辨的狀況。
  
  Gold博士向媒體代表們表示,PAM4檢測可以偵測出血液中的PAM4抗原,一種由腫瘤分泌的蛋白質,這可以作為診斷和標靶治療的標記。Gold博士報告指出,對68個進行胰臟手術的病患以及19個健康對照組進行PAM4酵素免疫分析,偵測胰臟癌的整體敏感度是81%;偵測第1期胰臟癌的敏感度是62%,偵測第2期疾病的敏感度是86%,偵測第3/4期疾病的敏感度是91%。
  
  他表示,PAM4分析偵測出絕大多數早期胰臟癌的病患以及91%的晚期疾病,PAM4對胰臟癌有相當的專一性,它代表病患相當可能有胰臟癌。
  
  Gold博士預測,這項檢測不會被用於廣泛篩檢,但是最好可以用於懷疑有癌症的病患,或者胰臟癌高風險者,包括長期慢性胰臟炎和糖尿病、重度菸癮和飲酒者,以及家族遺傳性胰臟炎或胰臟癌病史者。
  
  兩位研究者都指出,他們的分析正在進一步研發,或許可以在2-3年臨床運用。
  
  主持該簡報的北達科他州醫學健康科學學院外科教授Robert Sticca醫師解釋,這些研究是發展可以更準確地早期偵測胃腸道癌症之諸多努力的一部份。
  
  他表示,對於胰臟癌,醫界在治療上一直有所困難,這些是令人振奮的資料,如果我們可以及早偵測它,我們將可以有更多處置方法以及防止死亡。
  
  大腸直腸癌部份也是初步資料,但是如果這個檢測方式獲得證實,對於預防死於此一常見的癌症將大有幫助。
  
  研究者皆宣告沒有相關財務關係。
  
  2010年胃腸道癌症研討會:摘要OP162與135。發表於2010年1月22-24日。

Blood Tests Promising for Early Detection of GI Cancers

By Caroline Helwick
Medscape Medical News

January 21, 2010 (Orlando, Florida) — Investigators reported promising results from 2 blood tests that could allow for the early detection of colorectal and pancreatic cancers here at the 2010 Gastrointestinal Cancers Symposium.

The annual meeting is cosponsored by the American Gastroenterological Association, the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

A team from Israel reported that a simple test for blood levels of the CD24 protein is more than 90% sensitive and specific for detecting colorectal cancer, and more than 80% accurate at identifying adenomas.

The CD24 protein is a cell-surface protein and P-selectin ligand that is involved in cell adhesion and metastasis, and has previously been associated with colorectal cancer (CRC) (Gastroenterology. 2006;131:630-639). The aim of the current study was to evaluate CD24 protein expression in peripheral blood lymphocytes (PBLs) from normal subjects and from subjects with CRC or adenomas.

"There is currently no serum-based test that is of sufficient sensitivity or specificity to be useful," said Sarah Kraus, PhD, who presented the findings. Dr. Kraus heads the research laboratory at Tel Aviv Souraski Medical Center in Israel.

"We found that serum CD24 is elevated in the majority of patients with CRC or adenomas. We believe a simple blood test that measures the level of CD24 in PBLs can successfully distinguish healthy subjects from those with neoplasia, and may serve as a biomarker for early detection and surveillance of CRC," she said at a press briefing.

In the study, 150 consecutive subjects underwent colonoscopy. PBLs were isolated from serum samples, and protein extracts were analyzed for these subjects. The same procedure was followed in a second validation trial of 73 consecutive subjects, for whom results were presented here.

CD24 protein levels proved to be sensitive and specific for distinguishing patients with no abnormal findings on colonoscopy from those with CRC and adenoma, Dr. Kraus reported. The protein levels were approximately 2000?OD/mm2 in normal subjects and 12,000?OD/mm2 in patients with either adenomas or cancer.

The sensitivity for the detection of CRC was 92.3% and for adenomas was 75.0%. The specificity for each, respectively, was 83.8% and 89.2%. In the analysis of both groups combined, sensitivity was 78.4% and specificity was 86.8%.

Pancreatic Cancer Also Detected Early

In another study, an immunoassay showed promise for detecting early-stage pancreatic cancer with a high degree of accuracy. The assay identifies and quantifies serum PAM4 protein, an antigen that is present in nearly 90% of pancreatic cancers but is not typically observed in association with benign lesions or other malignancies.

"We found that the PAM4 protein is quite accurate at identifying patients with pancreatic cancer and, if validated in larger studies, would be a promising tool for detecting the disease when our potentially curative procedures have a better chance for a good outcome," said David V. Gold, PhD, from the Garden State Cancer Center in Belleville, New Jersey. The study was done in collaboration with Johns Hopkins Medical Institutes in Baltimore, Maryland.

The PAM4 monoclonal antibody, also known as clivatuzumab, identifies a unique biomarker with a high specificity for a mucin glycoprotein expressed by pancreatic adenocarcinoma. The protein is not detectable in normal pancreatic cells or in cells of patients with chronic pancreatitis, a condition that can be otherwise hard to distinguish from cancer.

"The PAM4 test has the ability to detect PAM4 antigen in the blood, a protein produced by the tumor that may act as a marker, not only for diagnosis but for targeted therapies," Dr. Gold told media representatives.

The PAM4 enzyme immunoassay was performed on 68 patients who had undergone pancreatic surgery and 19 healthy controls. Its overall sensitivity for detecting pancreatic cancer was 81%; it has 62% sensitivity for detecting stage?I pancreatic cancer, 86% sensitivity for stage?II disease, and 91% sensitivity for stage?III/IV disease, Dr. Gold reported.

"The PAM4 assay detected the overwhelming majority of patients with early-stage pancreatic cancer and 91% with late-stage disease," he said. "PAM4 is very specific for pancreatic cancer. It indicates a high possibility that a patient will have pancreatic cancer."

Dr. Gold predicted that the test will not be used for universal screening, but would best be applied to individuals suspected of having cancer or deemed to be at high risk for pancreatic cancer. This includes people with long-term chronic pancreatitis and diabetes, heavy smokers and drinkers, and those with a family history of hereditary forms of pancreatitis or pancreatic cancer, he said.

At the meeting, Samir Hanash, MD, head of molecular diagnostics at the Fred Hutchinson Cancer Research Center in Seattle, Washington, presented an invited lecture on pancreatic cancer biomarkers. He told Medscape Oncology that "quite a few markers behave like [PAM4]," and questioned how the test would perform earlier in the disease process, (i.e., in the premalignant or microinvasive disease state).

"If the application is for early detection, then it is not sufficient to declare victory," he maintained. "It would have to perform at an earlier stage." He added that no 1 biomarker is likely to offer an effective means of early detection because "no 2 tumors are the same." Instead, he said, "we are moving toward establishing panels" of proteins to increase both sensitivity and specificity, and he indicated that PAM4 is included in a panel that is being evaluated by his research group.

Further Development Underway

Both investigators indicated their assays are being further developed and might be clinically applicable within 2 to 3 years.

Robert Sticca, MD, professor of surgery at North Dakota School of Medicine and Health Sciences in Grand Forks, who moderated the press briefing, explained that these investigations are part of a larger research effort to develop tests that are highly accurate for detecting gastrointestinal cancers at an early stage.

"For pancreatic cancer, the medical profession has long struggled with the treatment of this disease, and these are very exciting data. If we had a test to detect it earlier, we would certainly do much better at managing it and preventing deaths," he said.

"The colorectal data are also preliminary, but if this test can be validated, it should be very beneficial in preventing deaths from this very common form of cancer."

The researchers have disclosed no relevant financial relationships.

2010 Gastrointestinal Cancers Symposium: Abstracts OP162 and 135. Presented January 22-24, 2010.

    
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