新的驗血方式可以非侵犯性檢測胃腸道癌症
作者：Roxanne Nelson
出處：WebMD醫學新聞
September 28, 2009 (德國柏林) —研究者在第15屆歐洲癌症組織研討會與第34屆歐洲腫瘤醫學會年會聯合研討會中報告指出，兩種新的驗血方式可以促進胃腸道癌症的診斷。
雖然尚屬初步研究結果，但這些檢測將可以提供一種非侵犯性、較簡便、更具成本效益的胃腸道腫瘤早期診斷方法。
西班牙巴塞隆納Vall d'Hebron大學醫院的Josep Tabernero醫師在Medscape Oncology聯繫進行專訪時表示，雖然這些報告相當有趣，仍有許多有待研究之處。
他表示，現在，它們用於診斷或一般篩檢的專一性不足。
【SYNE1與 FOXE1】
這兩種檢測之一是一種甲基化檢測，由比利時OncoMethylome Sciences公司產品研發副總裁Joost Louwagie博士等人所發展。研究顯示，DNA甲基化與蛋白質表現調節有關，關鍵基因的甲基化與腫瘤發生及分化都有關。
研究者檢測兩組血液樣本，每個都來自單一次的抽血，使用的血漿數量不一定。第一次檢測時，樣本來自124名大腸直腸癌病患與444名對照組。
DNA粹取與重亞硫酸鹽轉化方法獲得40%輸入DNA的復原。他們發現，兩個新報告的甲基化標記─SYNE1與FOXE1，在各階段的大腸直腸癌病患中出現的頻率相當高；這些甲基化基因在無癌症者很少見。
在檢測的第一個世代中，血漿數量從0.8 mL-4.3 mL；同時有SYNE1 與FOXE1的敏感性為58%，專一性為90%。
對69名大腸直腸癌病患與242名對照組進行第二次的獨立世代檢測；結果顯示，同時有兩種標記的敏感度為58%，專一性為91%。但是在血漿量至少有3.3 mL的樣本中，敏感度增加到77%。
Louwagie博士表示，增加血漿量似乎可以有更好的敏感度，此效果在初期病患更為強烈。
根據這些結果，研究者現在準備進行大型的確效研究，目前正於一個前瞻性大腸直腸癌篩檢研究招募研究對象。目標是在2009年底前納入7000人。
Louwagie博士指出，這個檢測方式並不表示要取代大腸鏡，但是一旦獲得確認，此方式可以作為無法或拒絕進行大腸鏡篩檢者的替代方法。甲基檢測可以在例行體檢時進行，可有助於確認哪些病患需轉介進行大腸鏡檢查。
【S100A4 mRNA】
第二個新檢測方法是一種偵測血漿中S100A4 mRNA轉譯程度的分析，此方法由德國柏林Charite醫學大學以及Max Delbruck分子醫學中心的Ulrike Stein醫師等人發展。
這項檢測可以幫助診斷大腸、直腸、胃癌，也可以幫助預測已經有前述診斷之病患的轉移可能性。Stein醫師解釋，已知S100A4是一種轉移擴張因子，偵測原發腫瘤中的S100A4 mRNA 具有診斷和預後相關性。
Stein醫師表示，S100A4是與轉移有關的最初幾個標記之一，它是多種腫瘤惡化與不佳預後的一種標記。
Stein醫師解釋，本研究的目標是確認大腸、直腸、胃癌病患血漿樣本中S100A4轉譯之診斷和預後強度。每天從大腸癌病患(n= 185人)、直腸癌病患(n= 190人)、胃癌病患(n= 91人)蒐集血液樣本；另外也從51名健康志願者獲得對照組樣本。以定量特定基因兩步驟即時反轉錄酶PCR確認S100A4 mRNA值。
研究者在所有的血漿樣本偵測S100A4 mRNA 值，大腸、直腸、胃癌病患的值顯著高於對照組(P< .0001)。轉移大腸癌病患的值也比未轉移者高。
根據Stein醫師表示，S100A4值高與後來發生轉移有關。她表示，在追蹤時，最初血液樣本中S100A4值較高的病患，後來發生了轉移。
Stein醫師表示，S100A4轉譯作為胃腸道癌症篩檢工具是可以理解的，但是需要更大型的前瞻性研究。
Louwagi博士的研究接受Signature Diagnostics之贊助且與OncoMethylome Sciences公司合作。Stein醫師的研究接受柏林癌症協會的資金。
第15屆歐洲癌症組織研討會(ECCO 15)與第34屆歐洲腫瘤醫學會年會(34th ESMO)聯合研討會：摘要12 LBA與13LBA。發表於2009年9月21日。
New Blood Tests Offer Noninvasive Method of Detecting GI Cancers
By Roxanne Nelson
Medscape Medical News
September 28, 2009 (Berlin, Germany) — Two new blood tests might enhance the diagnosis of gastrointestinal cancers, researchers reported here at the 15th Congress of the European CanCer Organization and the 34th European Society for Medical Oncology Multidisciplinary Congress.
Although the results of the studies are still early, the tests could potentially offer a noninvasive, simpler, and more cost-effective means of diagnosing early gastrointestinal tumors.
When approached by Medscape Oncology for independent comment, Josep Tabernero, MD, from Vall d'Hebron University Hospital in Barcelona, Spain, said that although the papers were interesting, there were "several caveats to the studies."
"Right now, they are not specific enough for diagnosis," he said, "or for general screening."
SYNE1 and FOXE1
One of the 2 tests is a methylation test, developed by Joost Louwagie, PhD, vice president of product development at OncoMethylome Sciences in Leuven, Belgium, and colleagues. Research has demonstrated that DNA methylation is involved in the regulation of protein expression, and methylation of key genes has been associated with both initiation and proliferation of tumors.
The researchers tested 2 groups of blood samples, each obtained from a single blood draw, using varying amounts of plasma volume. In the first test, samples were obtained from 124 patients with colorectal cancer and 444 control subjects.
The extraction of DNA and bisulfite conversion methods resulted in recovery of about 40% of the input DNA. They found that 2 newly reported methylation markers, SYNE1 and FOXE1, had a high frequency in patients at all stages of colorectal cancer. These methylation genes occur infrequently in individuals without cancer.
In the first cohort tested, plasma volumes ranged from 0.8?mL to 4.3?mL; the sensitivity for the combination of SYNE1 and FOXE1 was 58% and specificity was 90%.
Testing was conducted in a second independent cohort of 69 patients with colorectal cancer and 242 control subjects. The results showed that sensitivity for the combined markers was 58% and the specificity was 91%. But in samples with at least 3.3?mL of plasma, the sensitivity increased to 77%.
"Increasing the volume did seem to give better sensitivity, and this effect was seen most strongly in patients with early-stage disease," said Dr. Louwagie.
On the basis of these results, the researchers are now preparing to conduct a large validation study and are currently enrolling participants in a prospective colorectal cancer screening study. The goal is to have 7000 people enrolled by the end of 2009.
Dr. Louwagie pointed out that this test is not meant to replace colonoscopy, but once it is validated, it can serve as an option for individuals who are either unable or who decline to undergo colonoscopy screening. The methylation test can be performed during routine physical exams and can help identify patients who should then be referred for colonoscopy.
S100A4 mRNA
The second new test is an assay that detects transcription levels of S100A4 messenger (m)RNA in plasma, which was developed by Ulrike Stein, MD, and colleagues, from Charite University Medicine Berlin and Max Delbruck Center for Molecular Medicine in Berlin, Germany.
The test might help diagnose colon, rectal, and gastric cancers, and might help predict the likelihood of metastatic disease in patients who have already been diagnosed. Dr. Stein explained that S100A4 is known to be a metastasis progressor, and the detection of S100A4 mRNA in several primary tumors is of diagnostic and prognostic relevance.
"S100A4 was cloned as one of the first markers associated with metastasis," said Dr. Stein. "It is a marker for advanced disease and poor prognosis for several tumors."
The goal of this study, explained Dr. Stein, was to define the diagnostic and prognostic power of S100A4 transcripts detected in plasma samples from colon, rectal, and gastric cancer patients. Daily blood samples were collected from patients with colon cancer (n?= 185), rectal cancer (n?= 190), and gastric cancer (n?= 91). Samples were also obtained from 51 healthy volunteers who served as control subjects. Levels of S100A4 mRNA were determined by quantitative gene-specific 2-step real-time reverse-transcriptase PCR.
The researchers detected S100A4 mRNA in all plasma samples that were analyzed, and levels were significantly higher in colon, rectal, and gastric cancer patients than in the control subjects (P?< .0001, respectively). Higher levels were also detected in colon cancer patients with metastatic disease than in those with nonmetastasized disease.
Higher levels of S100A4 were associated with the future development of metastases, according to Dr. Stein. "On follow-up, patients who had gone on to develop metastatic disease had higher levels of S100A4 on their initial blood samples," she said.
The S100A4 transcript can conceivably be used as a screening tool for gastrointestinal cancers, but larger prospective studies are needed, Dr. Stein said.
Dr. Louwagie's study was sponsored by Signature Diagnostics in collaboration with OncoMethylome Sciences. Dr. Stein's study was supported by a grant from the Berlin Cancer Society.
15th Congress of the European CanCer Organization (ECCO 15) and the 34th European Society for Medical Oncology (34th ESMO) Multidisciplinary Congress: Abstracts 12 LBA and 13LBA. Presented September 21, 2009.
