從CA19-9閑談胰腺癌早期診斷的分子標記物

08-17

11 人贊了文章

胰腺癌難以早期診斷是一個世界性的難題，NIH 還為此專門設立了大型合作研究計劃。這裡我想說的是3個分子，醫院常用的癌症表面抗原蛋白CA19-9, 天才高中生Jack Andraka選用的mesothelin, 以及已經通過2期臨床試驗的THBS-2/CA19-9雙重標記檢測。想看八卦的讀者可以離開了，下面的文字是寫給醫學領域的專業人士和患者家屬看的。

先說 CA19-9, 知乎上有醫院公眾號說這是檢驗胰腺癌的金標準，我需要說的是，這樣的醫院千萬別去，水平太低。以下是我們醫院胰腺癌中心官網對CA19-9的介紹：

Accuracy:

CA19-9 is elevated in the blood of 50-75% of individuals with PC. Other blood tests such as CEA are not as accurate. Supplemental imaging studies and tissue samples are required with CA19-9 levels for a definitive diagnosis.

CA19-9 can be used to track treatment progress of previously diagnosed PC patients. This blood test in conjunction with periodic CT scans will show whether the cancer is in remission or is continuing to grow.

Results:

If your doctor suspects pancreatic cancer, an abnormal CA 19-9 blood level will increase the suspicion. However, there are benign diseases of the bile ducts and pancreas that occasionally result in elevated CA 19-9 levels. For this reason CA 19-9 is not considered a diagnostic test.

CA19-9的最大問題是在胰腺炎和腸癌病人裡面也會顯著升高，專一性不好，容易誤診，所以無法作為胰腺癌的早期診斷標記物，倒是可以作為後期治療療效評估的標準之一。

再說天才高中生Jack Andraka選用的mesothelin, 這孩子為了申請專利，相關結果一直沒有公開發表，所以受到學術界的廣泛質疑。

後來有人邀請了5位專家對他的研究進行評審，其中一位是哈佛大牛George Church, 我曾經向他實驗室要過他第一篇CRISPR Science 文章的質粒進行CRISPR技術的測試，他的江湖地位無人質疑。

Andraka』s 「168 times faster, 26,667 times less expensive, and 400 times more sensitive」 figures are based on a comparison with ELISA. But Church saw problems with the way that Andraka characterizes the ELISA test.

下面是George Church的評審意見：

Test speed: Andraka says he compared the speed of his test to the amount of time he spent trying to get results from an ELISA kit he ordered online: 14 hours. But usually a modern ELISA test takes 1 hour.

Test cost: Andraka is comparing the commercial cost for a test – including the manufacturer』s profit and overhead – to his own materials cost. That』s not a fair comparison. He says the only mesothelin test that he found cost $912 per kit. But other ELISA tests are for sale online for $400 per 60 tests or $600 for 96 tests – in other words, about $6.50 per test run. That still compares favorably to Andraka』s $3 per 10 tests, but remember that there would also be a commercial markup if a company decided to sell his tests.

Sensitivity: Church felt that the standard deviations on Andraka』s sensitivity measurements were too big to say that his test is much more sensitive than ELISA. Others said that its not clear how much increased sensitivity a new test would need.

另外的4位專家對使用mesothelin有保留意見，提到CA19-9.

Is it the right protein?Another question: Is Andraka even testing for a protein that will effectively identify pancreatic cancer? Doctors use a blood protein called CA19-9 to track whether a pancreatic tumor is growing, or whether it will come back. But they don』t use CA19-9 for screening, because it would miss too many cancers and, more importantly, identify pancreatic cancer in patients who don』t have it. That could lead to unnecessary CAT scans, or even to unnecessary surgeries to remove tumors that don』t exist.

補充一下， Jack Andraka在Johns Hopkins University的指導老師也建議他加上其他的蛋白增強敏感性和準確性。

因為受到學術界的質疑，Jack Andraka申請專利，聯繫藥廠將他研究結果產業化的努力進展非常緩慢。

最後講到學術界的意見，國立癌症研究所最近高度評價了Kenneth Zaret 的早期胰腺癌篩查突破性工作。

Test Shows Promise for Pancreatic Cancer Early Detection?

www.cancer.gov

文章發表在去年的Science Translational Medicine 上，包括一期和二期的臨床試驗結果。

結果表明， THBS2和CA19-9雙重標記物對於胰腺癌的早期篩查，敏感度是87%，專一性是98%，這比單獨使用專一性不高的CA19-9要好很多。