遺傳學標記可以有助於診斷前列腺增生

511個基因發生變異可預示有症狀和無症狀性BPH和癌症

  2002年6月5日報導─在《Proceedings of the National Academy of Science》雜誌5月28日一期中列出了511個基因,可以有助於前列腺增生的診斷。正常的前列腺、有症狀或無症狀的良性的前列腺增生(BPH)、和癌症都有不同的遺傳標記。

  在新聞發表會上,主要作者,比茲堡大學醫學部的Robert Getzenberg博士說:「我們已知並不是所有的BPH都是一樣的,患者表現不同程度的前列腺增生和症狀,從沒有任何症狀到出現腎功能衰竭。但我們不知道為什麼。」

  在沒有發現遺傳標記的差異之前,所有的患者都按相似的方法進行治療,這常常是昂貴而沒有效果的治療方式。Getzenberg說:「現在我們可以針對不同亞型的BPH,採用新的治療方法,根據他們的疾病特點來緩解這種疾病的症狀。」

  為了區分BPH患者的分子差異,研究者們利用基因晶片的技術分析了在前列腺組織發育區域的基因的表達情況。他們發現了511個基因,在來自10名沒有發生BPH的正常對照、5名患有無症狀性BPH患者、8名患有症狀性BPH患者、和8名患有BPH合併癌變的患者的組織樣本中存在表達的差異。

  主成分分析(PCA)的結果顯示,這4組患者可以清楚的加以區分。患有症狀性BPH的男性患者,其前列腺的組織學變化,與患有前列腺癌的個體,其BPH區域的變化非常相似,這提示這兩種情況可能存在關聯,並且支持在前列腺癌發病中存在基因「背景效應」的理論。

  用於鑒別各個組的獨特的基因群包括與細胞增生有關的基因,這些基因在症狀性BPH組患者中出現表達的提高、和一些包括原癌基因的基因,這些基因在BPH伴有癌變的患者中出現表達的上調。那些將症狀性BPH和BPH伴有癌變的患者區別於正常的和無症狀的患者的基因,還包括炎症調控因數、細胞激酵素、和細胞外間質相關的分子。還有一些功能不清的基因可以區分出非症狀性BPH。

  Getzenberg說:「這些發現中最吸引人的地方是,發現了炎症與症狀性BPH之間強的關聯。得到這些資訊後,我們現在可以發明一些新的治療方法,例如采用抗炎症的藥物來緩解患者的症狀。」

  由於JM27,一種在前列腺癌中表達升高,並且在前列腺組織和女性生殖器官特異性表達的基因,會在症狀性BPH患者中出現表達的上調,因此JM27的過度表達可能參與BPH、前列腺癌、和女性生殖道腫瘤的發展。

  UCPI全面預防前列腺和泌尿系統腫瘤研究計劃的負責人,Joel B. Nelson醫師說:「基因表達模式的研究是一個非常有力的研究工具。它已經為這種疾病發病的本質提供了重要的線索,這使得我們在治療中能採用更有策略的方法。」

Genetic Signature Helps Diagnose Enlarged Prostate

511 Genes Distinguish Normal, Symptomatic/Asymptomatic BPH, Cancer

By Laurie Barclay, MD
WebMD Medical News

Reviewed by Gary D. Vogin, MD

June 5, 2002 -- A set of 511 genes described in the May 28 issue of the Proceedings of the National Academy of Science can help diagnose the cause of prostate enlargement. Normal prostate, benign prostatic hypertrophy (BPH) with or without symptoms, and cancer each have a distinct genetic signature.

"We have known that not all BPH is the same; patients experience different degrees of prostate enlargement and experience different symptoms, ranging from none to renal failure, but we didn't know why," senior author Robert Getzenberg, PhD, from the University of Pittsburgh School of Medicine, says in a news release.

Before the discovery of genetic differences, all patients were treated in a similar manner, which was often both costly and ineffective. "Now, we can look into targeting the different types of BPH and creating new therapies to alleviate the symptoms of the disease based upon their unique properties," Getzenberg says.

To determine the molecular differences underlying BPH, the researchers analyzed gene expression profiles from prostate transition zone tissue using microarrays. They identified a set of 511 genes that were differentially expressed in tissue samples taken from four groups of patients: 10 normal controls without BPH, 5 patients with asymptomatic BPH, 8 patients with symptomatic BPH, and 8 patients with both BPH and cancer.

Principal component analysis (PCA) showed that the 4 groups were clearly distinguishable from each other. The prostates of the group of men with symptomatic BPH were most similar to the areas of BPH in individuals with prostate cancer, suggesting a possible link between the 2 conditions and supporting the concept of a genetic "field effect" in prostate cancer.

Unique sets of genes identifying each group included genes associated with cell proliferation, which were upregulated in the symptomatic BPH group, and a series of genes including oncogenes, which were upregulated in the BPH-cancer group. Subsets of genes including inflammatory mediators, cytokines, and extracellular matrix-associated molecules distinguished the symptomatic BPH and BPH with cancer from the normal and asymptomatic groups. A cluster of genes with unknown function distinguished the asymptomatic BPH.

"One of the most striking of these discoveries is the strong correlation between inflammation and symptomatic BPH," Getzenberg said. "With this information, we can now investigate new therapeutic approaches, such as using anti-inflammatory agents to alleviate symptoms."

Since JM27, a gene upregulated in prostate cancer and specific to the prostate and female reproductive tissues, was upregulated in symptomatic BPH, overexpression of JM27 may be involved in the progression of BPH, prostate cancer, and tumors of the female reproductive tract.

"Studying patterns of gene expression is a powerful tool," said Joel B. Nelson, MD, co-director of the Comprehensive Prostate and Urologic Cancer Program at UPCI. "Already it is providing important clues about the fundamental nature of disease, which will allow us to more strategically target our therapies."

© 2002 WebMD Inc. All rights reserved.

    
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