肝癌為全世界常見的惡性的癌症之一，除了其致死率高以外，其發生率也是逐年攀升。在臨床上治療肝癌的方式通常是利用手術切除搭配化學療法，然而這樣的治療方式對於肝癌病人的死亡率並無法有效地改善。因此，研究更有效治療肝癌的方式以及預防肝癌轉移有助於提升肝癌病人的存活率。近來研究認為在癌細胞裡有一小族群的細胞具有自我更新及分化的能力，並且是造成癌症發生的一個重要因素，將其定義為癌症幹細胞(Cancer stem cells,CSCs)。因此探討癌症幹細胞相關訊息傳遞有助於提供治療癌症成功率。CD90已被視為是肝癌的癌症幹細胞標記(cancer stem cell marker)。然而過去的文獻卻指出CD90在卵巢癌扮演抑癌基因的角色。因此我們透過生物資訊工具Oncomine去分析CD90在20種癌症的信使核醣核酸(messenger RNA)的表現量。確實發現CD90在臨床肝癌病人的表現量上升，且CD90高表現與預後較差相關，相反地在卵巢癌表現量下降，而CD90高表現預後較好。因此我們更進一步分析CD90在肝癌或卵巢癌的共表達基因(co-expressed genes)，發現在肝癌中CD90共表達基因大多數為致癌基因(oncogene)，相反地在卵巢癌CD90共表達基因則是過去被報導為抑癌基因。因此我們更進一步比較CD90在八種不同癌症中的共表達基因。在這八種癌症中CD90都傾向於扮演致癌基因。利用即時聚合酶鏈式反應(q-PCR)偵測共表達基因在穩定表現CD90細胞株中表現量。THBS2和VCAN表現量在穩定表現CD90中的表現量上升。當我們在過量表現CD90的肝癌細胞株抑制THBS2會降低在軟性瓊膠(soft agar)上的生長，顯示THBS2在參與CD90 所誘發癌化 (carcinogenesis)。此外我們透過IPA預測CD90可能透過鈣離子和MMP2以及HTT影響THBS2，而CD90則可能透過FN1,TGFB1，鈣離子以及STAT3調控VCAN。

Liver cancer is one of the prevalent cancers with high mortality in the world. The cancer stem cell hypothesis defined that a small population of cancer cells with capacity to self-renew is responsible for tumor formation and relapse. CD90 is a Glycosylphosphatidylinositol-anchored cell surface protein and has been identified as a liver cancer stem cells marker. However, previous studies suggested that CD90 may act as tumor suppressor in ovarian cancer. Therefore, we analyzed the mRNA expression of CD90 in 20 common cancer by using Oncomine databases. The transcriptional level of CD90 is upregulated in liver cancer which is correlated with poor clinical outcome. Conversely, the transcription of CD90 in ovarian cancer is downregulated which is correlated with good prognosis. The profile of CD90 co-expressed genes in liver cancer revealed the oncogenic functional modules. The profile of CD90 co-expressed genes in ovarian cancer is correlated with tumor suppression. The CD90 co-expressed genes in liver, breast, gastric, pancreatic, lung, colon, lymphoma and esophageal cancer were identified and the mRNA expression was validated by q-PCR in liver cancer cell lines. THBS2 and VCAN were upregulated in CD90 transfectants. Knockdown of THBS2 decreased anchorage-independent growth, suggesting that THBS2 was important for CD90-mediated tumor progression. Furthermore, IPA analysis suggested that CD90 may affect THBS2 through calcium, MMP2 and HTT. CD90 may affect VCAN through calcium, STAT3, FN1 and TGFB1.

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