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Cholecystokinin Type A Receptor Expression is Correlated with Poor Survival in Patients with Colon Cancer

膽囊收縮素A型接受器的表現與大腸癌患者生存率的相關性

摘要


背景與目的:膽囊收縮素A型接受器(CCKAR)已知在不同的惡性腫瘤中有過度表現的報告,但是對於此一過度表現與大腸癌之間關係的了解仍相當有限。因此,本研究擬針對膽囊收縮素A型接受器在大腸腫瘤組織中的表現,與大腸癌患者的存活率進行探討。實驗方法:利用免疫組織染色法,進行從49為大腸癌患者切除下來的剩餘檢體,進行膽囊收縮素A型接受器的定性與半定量分析。同時搭配其臨床資料進行相關性的統計分析。實驗結果:本研究結果顯示,膽囊收縮素A型接受器在細胞質與細胞核的表現,與大腸癌患者的性別、腫瘤分期與病程進展無顯著意義。但是膽囊收縮素A型接受器在細胞核的表現卻與患者一年存活率有顯著相關(P=0.032),核染色的表現越強,一年存活率越低。研究結論:本研究首次發現膽囊收縮素A 型接受器會轉移到細胞核,且核染色越強其一年存活率越差。這些研究結果暗示著膽囊收縮素A型接受器在大腸腫瘤癌化的過程中,可能扮演著重要且未知的角色。

並列摘要


Background and purpose: Cholecystokinin (CCK) and the gastrin receptors, CCKAR and CCKBR, are overexpressed in different malignancies of the human digestive tract; however, limited information is available regarding the correlation of their expression in colon cancer. The present study aimed to investigate whether the levels of expression of CCKAR and CCKBR were associated with the clinicopathological features of patients with colon cancer. Methods: CCKAR and CCKBR expression levels were determined using immunohistochemical analysis. Samples obtained from 49 surgical specimens were used for pathological examinations. Results: Cytoplasmic and nuclear staining of CCKAR was detected in 78% and 49% of samples, respectively, and did not correlate with the patients’ sex, tumor grade, or stage of tumor progression. However, strong nuclear, but not cytoplasmic, staining of CCKAR was significantly associated with relatively poor 1-year survival (P = 0.032). In contrast to CCKAR, weak to moderate staining of cytoplasmic CCKBR was detected in 84% of samples. Further, CCKBR stained weakly in the nucleus. Cytoplasmic CCKBR correlated only to the stage of tumor progression (P = 0.048). There was no significant association of nuclear CCKBR expression with patients’ clinicopathological characteristics. Conclusions: Our results show that cytoplasmic CCKBR expression and nuclear CCKAR expression were associated with the stage of tumor progression and 1-year survival, respectively. These findings suggest that CCKAR could serve as a potential marker for poor prognosis of patients with colon cancer and may play an unknown role in colon carcinogenesis.

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