Upregulation of Anaphase Promoting Complex (APC) 7 as a Prognostic Marker for Esophageal Squamous Cell Carcinoma: A Hospital Based Study

Abstract

Esophageal cancer is the sixth leading causes of cancer death with esophageal squamous cell carcinoma (ESCC) to be the most prevalent type worldwide and has poor prognosis due to late diagnosis. Dysregulation of Anaphase Promoting Complex (APC)/cyclosome\xa0 activation due to altered expression of APC molecules lead to perturbed mitotic progression and \xa0malignancy. The study involves expression analysis of the four different subunit of APC/C complex – APC3, APC4, APC5 and APC7, analyzed by real-time RT-PCR which was then correlated with the clinicopathological parameter and different lifestyle factors. Divergent APC3 expression pattern in blood and tissue sample is suggestive of its role as a Tumor suppressor gene. Further evident from its significant association (p=0.04<0.05) with node stage advancement and metastasis in tissue sample apart from its association with life style factor such as duration of smoking, betel nut chewing, and\xa0 tobacco consumption (p<0.05). Significant up regulation of APC 7 (tissue and blood, N=38, 3.211 ± 2.391and 387.428 ± 3.145 respectively) and APC5 (tissue and blood, N=62 & 60, 5.694 ± 4.805 and 4.927±4.367 respectively) is suggestive of their role in uncontrolled cell proliferation. Their significant association with tumor size, node stage (p<0.05) and degree of differentiation (p=0.01<0.05) apart from its association with increasing age supports their potential role in tumorigenic transformation in ESCC. Further a number of exclusive life style associated factors also plays an important supporting role towards the development of ESCC in the Northeast Indian population.\xa0\xa0Analysis based on the Pearson s correlation coefficient indicated the positive correlation between APC3 and APC4, APC3 and APC7 gene expression in tissue, APC3 and APC5 in blood samples. Also we have observed a positive correlation between APC7 expression in blood and tissue samples that may serve as prognostic biomarkers. \n \nFunding Information: The author acknowledges financial support from Department of Health Research Government of India vide Sanction Number R.12016/01/2017-HR dtd: 20/02/2018. The author acknowledges MHRD funded TEQIP-III programme for Research Assistantship. \n \nDeclaration of Interests: None. \n \nEthics Approval Statement: This study was approved by the institutional review board of the Gauhati Medical College and Hospital, Guwahati, Assam and all procedures performed in studies were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declarations. All patients gave written informed consent.