Upregulation of anaphase promoting complex (APC) 7 as a prognostic marker for esophageal squamous cell carcinoma: A hospital based study

Eyashin Ali; Manash Jyoti Kalita; Simanta Kalita; Jayasree Talukdar; Ankur Jyoti Deka; Jasmin Sultana; Bikash Narayan Choudhury; Munindra Narayan Baruah; Sahana Bhattacharjee; Subhash Medhi

doi:10.1016/j.heliyon.2022.e09722

Upregulation of anaphase promoting complex (APC) 7 as a prognostic marker for esophageal squamous cell carcinoma: A hospital based study

Heliyon. 2022 Jun 12;8(6):e09722. doi: 10.1016/j.heliyon.2022.e09722. eCollection 2022 Jun.

Authors

Affiliations

¹ Department of Bioengineering and Technology, Laboratory of Molecular Virology and Oncology, GUIST, Gauhati University, Guwahati, Assam, India.
² Department of Gastroenterology, Gauhati Medical College Hospital, Guwahati, Assam, India.
³ Department of Head and Neck Oncology, North East Cancer Hospital and Research Institute, Jorabat, Guwahati, India.
⁴ Department of Statistics, Gauhati University, Guwahati, Assam, India.

Abstract

Esophageal cancer is the sixth leading cause of cancer death, and esophageal squamous cell carcinoma (ESCC) is the most prevalent type worldwide, with a poor prognosis due to late diagnosis. The search for new molecular prognostic biomarkers revealed that dysregulation of anaphase promoting complex/cyclosome (APC/C) activation due to altered expression of APC molecules might lead to perturbed mitotic progression leading to malignancy. We analyzed the expression of the four different subunits of the APC/C complex-APC3, APC4, APC5 and APC7-by Real Time Polymerase Chain Reaction (RT-PCR). The findings were then correlated with clinicopathological parameters and different lifestyle factors. Significant upregulation of APC7 (tissue and blood: N = 50; 3.72 ± 1.21 and 4.45 ± 1.18, respectively) and APC3 (tissue and blood: N = 52 and 55 and 4.50 ± 1.41 and 4.58 ± 1.06, respectively) suggests their role in uncontrolled cell proliferation. In addition to their association with increasing age, their significant association with tumor size, node stage (only APC7 (p < 0.05)), and dysphagia grade supports a potential role in tumorigenic transformation in ESCC. Furthermore, several exclusive lifestyle-associated factors play a crucial supporting role in the development of ESCC in the Northeast Indian population. Various lifestyle factors, such as the duration of smoking, tobacco and betel nut consumption, and the duration of alcohol consumption, are significantly associated with the expression of APC. Analysis based on Pearson's correlation coefficient indicated a positive correlation among the gene expression levels ofAPC3 (both blood and tissue), APC5 (tissue) and APC3 (tissue), APC7 (tissue) and APC3 (tissue), and APC7 (tissue) and APC3 (blood). Additionally, a positive correlation was found between APC7 expression in blood and tissue samples. However, no significant correlation was found between APC 7 expression and APC4 and APC5 expression in either blood or tissue samples.

Keywords: Anaphase-promoting complex-cyclosome; Cell cycle; ESCC; Gene expression.