Turkish Journal of Gastroenterology
Gastrointestinal Tract - Original Article

Clinicopathological and Prognostic Significance of Klotho and Estrogen Receptors Expression in Human Hepatocellular Carcinoma


Department of Gastroenterology, The People’s Hospital of Lianshui, Huaian, China


Medical Center for Digestive Diseases, The Second Affiliated Hospital, Nanjing Medical University, China


Department of Gastroenterology, The Fourth Affiliated Hospital, Nanjing Medical University, Nanjing, China


Digestive Endoscopy Department, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China

Turk J Gastroenterol 2021; 32: 828-836
DOI: 10.5152/tjg.2021.19986
Read: 1001 Downloads: 398 Published: 01 October 2021

Background: Hepatocellular carcinoma (HCC) is male-predominant cancer, but the underlying mechanism remains unclear. This study aimed to investigate the expression of the age-suppressing gene klotho and estrogen receptors (ERs) in HCC patients and analyze their association with clinicopathological variables and their effects on prognosis.

Methods: The expression patterns of klotho, ERα, and ERβ were determined by tissue microarray and immunohistochemical technique, and their correlations with clinicopathological characteristics were investigated using univariate and multivariate analysis.

Results: Klotho expression was significantly lower in HCC than in the adjacent noncancerous tissues (52.7% (49/93) vs. 90.8% (79/87), P = .000), and its protein level in HCC tissue was negatively correlated with clinical staging, histological grade, and stage of the primary tumor (T) (P < .05). Whereas the expression of nuclear ERα and ERβ was higher in HCC than their corresponding non-neoplastic tissues (55.9% (52/93) vs. 35.6% (31/87), P = .006; 59.1% (55/93) vs. 43.7% (38/87), P = .038), and the level of nuclear ERα and ERβ in HCC tissue was inversely correlated with T stage, tumor size, and clinical staging (P < .05). Correlation analysis showed the expression level of klotho, which is positively correlated with that of nuclear ERα (r = 0.243, P = .019). Patients with klotho-positive tumors had longer survival than those with klotho-negative tumors (P = .002). Cox proportional hazards model analysis demonstrated that positive expression of klotho was an important factor indicating good prognosis (P = .003).

Conclusion: Klotho, partially regulated by ERα-mediated estrogen pathway, acts as a tumor suppressor and might be a novel biomarker candidate for predicting progression and prognosis in HCC patients.

Cite this article as: Huang S, Wang W, Cheng Y, Lin J, Wang M. Clinicopathological and prognostic significance of Klotho and estrogen receptors expression in human hepatocellular carcinoma. Turk J Gastroenterol. 2021; 32(10): 828-836.

EISSN 2148-5607