Increased expression of stathmin and elongation factor 1α in precancerous nodules with telomere dysfunction in hepatitis B viral cirrhotic patients

Abstract

BackgroundTelomere dysfunction is important in carcinogenesis, and recently, stathmin and elongation factor 1α (EF1α) were reported to be up-regulated in telomere dysfunctional mice.MethodsIn the present study, the expression levels of stathmin and EF1α in relation to telomere length, telomere dysfunction-induced foci (TIF), γ-H2AX, and p21WAF1/CIP1 expression were assessed in specimens of hepatitis B virus (HBV)-related multistep hepatocarcinogenesis, including 13 liver cirrhosis specimens, 14 low-grade dysplastic nodules (DN), 17 high-grade DNs, and 14 hepatocellular carcinomas (HCC). Five normal liver specimens were used as controls. TIF were analyzed by telomere fluorescent in situ hybridization (FISH) combined with immunostaining, while the protein expressions of stathmin, EF1α, γ-H2AX, and p21WAF1/CIP1 were detected by immunohistochemistry.ResultThe expressions of stathmin and EF1α gradually increased as multistep hepatocarcinogenesis progressed, showing the highest levels in HCC. Stathmin mRNA levels were higher in high-grade DNs than normal liver and liver cirrhosis, whereas EF1α mRNA expression did not show such a difference. The protein expressions of stathmin and EF1α were found in DNs of precancerous lesions, whereas they were absent or present at very low levels in normal liver and liver cirrhosis. Stathmin histoscores were higher in high-grade DNs and low-grade DNs than in normal liver (all, P < 0.05). EF1α histoscores were higher in high-grade DNs than in normal liver and liver cirrhosis (all, P < 0.05). Stathmin mRNA levels and histoscores, as well as EF1α histoscores (but not mRNA levels), were positively correlated with telomere shortening and γ-H2AX labeling index (all, P < 0.05). EF1α histoscores were also positively correlated with TIF (P < 0.001). Significantly greater inactivation of p21WAF1/CIP1 was observed in low-grade DNs, high-grade DNs, and HCC, compared to liver cirrhosis (all, P < 0.05). p21WAF1/CIP1 labeling index was inversely correlated with TIF, stathmin mRNA level, and EF1α histoscore (all, P < 0.05).ConclusionStathmin and EF1α are suggested to be closely related to telomere dysfunction, DNA damage, and inactivation of p21WAF1/CIP1 in HBV-related multistep hepatocarcinogenesis. Accordingly, assessment of stathmin and EF1α levels as a reflection of telomere dysfunction may be helpful in evaluating the biological characteristics of precancerous hepatic nodules in hepatitis B viral cirrhotic patients.

Comparative proteomic analyses of the parietal lobe from rhesus monkeys fed a high-fat/sugar diet with and without resveratrol supplementation, relative to a healthy diet: Insights into the roles of unhealthy diets and resveratrol on function

“…Therefore, the levels of stathmin may directly affect microtubule turnover and dynamics. Moreover, an overexpression of stathmin is found to be present in various forms of cancers and in AD progression, while also being positively correlated to telomere shortening [35,36]. In the current study, monkeys fed HFS+RSV have a 0.69-fold decrease of stathmin compared to HFS fed monkeys.…”

Stathmin-dependent molecular targeting therapy for malignant tumor: the latest 5 years’ discoveries and developments

“…We emphatically harvested the lasted 5 year studies on this field. As shown in Table 1 , stathmin is highly expressed in a variety of assessed human malignancies including lung cancer [ 3 , 11 ], esophageal carcinoma [ 12 – 16 ], breast cancer [ 17 ], cholangiocarcinoma [ 18 ], hepatocellular carcinoma [ 4 , 19 , 20 ], gastric cancer [ 21 – 25 ], pancreatic cancer [ 26 – 28 ], myelodysplastic syndromes [ 29 ], nasopharyngeal carcinoma [ 30 ], malignant pleural mesothelioma [ 31 ], cervical carcinomas [ 32 ], endometrial carcinoma [ 33 , 34 ], urothelial carcinoma of the bladder [ 35 – 37 ], colorectal cancer [ 38 ] and glioblastoma [ 39 ]. And, high expression of stathmin intimately correlates with the malignant behavior and clinical features of tumor.…”

A Bioinformatics Analysis Identifies the Telomerase Inhibitor MST-312 for Treating High-STMN1-Expressing Hepatocellular Carcinoma

“…In addition, a slight increase of STMN1 mRNA was found in precancerous liver tissues (cirrhosis and dysplasia), suggesting that STMN1 may play an early role during hepatocarcinogenesis. Previous studies consistently suggest that protumorigenic overexpression of STMN1 is associated with hepatocarcinogenesis [ 16 , 43 , 44 ].…”