TXNRD1 Is an Unfavorable Prognostic Factor for Patients with Hepatocellular Carcinoma

Abstract

Thioredoxin reductase 1 (TXNRD1) which is a selenocysteine-containing protein is overexpressed in many malignancies. Its role in the hepatocellular carcinoma (HCC) prognosis has not been investigated. In this study, we investigated whether TXNRD1 functions as an independent prognostic factor for HCC patients. We found TXNRD1 was overexpressed in HCC tissues and cells, immunohistochemical analysis suggested TXNRD1 was elevated in 57 of 120 (47.5%) clinical samples, and its level was increased with the increasing clinical stage. In addition, TXNRD1 expression was positively correlated with clinical stage (p = 3.5e − 5), N classification (p = 4.4e − 4), and M classification (p = 0.037) of HCC patients. Kaplan-Meier analysis revealed that patients with high TXNRD1 expression had significantly shorter survival time than patients with low TXNRD1 expression. Multivariate analysis found TXNRD1 was an independent prognostic factor for HCC patients. In conclusion, our data suggested that TXNRD1 was a biomarker for the prognosis of patients with HCC.

Induction of Oxidative Stress Through Inhibition of Thioredoxin Reductase 1 Is an Effective Therapeutic Approach for Hepatocellular Carcinoma

“…Fu et al found TXNRD1 to be overexpressed in HCC clinical samples and cells. Their study further showed high TXNRD1 expression to be positively correlated with advanced tumor staging and poorer survival in HCC patients, suggesting that TXNRD1 is a an unfavorable prognostic marker . Besides, the significant relationship between TXNRD1 expression and human HCC suggested it as a therapeutic target, which has been delineated in our study.…”

“…TXNRD transfers the electron to TXN, which then transfers the electron for ROS scavenging. TXN is a major cellular protein disulfide reductase, serving as an electron donor to disulfide groups in peroxiredoxins, another group of antioxidant molecules for the reduction of H 2 O 2 and peroxides, as well as a ribonucleotide reductase for DNA replication and repair and methionine sulfoxide reductase . The thioredoxin system is essential for reduction‐oxidation (redox) homeostasis and protects DNA from oxidative stress–associated DNA damage.…”

“…We recently identified the folate cycle as a major producer of NADPH to counteract oxidative stress in human HCC, and specific inhibition of a key folate cycle enzyme, methylenetetrahydrofolate dehydrogenase 1‐like, or a folate analogue, methotrexate, sensitizes HCC toward sorafenib treatment in vitro and in vivo . TXNRD1 has been suggested as a prognostic marker for human HCC patients . Increased expression of TXNRD1 in clinical samples positively correlated with advanced clinical staging and poorer patient survival …”

“…TXNRD1 has been suggested as a prognostic marker for human HCC patients . Increased expression of TXNRD1 in clinical samples positively correlated with advanced clinical staging and poorer patient survival …”

Association between loss of Y chromosome and poor prognosis in male head and neck squamous cell carcinoma

“…Disruption of redox homeostasis, resulting in elevated levels of reactive oxygen species in tumor cells has been implicated in the promotion of tumor progression and development of drug resistance . Genes upregulated in LoY compared with non‐LoY cases included members of the AKRs superfamily of NAD(P)H‐linked oxidoreductases, such as AKR1B10, AKR1C1, AKR1C2, AKR1C3, as well as ALDH3A1, G6PD, GPX2, PIR, SRXN1, and TXNRD1, which are increasingly recognized for their important roles in drug detoxification and xenobiotic metabolism . In particular, the upregulation of AKR1C1, AKR1C2, and G6PD are all associated with resistance to cisplatin‐based chemotherapy in lung cancer, whereas upregulation of AKR1C3 is linked to insensitivity to radiotherapy in oesophageal cancer .…”