PLAT was as effective as surgical resection in the treatment of solitary and small HCC. PLAT had the advantage over surgical resection in being less invasive.

Hepatocellular carcinoma (HCC) is a highly heterogeneous disease, which makes the prognostic prediction challenging. Ferroptosis, an iron-dependent form of regulated cell death, can be induced by sorafenib. However, the prognostic value of ferroptosis-related genes in HCC remains to be further elucidated. In this study, the mRNA expression profiles and corresponding clinical data of HCC patients were downloaded from public databases. The least absolute shrinkage and selection operator (LASSO) Cox regression model was utilized to construct a multigene signature in the TCGA cohort. HCC patients from the ICGC cohort were used for validation. Our results showed that most of the ferroptosis-related genes (81.7%) were differentially expressed between HCC and adjacent normal tissues in the TCGA cohort. Twenty-six differentially expressed genes (DEGs) were correlated with overall survival (OS) in the univariate Cox regression analysis (all adjusted P< 0.05). A 10-gene signature was constructed to stratify patients into two risk groups. Patients in the high-risk group showed significantly reduced OS compared with patients in the low-risk group (P < 0.001 in the TCGA cohort and P = 0.001 in the ICGC cohort). The risk score was an independent predictor for OS in multivariate Cox regression analyses (HR> 1, P< 0.01). Receiver operating characteristic (ROC) curve analysis confirmed the signature's predictive capacity. Functional analysis revealed that immune-related pathways were enriched, and immune status were different between two risk groups. In conclusion, a novel ferroptosis-related gene signature can be used for prognostic prediction in HCC. Targeting ferroptosis may be a therapeutic alternative for HCC.

Mammalian telomeric DNA contains duplex TTAGGG repeats and single-stranded overhangs. POT1 (protection of telomeres 1) is a telomere-specific single-stranded DNA-binding protein, highly conserved in eukaryotes. The biological function of human POT1 is not well understood. In the present study, we demonstrate that POT1 plays a key role in telomeric end protection. The reduction of POT1 by RNA interference led to the loss of telomeric single-stranded overhangs and induced apoptosis, chromosomal instability, and senescence in cells. POT1 and TRF2 interacted with each other to form a complex with telomeric DNA. A dominant negative TRF2, TRF2⌬B⌬M , bound to POT1 and prevented it from binding to telomeres. POT1 overexpression protected against TRF2⌬B⌬M -induced loss of telomeric single-stranded overhangs, chromosomal instability, and senescence. These results demonstrate that POT1 and TRF2 share in part in the same pathway for telomere capping and suggest that POT1 binds to the telomeric single-stranded DNA in the D-loop and cooperates with TRF2 in t-loop maintenance.Human telomeres are specialized chromosomal terminal elements, containing tandem repetitive sequences and specific proteins. Telomeric DNA is mostly composed of 2 to 30 kb of double-stranded TTAGGG repeats, which are necessary for telomeric function in somatic cells (5,19,24,43). The termini of human telomeres carry an overhang (ϳ300 nucleotides) of single-stranded 3Ј DNA (38,41,56). In many eukaryotes, telomere length is maintained by telomerase, a reverse transcriptase that adds TTAGGG repeats onto the 3Ј ends of telomeres (5,8,39,43), which can counteract the loss of terminal sequences during DNA replication. This end replication problem of human telomeres has received particular attention for its implications in ageing and cancer (4,7,16,18,30,43,44,55). Maintenance of the telomeric TTAGGG repeats at human chromosome ends, either by telomerase (13) or by an alternative mechanism (9), is essential for immortalized cells in vitro to escape from the normal limitations of the proliferation capacity.Telomeres and capping proteins allow cells to distinguish natural chromosome ends from damaged DNA. The disruption of telomeric function can trigger a DNA damage response, including p53-dependent apoptosis (28). The overloading of DNA repair activities can also threaten the integrity of chromosome ends, thereby leading to extensive genome instability (4,15,20,27). Telomeric proteins stabilize the telomeres by protecting the single-stranded overhang from degradation or by remodeling the telomeres into a t-loop structure (5,6,15,23). Invasion of the single-stranded overhang into the doublestranded telomeric tract forms the t-loop structure. In vitro, t-loop assembly involves the binding of telomere repeat-binding factor 2 (TRF2), near the 3Ј telomeric overhang (48). A dominant-negative mutant of TRF2, TRF2⌬B⌬M , effectively strips TRF2 and its interacting factors off the telomeres and causes a loss of telomeric overhangs, apoptosis, senescence, and chromosome abn...

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