The role of cytoskeleton-associated membrane protein 4 (CKAP4) in hepatocellular carcinoma (HCC) is controversial. The present study aimed to investigate the association between tumor CKAP4 mRNA expression and clinicopathological characteristics and prognosis in patients with HCC. Data relating to CKAP4 mRNA expression in HCC tumor and normal adjacent liver tissues, and clinicopathological characteristics, were downloaded from the Gene Expression Omnibus and The Cancer Genome Atlas databases. The CKAP4 mRNA levels in tumor tissues were compared with those in normal adjacent liver tissues, their association with clinicopathological parameters was analyzed, and diagnostic and prognostic values were evaluated in patients with HCC. In all 4 datasets (total samples, n=693), CKAP4 mRNA levels were significantly higher in tumor tissues compared with adjacent tissues (all P<0.001), with the area under the receiver operating characteristic curve ranging from 0.799-0.898 for HCC diagnosis. In patients with HCC with available clinical data (n=361), the low-level CKAP4 mRNA group exhibited a lower body mass index (P=0.005), higher α-fetoprotein level (P<0.001), more frequent adjacent liver tissue inflammation (P<0.001), poorer tumor histological grade (P<0.001), higher Ishak fibrosis score (P= 0.035) and a more advanced tumor node metastasis (TNM) stage (P=0.014) compared with the high-level CKAP4 mRNA group. Patients stratified by all the above parameters, except for TNM stage, exhibited significantly different expression of tissue CKAP4 mRNA (P<0.05-0.001). Furthermore, higher CKAP4 mRNA levels were observed in patients who died within one year following diagnosis compared with those who survived >3 years (P=0.003). The high-level CKAP4 mRNA group also exhibited lower overall survival (OS) and disease-free survival (DFS) rates compared with the low-level group [hazard ratio (HR)=1.494; 95% confidence interval (CI), 1.044-2.138; P=0.028] for OS and (HR=1.616; 95% CI, 1.022-2.555; P=0.040) for DFS. The results of the present study suggest that CKAP4 mRNA is upregulated in HCC tumor tissues compared with normal adjacent tissues, and is associated with poor clinical prognosis, pathological features and survival in patients with HCC. Thus, CKAP4 is a potential biomarker for HCC diagnosis and prognosis.

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Two new chlorinated metabolites, 8-chlorine-5-hydroxy-2,3-dimethyl-7-methoxychromone (1) and 3,4-dichloro-1H-pyrrole-2,5-dione (3), and eight known compounds (2 and 4–9) were isolated from the mangrove sediments-derived fungus Mollisia sp. SCSIO41409. Their structures were elucidated by physicochemical properties and extensive spectroscopic analysis. The absolute configuration of stemphone C (4) was established for the first time by the X-ray crystallographic analysis. Compounds 3 and 4 showed different intensity of antimicrobial activities against several pathogenic fungi and bacteria, and antiproliferative activities against two human prostate cancer cell lines (IC50 values 2.77 to 9.60 μM). Further, stemphone C (4) showed a reducing PC-3 cell colony formation, inducing apoptosis and blocking the cell cycle at S-phase in a dose-dependent manner; thus, it could be considered as a potential antiproliferative agent and a promising anti-prostate cancer lead compound.

Supplemental Table S1. The differentially expressed genes between tumor and adjacent liver tissues in patients with hepatocellular carcinoma Upregulated genes Downregulated genes

Prostate cancer is a common cancer in elderly males. Significant progress has been made in the drug therapies for prostate cancer in recent years. However, side effects are still problems that have not been overcome by the currently used anti-prostate cancer drugs. Novel technologies can be applied to reduce or even eliminate the side effects of drugs. An aptamer may be a sequence of nucleic acids or peptides that can specifically recognize proteins or cells. Taking advantage of this feature, scientists have designed aptamer–drug delivery systems for the development of anti-prostate cancer agents. Theoretically, these aptamer–drug delivery systems can specifically recognize prostate cancer cells and then induce cell death without attacking normal cells. We collected the relevant literature in this field and found that at least nine compounds have been prepared as aptamer–drug delivery systems to evaluate their precise anti-prostate cancer effects. However, the currently studied aptamer–drug delivery systems have not yet entered the market due to defects. Here, we analyze the published data, summarize the characteristics of these delivery systems, and propose ways to promote their application, thus promoting the development of the aptamer–drug delivery systems against prostate cancer.

Death receptor 5 (DR5) is a membrane protein that mediates exogenous apoptosis. Based on its function, it is considered to be a target for the treatment of cancers including prostate cancer. It is encouraging to note that a number of drugs targeting DR5 are now progressing to different stages of clinical trial studies. We collected 38 active compounds that could produce anti-prostate-cancer effects by modulating DR5, 28 of which were natural compounds and 10 of which were synthetic compounds. In addition, 6 clinically used chemotherapeutic agents have also been shown to promote DR5 expression and thus exert apoptosis-inducing effects in prostate cancer cells. These compounds promote the expression of DR5, thereby enhancing its function in inducing apoptosis. When these compounds were used in combination with the natural ligand of DR5, the number of apoptotic cells was significantly increased. These compounds are all promising for development as anti-prostate-cancer drugs, while most of these compounds are currently being evaluated for their anti-prostate-cancer effects at the cellular level and in animal studies. A great deal of more in-depth research is needed to evaluate whether they can be developed as drugs. We collected literature reports on small molecules against prostate cancer through modulation of DR5 to understand the current dynamics in this field and to evaluate the prospects of small molecules against prostate cancer through modulation of DR5.

Advanced prostate cancer has a poor prognosis, and it is urgent to develop new effective drugs. 5′-Epiequisetin is a tetramic acid derivative which was isolated from a marine sponge-derived fungus Fusarium equiseti in our previous study. In this study, 5′-epiequisetin showed cytotoxicity against four prostate cancer cell lines, namely, LNCaP, 22Rv1, DU145, and PC-3 cells, with the lowest IC50 value of 4.43 ± 0.24 μM in PC-3 cells. Further studies showed that it could dramatically regulate the clonal colony formation, apoptosis, and migration of PC-3 cells. In addition, flow cytometry data showed that 5′-epiequisetin could block the cell cycle at the G1 phase. Proteome profiler array and Western blot revealed that 5′-epiequisetin could regulate the expression of proteins responsible for cell proliferation, apoptosis, and migration. 5′-Epiequisetin regulated the expression of PI3K, Akt, phosphorylated Akt, and proteins which control the cell cycle. Meanwhile, 5′-epiequisetin upregulated expression of DR5 and cleave-caspase 3, which play important roles in the process of apoptosis. Moreover, when DR5 was silenced by small interfering RNA, the proportion of apoptotic cells induced by 5′-epiequisetin remarkably declined. In addition, 5′-epiequisetin downregulated the expression of survivin which plays a key role in the process of survival and apoptosis. 5′-Epiequisetin also impacted beta-catenin and cadherins, which were associated with cell migration. In addition, 5′-Epiequisetin significantly inhibited the progression of prostate cancer in mice, accompanied by regulating the protein expression of DR5, caspase 8, survivin, and cadherins in vivo. Taken together, these findings indicated that 5′-epiequisetin showed an anti–prostate cancer effect by inducing apoptosis and inhibiting cell proliferation and migration both in vitro and in vivo, suggesting a promising lead compound for the pharmacotherapy of prostate cancer.

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