Huntingtin-associated protein 1 is a potential tumor suppressor for gastric cancer.

BACKGROUND: Gastric cancer is heterogeneous cancer and the causes of this disease are complex. New diagnostic and therapeutic targets are urgently needed to explore. Huntingtin-associated protein 1 (HAP1) is directly related to Huntington's disease (HD). However, patients with Huntington's disease have a lower incidence of cancer. Therefore, we are committed to studying the correlation between HAP1 and gastric carcinogenesis and development. METHODS AND RESULTS: Immunohistochemical staining, western blot analysis, and RT-qPCR were conducted to explore the localization and expression of HAP1 in gastric cancer. To study the biological significance of HAP1, we overexpressed HAP1 in both MKN28 and AGS cell lines by lentivirus infection. To explore the role of HAP1 in cell proliferation, the cells counting assay, EdU incorporation assay, and colony formation assay were carried out. We performed the wound healing assay and transwell assay to study the cell migration and invasion. To further investigate whether HAP1 could regulate gastric cancer cell death during glucose deprivation, Annexin V-FITC/PI staining was performed. In our study, we elucidated that HAP1 was downregulated in gastric cancer. What's more, overexpressing HAP1 inhibited cell proliferation, cell migration and invasion, and triggered apoptosis during glucose deprivation. More importantly, the antitumor properties and mechanisms of HAP1 have been elucidated further in gastric cancer. CONCLUSIONS: Taken together, the available evidence implies that HAP1 may serve as a potential tumor suppressor, making it a significant target in preventing and treating gastric cancer. This research provides a theoretical basis for the early diagnosis, clinical targeted therapy, and prognosis evaluation of gastric cancer.

Diagnostic value of alpha-fetoprotein-L3 and Golgi protein 73 in hepatocellular carcinomas with low AFP levels.

This study aimed to investigate the clinical values of serum alpha-fetoprotein-L3 (AFP-L3) and Golgi protein 73 (GP73) in the diagnosis of hepatocellular carcinoma (HCC) with low alpha-fetoprotein (AFP). From January 2011 to December 2013, 50 low-AFP HCC patients confirmed by the color Doppler flow imaging (CDFI) and pathological examinations were collected. Forty-five patients with chronic liver diseases were also selected, including 29 liver cirrhosis patients, 15 chronic hepatitis B patients, and one severe hepatitis patient. Furthermore, 100 health volunteers with no evidence of benign or malignant liver diseases were included. The enzyme-linked immunosorbent assay (ELISA) method was applied to the GP73 quantitative assay. Serum AFP concentrations were determined using immunoassays utilizing enhanced chemiluminescence. Diagnostic accuracy of GP73 and AFP-L3 assays for low-AFP HCC was evaluated using receiver operating characteristic (ROC) curve analysis. Statistical analyses were conducted with the GraphPad Prism 5.0 software. Low-AFP HCC patients (35/50) exhibited higher positive rates of AFP-L3 than non-HCC patients (5/45) and healthy controls (2/100) (both P < 0.05). There were also significant differences in the positive rate of GP73 of low-AFP HCC patients (40/50) compared to those of non-HCC patients (3/45) and healthy controls (1/100) (both P < 0.05). However, no obvious differences in the positive rates of AFP-L3 and GP73 were observed between non-HCC patients and healthy controls (both P > 0.05). ROC curves showed that the area under the curve (AUC) of AFP-L3 for the diagnosis of low-AFP HCC was 0.6994 (sensitivity [Sen] = 70.0 %, specificity [Spe] = 95.2 %, accuracy = 88.7 %), while the AUC of GP73 was 0.8411 (Sen = 80.0 %, Spe = 97.2 %, accuracy = 92.8 %). Compared with single detection, the combination of AFP-L3 and GP73 levels for the diagnosis of low-AFP HCC showed higher Sen (94.0 %), Spe (93.1 %), and better accuracy (93.3 %). Our findings provide empirical evidence that the combination of AFP-L3 and GP73 is a good diagnostic strategy for low-AFP HCC.