Prognostic biomarkers based on GUF1, EFTUD2 and GSPT1 targets affecting migration of gastric cancer cells.

Background: Eukaryotic elongation factor 1 alpha 2 (eEF1A2) is a protein coding gene which is involved in tumor development and progression in several types of human cancer, but little is known about the function of eEF1A2 proteins in gastric cancer (GC). This study aimed to investigate the effects of GUF1, EFTUD2 and GSPT1 on the migration of GC cells. Methods: The Oncomine and The Cancer Genome Atlas (TCGA) databases were used to evaluate the expression of GUF1, EFTUD2, GSPT1 and GSPT2 in GC and the association of eEF1A2 family with individual clinical characteristics. Kaplan-Meier (K-M) Plotter hinted the prognostic value of GUF1, EFTUD2, GSPT1 and GSPT2. GSE62254 and GSE66222 datasets were used to validate the expression of GUF1, EFTUD2, GSPT1. AGS cell line and GES line were also used for validating the function of GUF1, EFTUD2, GSPT1. RNA interference (RNAi) of GUF1, EFTUD2 and GSPT1 had been used to query those genes expression pattern and dissect the proliferation and migration in GC cell lines. Results: GUF1, EFTUD2 and GSPT1 were significantly up-regulated in GC cell lines. High expression of GUF1, EFTUD2 and GSPT1 was correlated with cell proliferation and migration induced in GC cells. GUF1, EFTUD2 and GSPT1 may be potential novel oncogenes that helps to maintain the survival of GC cells. Conclusions: This study identified that high levels of GUF1, EFTUD2 and GSPT1 expression are predictive biomarkers for a poor prognosis in GC.

Clinicopathological and surgical comparisons of differentiated thyroid cancer between China and the USA: A multicentered hospital-based study.

Background: Thyroid cancer (TC), was the fastest-rising tumor of all malignancies in the world and China, predominantly differentiated thyroid cancer (DTC). However, evidence on TC stage distribution and influencing factors of late-stage were limited in China. Methods: We carried out a retrospective study and enrolled TC patients who were first diagnosed and hospitalized in 8 hospitals in China in 2017. Logistic regression was used to evaluate associations between influencing factors and DTC stage. We extracted eligible primary DTC records newly diagnosed in 2017 from the USA's Surveillance, Epidemiology, and End Results (SEER) database. We compared clinicopathological features and surgical treatment between our DTC records and those from the SEER database. Results: A total of 1970 eligible patients were included, with 1861 DTC patients with known stage. Among patients ≥45 years old, males (OR = 1.76, 95%CI 1.17-2.65) and those with new rural cooperative medical scheme insurance (NCMS) (OR = 1.99, 95%CI 1.38-2.88) had higher risks of late-stage DTC (stage III-IV). Compared with SEER database, over-diagnosis is more common in China [more DTC patients with onset age< 45 years old (50.3 vs. 40.7%, P < 0.001), with early-stage (81.2 vs. 76.0%, P < 0.001), and with tumors<2cm (74.9 vs. 63.7%, P < 0.001)]. Compared with the USA, TC treatment is more conservative in China. The proportion of lobectomy in our database was significantly higher than that in the SEER database (41.3 vs. 17.0%, P < 0.001). Conclusions: Unique risk factors are found to be associated with late-stage DTC in China. The differences in the aspect of clinicopathological features and surgical approaches between China and the USA indicate that potential over-diagnosis and over-surgery exist, and disparities on surgery extent may need further consideration. The findings provided references for other countries with similar patterns.

LINC00665 affects the malignant biological behavior of ovarian cancer via the miR-148b-3p/KLF5.

This study investigated the expression and clinical significance of long intergenic noncoding RNA 00665 (LINC00665) in ovarian cancer (OC), as well as its effect on the malignant biological behavior of OC cells. The expression of LINC00665, miR-148b-3p, and Krüppel-like factor 5 (KLF5) in OC tissues and cells were determined by RT-qPCR. Western blot was used to detect the protein expression of KLF5. The expression patterns of LINC00665 in nuclear and cytoplasm fractions were undertaken using RT-qPCR. In addition, CCK-8 assay, clone formation assay, transwell, scratch test, and flow cytometry were respectively used to detect the cell activity, proliferation, invasiveness, healing of cells, and apoptosis rate of OC cells. Furthermore, the interactions between LINC00665 and miR-148b-3p and between miR-148b-3p and KLF5 were verified by the luciferase reporter assay, and the correlations among these three genes were analyzed. LINC00665 expression was upregulated both in OC cell lines and tissues. Si-LINC00665 inhibited cell proliferation, invasion, and migration and induced apoptosis to a certain extent. The subcellular fraction assay revealed LINC00665 to be located mainly in the cytoplasm. miR-148b-3p was a target of LINC00665, and KLF5 was directly targeted by miR-148b-3p. Si-LINC00665 inhibited KLF5 expression, miR-148b-3p inhibitor promoted KLF5 expression, and si-KLF5 inhibited LINC00665 expression. Interestingly, the expression of LINC00665 was reversely associated with miR-148b-3p expression but positively correlated with KLF5. Furthermore, miR-148b-3p expression was negatively correlated with KLF5. In addition, si-KLF5 inhibited the malignant biological behavior of OC cells, whereas miR-148b-3p inhibitor had the opposite effect. Most importantly, the si-LINC00665 could reverse the promotion effect of the miR-148b-3p inhibitor on the malignant biological behavior of OC cells. LINC00665 can be used as an effective prognostic indicator of OC, which has the potential to be a new therapeutic target.