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Tumor metastasis is a crucial impediment to the treatment of gastric cancer (GC), and the epithelial-to-mesenchymal transition (EMT) program plays a critical role for the initiation of GC metastasis. Thus, the aim of this study is to investigate the regulation of lnc-CTSLP4 in the EMT process during GC progression. We found that lnc-CTSLP4 was significantly downregulated in GC tumor tissues compared with adjacent non-tumor tissues, and its levels in GC tumor tissues were closely correlated with tumor local invasion, TNM stage, lymph node metastasis, and prognosis of GC patients. Loss-and gain-of-function assays indicated that lnc-CTSLP4 inhibited GC cell migration, invasion, and EMT in vitro, as well as peritoneal dissemination in vivo. Mechanistic analysis demonstrated that lnc-CTSLP4 could bind with Hsp90a/heterogeneous nuclear ribonucleoprotein AB (HNRNPAB) complex and recruit E3-ubiquitin ligase ZFP91 to induce the degradation of HNRNPAB, thus suppressing the transcriptional activation of Snail and ultimately reversing EMT of GC cells. Taken together, our results suggest that lnc-CTSLP4 is significantly downregulated in GC tumor tissues and inhibits metastatic potential of GC cells by attenuating HNRNPAB-dependent Snail transcription via interacting with Hsp90a and recruiting E3 ubiquitin ligase ZFP91, which shows that lnc-CTSLP4 could serve as a prognostic biomarker and therapeutic target for metastatic GC.

Background The Toronto hepatocellular carcinoma (HCC) risk index (THRI) was developed to predict HCC in patients with cirrhosis. This study aimed to validate the THRI in a 10-year Asian cohort. Methods A total of 2836 patients with cirrhosis at the First Affiliated Hospital of Soochow University between January 2008 and May 2018 were evaluated. Based on the THRI value at diagnosis, patients were divided into three groups (< 120, low-risk; 120–240, intermediate-risk; > 240, high-risk). Student’s t test and Fisher’s exact test were applied to compare parameters between the HCC group and the non-HCC group. The receiver operator characteristic (ROC) curve was drafted to identify the value of the THRI in predicting HCC. Logistic regression was utilized to assess the relationship between the development of HCC and THRI values. The incidence of HCC was calculated for the three groups using the Kaplan-Meier method, and curves were compared using the log-rank test. Results Of 520 patients enrolled in this study, 76 patients developed HCC. Patients who developed HCC had a higher THRI score than those who did not develop HCC (279.5 ± 57.1 vs. 232.3 ± 67.6, respectively, p < 0.001). The area under the ROC curve for the THRI to predict HCC was 0.707 ([95% CI 0.645–0.769], p < 0.001), with a sensitivity of 0.842 and a specificity of 0.486 when the cutoff THRI value was 226. Compared to the low-risk group, the high-risk group presented higher odds of developing HCC (adjusting odds ratio 1.026 [95% CI 1.002–1.051], p = 0.036). Differences existed in the cumulative incidence of HCC among the three risk groups (log-rank, p < 0.001). The 5-year cumulative HCC incidence of the low-risk group, intermediate-risk group, and high-risk group was 0%, 13%, and 34%, respectively. Conclusion This study validated THRI values for predicting HCC in Asians with cirrhosis, which presented a fine sensitivity to identify the high-risk population of HCC for secondary prevention. Electronic supplementary material The online version of this article (10.1186/s12957-019-1619-3) contains supplementary material, which is available to authorized users.