Hepatocellular carcinoma (HCC) is a serious threat to human health. HCC is a malignant tumor and its invasion and metastasis are the result of multigene interactions. Matrix metalloproteinase-2 (MMP-2) is capable of degrading the majority of components of the extracellular matrix and is regarded to closely correlate with tumor invasion and metastasis. Furthermore, the hypoxia-inducible factor 1α (HIF-1α) is an important transcription factor, which is closely associated with the process of tumor growth. The aim of the present study was to investigate the expression of MMP2 and HIF-1α) in HCC, and the relationship between MMP2/HIF-1α protein expression and the clinical/pathological characteristics of HCC. The mRNA levels of MMP2 and HIF-1α were detected in 32 cases of HCC and the corresponding normal adjacent tissues with fluorescence-based quantitative polymerase chain reaction (qPCR). The protein expression of MMP2 and HIF-1α was assessed in 45 HCC cases and 33 cases of corresponding normal adjacent tissue, using immunohistochemical methods. The association between MMP2/HIF-1α and pathological features of HCC, and the correlation between MMP2 and HIF-1α were analyzed. The Kaplan-Meier method was used to assess the impact of MMP2 and HIF-1α expression on survival. The fluorescence-based qPCR demonstrated that MMP2 and HIF-1α mRNA expression levels in the HCC tissues were 0.84±0.17 and 0.87±0.11, respectively, which were significantly higher than those in the adjacent normal tissues (0.70±0.13 and 0.68±0.13, respectively; P<0.05). Immunohistochemical analysis revealed that MMP2 and HIF-1α protein expression in the HCC tissues was 63.1 and 70.8%, respectively, which was also higher than that in the adjacent normal tissues (34.2 and 36.8%, respectively). There was no significant correlation between the expression of MMP2 or HIF-1α protein and the age or gender of patients with HCC (P>0.05). However, there was significant correlation between MMP2 or HIF-1α protein expression and tumor size, metastasis, presence of a capsule and clinical TNM staging of HCC. Their expression also had a significant effect on patient survival time. In conclusion, MMP2 and HIF-1α are overexpressed in HCC, and the MMP2 signaling pathway may promote the development of HCC together with HIF-1α.

Background: A series of studies have explored the prognostic value of programmed death-ligand 1 (PD-L1) in patients with endometrial cancer (EC); however, the results are controversial. Therefore, this meta-analysis was performed to estimate the associations between PD-L1 expression and the prognosis and clinicopathological features of EC. Methods: A comprehensive literature search of PubMed, Web of Science, and Embase was conducted up until September 06, 2019. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) were computed using the random-effects model (REM) or fixed-effects model (FEM). Odds ratios (ORs) and 95% CIs were calculated to evaluate the relationship between PD-L1 and clinicopathological factors. Results: A total of 9 studies with 1,615 patients were included in the meta-analysis. The combined data showed that high expression of PD-L1 was not significantly correlated with OS (HR = 1.20, 95% CI = 0.41-3.52, p = 0.737) or PFS (HR = 1.12, 95% CI = 0.50-2.54, p = 0.778) in EC. In addition, PD-L1 expression was significantly associated with poor differentiation (OR = 2.82, 95% CI = 1.96-4.06, P < 0.001) and advanced stage (OR = 1.71, 95% CI = 1.12-2.60, p = 0.013). Conclusion: This meta-analysis suggests that PD-L1 expression is not associated with poor prognosis in patients with EC. However, PD-L1 expression is positively correlated with poor differentiation and advanced tumor stage in EC.

Chemotherapeutic drug resistance is correlated with treatment failure and poor prognosis among lung cancer patients. Numerous studies indicate the relevance of miRNAs in inducing certain drug resistance. In the course of the study, we unexpectedly found that miR-144-3p could regulate the cisplatin resistance of lung cancer cells via Nrf2. However, Nrf2 also could reverse activate the expression of miR-144-3p by binding to the ARE box in the miR-144-3p promoter. This may be a self-protection mechanism of the body. In addition, we also found that in other cancer cell lines, such as HepG2, miR-144-3p also had the function of regulating cisplatin resistance. These findings may provide some theoretical reference for the clinical inhibition of cisplatin resistance.

Background Serine/threonine protein kinase 25 (STK25) plays an important role in regulating glucose and insulin homeostasis and in ectopic lipid accumulation. It directly affects the progression and prognosis of nonalcoholic fatty liver disease (NAFLD). However, the effects of STK25 on lipid metabolism in hepatocellular carcinoma (HCC) remain unexplored. The aim of this study was to investigate the role of STK25 in HCC and to elucidate the underlying mechanisms. Methods Immunohistochemistry was used to measure the expression of STK25 in hepatic tissues of HCC patients, and public datasets were used as supplementary material for predicting the expression of STK25 and the prognosis of patients with HCC. The interaction between STK25 and striatin (STRN) was determined by the STRING database, immunohistochemistry and western blot analyses. The involved signaling pathway was detected by the KEGG database and western blot. Moreover, the biological behaviors of the HCC cells were detected by wound healing assays, Transwell invasion assays and oil red O staining. Finally, it was verified again by xenograft model. Results STK25 is highly expressed in HCC patients and is associated with poor prognosis. STK25 knockdown inhibited the HCC cell invasion and proliferation, promotes apoptosis. Consistently, STK25 knockdown inhibited tumor growth in xenograft mouse model. Besides, STK25 deficiency decreased lipid synthesis, energy reserve, epithelial-mesenchymal transition (EMT) by down-regulating lipid metabolism signaling pathway. STRN could reverse the change of lipid metabolism. Conclusions Our results demonstrated that STK25 interacted with STRN to regulates the energy reserve and EMT via lipid metabolism reprogramming. Accordingly, high expression of STK25 may be associated with HCC patients and poor prognosis, which implicates STK25 could be a potential target for lipid metabolism in cancer therapy.

Background: Universal gene targets are in persistent demand by real-time quantitative polymerase chain reaction (RT-qPCR)-based methods in acute leukemia (AL) diagnosis and monitoring. Human Krüppel-like factor 3 (hKLF3), a newly cloned human transcription factor, has proved to be a regulator of hematopoiesis. Methods: Sanger sequencing was performed in bone marrow (BM) samples from 17 AL patients for mutations in hKLF3 coding exons. hKLF3 expression in peripheral blood (PB) and BM samples from 45 AL patients was dynamically detected by RT-qPCR. PB samples from 31 healthy donors were tested as normal controls. Results: No mutation was sequenced in hKLF3 coding exons. hKLF3 expression in PB of AL was significantly lower than that in healthy donors [0.30 (0.02-1.07) vs 1.18 (0.62-3.37), P < .0001]. Primary acute myeloid leukemia (AML) exhibited the least expression values compared with secondary AML and acute lymphoblastic leukemia. Receiver operating characteristic (ROC) analyses suggested that hKLF3expression in PB was a good marker for AML diagnosis with an AUC of 0.99 (95% CI 0.98-1.00) and an optimum cutoff value of 0.67 (sensitivity 93.94% and specificity 93.55%). hKLF3 expression was upregulated significantly when AML patients acquired morphological complete remission (CR), and the level of hKLF3 seemed to be higher in patients with deeper CR than in patients with minimal residual disease (MRD). Paired PB and BM samples showed highly consistent alteration in hKLF3 expression (r = .6533, P = .001). Besides, a significantly converse correlation between decreased hKLF3 expression in PB and markers for leukemic load was observed. Conclusions: hKLF3 expression in PB may act as a potential marker for AL diagnosis and monitoring. K E Y W O R D Sacute leukemia, biomarker, diagnosis, human krüppel-like factor 3, minimal residual disease 2804 | YAN et Al.