Zebo Huang

Prognostic Value of PLR in Various Cancers: A Meta-Analysis

Background Recently, more and more studies investigated the association of inflammation parameters such as the Platelet Lymphocyte Ratio (PLR) and the prognosis of various cancers. However, the prognostic role of PLR in cancer remains controversial. Methods We conducted a meta-analysis of published studies to evaluate the prognostic value of PLR in various cancers. In order to investigate the association between PLR and overall survival (OS), the hazard ratio (HR) and its 95% confidence interval (CI) were calculated. Results A total of 13964 patients from 26 studies were included in the analysis. The summary results showed that elevated PLR was a negative predictor for OS with HR of 1.60 (95%CI: 1.35–1.90; Pheterogeneity <0.001). Subgroup analysis revealed that increased PLR was a negative prognostic marker in patients with gastric cancer (HR = 1.35, 95%CI: 0.80–2.25, Pheterogeneity = 0.011), colorectal cancer (HR = 1.65, 95%CI: 1.33–2.05, Pheterogeneity = 0.995), hepatocellular carcinoma (HR = 3.07, 95% CI: 2.04–4.62, Pheterogeneity = 0.133), ovarian cancer (HR = 1.57, 95%CI: 1.07–2.31, Pheterogeneity = 0.641) and non-small cell lung cancer (NSCLC) (HR = 1.85, 95% CI: 1.42–2.41, Pheterogeneity = 0.451) except for pancreatic cancer (HR = 1.00, 95%CI: 0.92–1.09, Pheterogeneity = 0.388). Conclusion The meta-analysis demonstrated that PLR could act as a significant biomarker in the prognosis of various cancers.

MiR-145, miR-133a and miR-133b inhibit proliferation, migration, invasion and cell cycle progression via targeting transcription factor Sp1 in gastric cancer

MicroRNAs have recently emerged as key regulators of gastric cancers. Here we found that miR‐145, miR‐133a and miR‐133b were down‐regulated in gastric cancer tissues and cell lines. Overexpression of miR‐145, miR‐133a and miR‐133b induced G1 cell cycle arrest and inhibited cell proliferation, migration and invasion in vitro. MiR‐145, miR‐133a and miR‐133b targeted the transcription factor SP1, knockdown of which reduced the expression of MMP‐9 and Cyclin D1 that were involved in cell growth and invasion. Thus, our findings demonstrated for the first time that miR‐145, miR‐133a and miR‐133b suppressed the proliferation, migration, invasion and cell cycle progression of gastric cancer cells through decreasing expression of Sp1 and its downstream proteins.

Diagnostic value of a plasma microRNA signature in gastric cancer: a microRNA expression analysis

The differential expression of microRNAs (miRNAs) in plasma of gastric cancer (GC) patients may serve as a diagnostic biomarker. A total of 33 miRNAs were identified through the initial screening phase (3 GC pools vs. 1 normal control (NC) pool) using quantitative reverse transcription polymerase chain reaction (qRT-PCR) based Exiqon panel (miRCURY-Ready-to-Use-PCR-Human-panel-I + II-V1.M). By qRT-PCR, these miRNAs were further assessed in training (30 GC VS. 30 NCs) and testing stages (71 GC VS. 61 NCs). We discovered a plasma miRNA signature including five up-regulated miRNAs (miR-185, miR-20a, miR-210, miR-25 and miR-92b), and this signature was evaluated to be a potential diagnostic marker of GC. The areas under the receiver operating characteristic curve of the signature were 0.86, 0.74 and 0.87 for the training, testing and the external validation stages (32 GC VS. 18 NCs), respectively. The five miRNAs were consistently dysregulated in GC tissues (n = 30). Moreover, miR-185 was decreased while miR-20a, miR-210 and miR-92b were increased in arterial plasma (n = 38). However, none of the miRNAs in the exosomes showed different expression between 10 GC patients and 10 NCs. In conclusion, we identified a five-miRNA signature in the peripheral plasma which could serve as a non-invasive biomarker in detection of GC.

miR-503 regulates the resistance of non-small cell lung cancer cells to cisplatin by targeting Bcl-2

Drug resistance is one of the leading causes of chemotherapy failure in cancer treatment. MicroRNAs (miRNAs or miRs) are short non-coding RNA molecules that post-transcriptionally regulate gene expression and play a critical role in diverse biological processes. In this study, we report that miR-503 regulates the resistance of non-small cell lung cancer cells to cisplatin. The expression of miR-503 was decreased in the cisplatin-resistant non-small cell lung cancer cells, A549/CDDP, compared with the parental A549 cells. The overexpression of miR-503 sensitized the A549/CDDP cells to cisplatin, whereas the inhibition of miR-503 in the A549 cells increased resistance to cisplatin. Mechanistically, miR-503 specifically targeted Bcl-2, an anti-apoptotic protein upregulated in the A549/CDDP cells. The ectopic expression of miR-503 reduced the Bcl-2 protein level and sensitized the A549/CDDP cells to cisplatin-induced apoptosis. Taken together, our results suggest that miR-503 regulates cell apoptosis, at least in part by targeting Bcl-2, and thus modulates the resistance of non-small cell lung cancer cells to cisplatin.

Prognostic Value of miR-21 in Various Cancers: An Updating Meta-Analysis

Background Recently, more and more studies investigated the value of microRNA (miRNA) as a diagnostic or prognostic biomarker in various cancers. MiR-21 was found dysregulated in almost all types of cancers. While the prognostic role of miR-21 in many cancers has been studied, the results were not consistent. Methods We performed a meta-analysis to investigate the correlation between miR-21 and survival of general cancers by calculating pooled hazard ratios (HR) and 95% confidence intervals (CI). Results The pooled results of 63 published studies showed that elevated miR-21 was a predictor for poor survival of general carcinomas, with pooled HR of 1.91 (95%CI: 1.66–2.19) for OS, 1.42 (95% CI: 1.16–1.74) for DFS and 2.2 (95% CI: 1.64–2.96) for RFS/CSS. MiR-21 was also a prognostic biomarker in the patients who received adjuvant therapy, with pooled HR of 2.4 (95%CI: 1.18–4.9) for OS. Conclusions Our results showed that miR-21 could act as a significant biomarker in the prognosis of various cancers. Further studies are warranted before the application of the useful biomarker in the clinical.

miR-135a/b Modulate Cisplatin Resistance of Human Lung Cancer Cell Line by Targeting MCL1

AbstractmicroRNAs (miRNAs) are short non-coding RNA molecules, which post-transcriptionally regulate genes expression and play crucial roles in diverse biological processes, such as development, differentiation, apoptosis, and proliferation. Here, we investigated the possible role of miRNAs in the development of drug resistance in human lung cancer cell line. We found that miR-135a/b were downregulated while MCL1 was upregulated in A549/CDDP (cisplatin) cells, compared with the parental A549 cells. In vitro drug sensitivity assay demonstrated that overexpression of miR-135a/b sensitized A549/CDDP cells to cisplatin. The luciferase activity of MCL1 3′-untranslated region-based reporter constructed in A549/CDDP cells suggested that MCL1 was the direct target gene of miR-135a/b. Enforced miR-135a/b expression reduced MCL1 protein level and sensitized A549/CDDP cells to CDDP-induced apoptosis. Taken together, our findings first suggested that hsa-miR-135a/b could play a role in the development of CDDP resistance in lung cancer cell line at least in part by modulation of apoptosis via targeting MCL1.

A six-microRNA panel in plasma was identified as a potential biomarker for lung adenocarcinoma diagnosis

Differently expressed microRNAs (miRNAs) in the plasma of lung adenocarcinoma (LA) patients might serve as biomarkers for LA detection. MiRNA expression profiling was performed using Exiqon panels followed by the verification (30 LA VS. 10 healthy controls (HCs)) with quantitative reverse transcription polymerase chain reaction (qRT-PCR) in the screening phase. Identified miRNAs were confirmed through training (42 LA VS. 32 HCs) and testing stages (66 LA VS. 62 HCs) by using qRT-PCR based absolute quantification methods. A total of six up-regulated plasma miRNAs (miR-19b-3p, miR-21-5p, miR-221-3p, miR-409-3p, miR-425-5p and miR-584-5p) were identified. The six-miRNA panel could discriminate LA patients from HCs with areas under the receiver operating characteristic curve of 0.72, 0.74 and 0.84 for the training, testing and the external validation stage (33 LA VS. 30 HCs), respectively. All the miRNAs identified except miR-584-5p were significantly up-regulated in LA tissues. MiR-19-3p, miR-21-5p, miR-409-3p and miR-425-5p showed high expression in arterial plasma with borderline significance. Additionally, miR-19-3p, miR-21-5p and miR-221-3p were significantly up-regulated in exosomes extracted from LA peripheral plasma samples. In conclusion, we identified a six-miRNA panel in peripheral plasma which might give assistance to the detection of LA at least for Asian population to a certain extent.

Clinical efficacy of mTOR inhibitors in solid tumors: a systematic review.

The common dysregulation of the mTOR signaling pathway in tumor cells makes it a key target in oncotherapy. To better understand the effects of mTOR inhibitors, we analyzed 32 published clinical trials on solid tumors other than renal cell cancer, neuroendocrine tumors and metastatic breast cancer, for mTOR inhibitors are already approved by the US FDA to treat the three cancers. A lack of therapeutic effects was observed when mTOR inhibitors were used as a single agent. When combined with other agents, mTOR inhibitors still lacked sufficient clinical activity or just had minimal activity. More studies are required to better understand the clinically effects of mTOR inhibitors and the development of novel mTOR inhibitors is absolutely necessary.

Efficacy of therapy with bortezomib in solid tumors: a review based on 32 clinical trials.

The ubiquitin-proteasome system is a major pathway for protein degradation, so that proteasome is now considered as an important target for drug discovery. Bortezomib, the first US FDA-approved proteasome inhibitor now used as a front-line treatment for multiple myeloma. To better understand the effects of bortezomib in cancer treatment, we carried out a review based on 32 published clinical trials to determine whether bortezomib will benefit patients with solid tumors. Information of complete response, partial response, stable disease and objective response rate was collected to assess clinical outcomes. A lack of therapeutic effects was observed when bortezomib was used as a single agent. Meanwhile, when bortezomib treatment was combined with other agents, bortezomib offered no statistically significant response versus these agents alone. High-quality studies are required to better understand the clinically effects of bortezomib and the development of a new generation of proteasome inhibitors is absolutely necessary.

A panel of microRNA signature in serum for colorectal cancer diagnosis

Dysregulated expression of specific microRNAs (miRNAs) in serum has been recognised as promising diagnostic biomarkers for colorectal cancer (CRC). In the initial screening phase, a total of 32 differentially expressed miRNAs were selected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) based Exiqon panel with 3 CRC pool samples and 1 normal control (NC) pool. Using qRT-PCR, selected serum miRNAs were further confirmed in training (30 CRC VS. 30 NCs) and testing stages (136 CRC VS. 90 NCs). We identified that serum levels of miR-19a-3p, miR-21-5p and miR-425-5p were significantly higher in patients with CRC than in NCs. The areas under the receiver operating characteristic (ROC) curve of the three-miRNA panel were 0.86, 0.74 and 0.87 for the training, testing and the external validation stages (30 CRC VS. 18 NCs), respectively. Significantly, elevated expression of the three miRNAs was also observed in CRC tissues (n = 24). Furthermore, the expression levels of the three miRNAs were significantly elevated in exosomes from CRC serum samples (n = 10). In conclusion, we identified a serum three-miRNA panel for the diagnosis of CRC.