Comparison of the survival outcome of neoadjuvant therapy followed by radical surgery with that of concomitant chemoradiotherapy in patients with stage IB2-IIIB cervical adenocarcinoma.

PURPOSE: To compare the survival outcome of neoadjuvant therapy (NAT) (chemotherapy or chemotherapy and intracavitary brachytherapy (ICBT) followed by radical surgery and of concomitant chemotherapy and radiotherapy (CCRT) in patients with locally advanced cervical adenocarcinoma and identify predictors of cervical adenocarcinoma. METHODS: We retrospectively reviewed our medical records of cervical adenocarcinoma patients treated with either NAT + surgery or CCRT in our institution from January 2013 to December 2017. The patients were treated with two-dimensional radiotherapy or three-dimensional-conformal or intensity-modulated radiotherapy combined with intracavitary brachytherapy. The regimen of concomitant chemotherapy was weekly cisplatin. The neoadjuvant chemotherapy (NACT) was paclitaxel plus cisplatin. The primary end points were overall survival (OS) and progression-free survival (PFS). RESULTS: We enrolled 121 patients. There were 42 (34.7%) patients in the NAT + surgery group and 79 (65.3%) in the CCRT group. After univariate multivariate analysis, NAT was an independent predictor of OS (p = 0.008) and PFS (p = 0.006). After propensity score matching, the 5-year OS rates in the NAT + surgery and CCRT groups were 25% and 4%, respectively (p = 0.00014), and the 5-year PFS rates were 25% and 4%, respectively (p = 0.00015). Subgroup analysis showed that the 5-year OS and PFS rates in the NACT + surgery and CCRT groups were both 20% and 8%, respectively (p = 0.015). CONCLUSION: Compared with CCRT, NAT followed by radical surgery had better OS and PFS in locally advanced cervical adenocarcinoma. In subgroup analysis, OS and PFS were longer for NACT + surgery than for CCRT.

Overexpression LINC01082 suppresses the proliferation, migration and invasion of colon cancer.

Long non-coding RNAs (lncRNAs) are emerging as pivotal regulators in human cancer. LINC01082 was expressed as decreased in colon cancer by previous lncRNA-seq result and TCGA database, however, the role and function of LINC0182 is not clear in colon cancer. Here, we aimed to explore the role of LINC01082 in colon cancer for exploring the etiopathogenesis of colon cancer. RT-qPCR for LINC01082 expression in tissues (colon cancer vs. their matched adjacent non-cancerous tissues, ANT, n = 39) and cells (colon cancer cells vs. normal colon cells, n = 4) were performed. CCK-8 assay for proliferation of colon cancer, Transwell assay for migration and invasion were carried out in sw480 and sw620 cells. The results revealed that LINC01082 was significantly decreased in tissues and cell lines of colon cancer. Overexpressed LINC01082 significantly suppressed the proliferation ability of colon cancer cells. The migration and invasion of colon cancer cells were also suppressed after LINC01082 overexpression. These findings demonstrated that LINC01082 may act in suppressing the incidence and development of colon cancer via suppressing cell proliferation, migration and invasion, indicating that LINC01082 may act as a new tumor suppressor and may be a promising therapy target for colon cancer.

MiR-101-3p Regulates the Viability of Lung Squamous Carcinoma Cells via Targeting EZH2.

The aim of this study was to investigate the effects of miR-101-3p on the viability, migration, invasion, and mitosis of lung squamous carcinoma cells by inhibiting EZH2. In this study, RT-qPCR was used to detect the expression of miR-101-3p and EZH2 in both tissues and cells at RNA level. The dual luciferase reporter gene system was used to determine whether there was targeting relationship between miR-101-3p and EZH2-3'UTR. Western Blot was used to detect the expression of EZH2 as well as the proliferation and invasion related proteins. The CCK-8 assay, Transwell invasion assay, wound healing assay and flow cytometry were conducted to test the cell viability, invasion, migration and apoptosis. The results of RT-qPCR and Western blot showed that miR-101-3p was low-expressed and EZH2 was overexpressed in lung squamous cell carcinoma tissues and cells. Meanwhile the Western blot confirmed the effects of EZH2 expression on the proliferation and invasion of carcinoma cells. The results of luciferase assay and RT-qPCR showed that miR-101-3p had a negative regulation effect on EZH2. The CCK-8 assay, Transwell invasion assay, wound healing assay and flow cytometry results showed that the inhibition of EZH2 or the up-regulation of miR-101-3p inhibited the viability, migration, invasion and cell cycle but promoted cell apoptosis of lung squamous cell carcinoma. MiR-101-3p could inhibit the viability, migration, invasion, and cell cycle of lung squamous carcinoma cells by inhibiting the EZH2. J. Cell. Biochem. 118: 3142-3149, 2017. © 2016 Wiley Periodicals, Inc.

Genomic Landscape of Head and Neck Squamous Cell Carcinoma Across Different Anatomic Sites in Chinese Population.

BACKGROUND: The characteristics of head and neck squamous cell carcinoma (HNSCC) across different anatomic sites in the Chinese population have not been studied. To determine the genomic abnormalities underlying HNSCC across different anatomic sites, the alterations of selected cancer-related genes were evaluated. METHODS: Genomic DNA samples obtained from formalin-fixed, paraffin-embedded tissues were analyzed using targeted sequencing in a panel of 383 cancer-related genes to determine the genomic alterations. RESULTS: A total of 317 formalin-fixed, paraffin-embedded HNSCC specimens were collected, and a total of 2,156 protein-coding mutations, including 1,864 single nucleotide variants and 292 insertions and deletions, were identified across more than six different anatomic sites. Mutation loads were distinct across the anatomic sites. Larynx carcinoma was found with the highest mutation loads, whereas nasopharynx carcinoma showed the lowest mutation loads. A total of 1,110 gains and 775 losses were identified in the 317 specimens. Patients who had at least one clinically actionable alteration (levels 1-4 in OncoKB) were identified. One patient had an actionable alteration with level 1 evidence in OncoKB, TEX10-NTRK2 fusion, who may benefit from larotrectinib or entrectinib treatment. CONCLUSION: The genomic profiling of HNSCC using targeted sequencing can identify rational therapeutic candidate genes suitable for the treatment of the HNSCCs.

Loss of atypical chemokine receptor 4 facilitates C-C motif chemokine ligand 21-mediated tumor growth and invasion in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a common malignant disease that is prevalent in Asian countries. Atypical chemokine receptor 4 (ACKR4) binds to various chemokines, including C-C motif chemokine ligand (CCL)19, CCL21, CCL25 and C-X-C motif chemokine ligand 13, without inducing downstream signaling transduction. However, the role of ACKR4 in modulating NPC development remains unclear. In the present study, the effects of ACKR4 on NPC growth, invasion and metastasis were investigated, as well as the endogenous mechanisms through which ACKR4 mediates NPC development. The results demonstrated that ACKR4 was downregulated in human NPC tumor tissues, as compared with that in adjacent normal tissue. In a subcutaneous tumor animal model, the knockdown of ACKR4 enhanced NPC invasion and metastasis. Furthermore, CCL21 was accumulated in ACKR4 knockdown tumors. In vitro, the loss of ACKR4 increased CCL21-mediated SUNE-1 cell proliferation, epithelial-mesenchymal transition and invasion. In conclusion, the loss of ACKR4 promoted CCL21-mediated NPC development; thus, neutralizing CCL21 in NPC with low ACKR4 expression may be a novel treatment strategy.

Microarray Analysis of Circular RNA Expression Profile Associated with 5-Fluorouracil-Based Chemoradiation Resistance in Colorectal Cancer Cells.

Preoperative 5-fluorouracil- (5-FU-) based chemoradiotherapy is a standard treatment for locally advanced colorectal cancer (CRC). However, the effect of 5-FU-based chemoradiotherapy on CRC is limited due to the development of chemoradiation resistance (CRR), and the molecular mechanisms underlying this resistance are yet to be investigated. Recently, circular RNAs (circRNAs), which can function as microRNA sponges, were found to be involved in the development of several cancers. In this study, we focused on clarifying the modulation of the expression profiles of circRNAs in CRR. Microarray analysis identified 71 circRNAs differentially expressed in chemoradiation-resistant CRC cells. Among them, 47 were upregulated and 24 were downregulated by more than twofold. Furthermore, expression modulation of five representative circRNAs was validated by quantitative reverse transcription PCR (qRT-PCR). Moreover, these modulated circRNAs were predicted to interact with 355 miRNAs. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the most modulated circRNAs regulate several cancers and cancer-related pathways, and the possible mechanism underlying CRR was discussed. This is the first report revealing the circRNA modulations in 5-FU chemoradiation-resistant CRC cells by microarray. The study provided a useful database for further understanding CRR and presents potential targets to overcome CRR in CRC.

Microarray Analysis of Long Non-coding RNA Expression Profile Associated with 5-Fluorouracil-Based Chemoradiation Resistance in Colorectal Cancer Cells.

BACKGROUND: Preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy is a standard treatment for locally advanced colorectal cancer (CRC). However, CRC cells often develop chemoradiation resistance (CRR). Recent studies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processes and human diseases, as well as chemotherapy resistance. Since the roles of lncRNAs in 5-FU-based CRR in human CRC cells remain unknown, they were investigated in this study. MATERIALS AND METHODS: A 5-FU-based concurrent CRR cell model was established using human CRC cell line HCT116. Microarray expression profiling of lncRNAs and mRNAs was undertaken in parental HCT116 and 5-FU-based CRR cell lines. RESULTS: In total, 2,662 differentially expressed lncRNAs and 2,398 mRNAs were identified in 5-FU-based CRR HCT116 cells when compared with those in parental HCT116. Moreover, 6 lncRNAs and 6 mRNAs found to be differentially expressed were validated by quantitative real time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated involvement of many, such as Jak- STAT, PI3K-Akt and NF-kappa B signaling pathways. To better understand the molecular basis of 5-FU-based CRR in CRC cells, correlated expression networks were constructed based on 8 intergenic lncRNAs and their nearby coding genes. CONCLUSIONS: Changes in lncRNA expression are involved in 5-FU-based CRR in CRC cells. These findings may provide novel insight for the prognosis and prediction of response to therapy in CRC patients.