Interaction Between Macrophage Extracellular Traps and Colon Cancer Cells Promotes Colon Cancer Invasion and Correlates With Unfavorable Prognosis.

Background: Macrophage extracellular traps (METs) and tumor-infiltrating macrophages contribute to the progression of several diseases. But the role of METs and tumor-infiltrating macrophages in colon cancer (CC) has not been illuminated. In this study, we aimed to clarify the prognostic value of METs for CC patients and to explore the interaction between CC cells and METs in vitro and in vivo. Methods: A training cohort consisting of 116 patients and a validation cohort of 94 patients were enrolled in this study. Immunofluorescence (IF) staining was conducted to determine METs formation in CC patients. Cox regression was used to perform prognostic analysis and screen out the best prognostic model. A nomogram was established to predict 5-year overall survival (OS). The correlation between METs with clinicopathological features and inflammatory markers was analyzed. The formation of METs in vitro was detected by SYTOX® green and IF staining, and the effect of METs on CC cells was detected by transwell assays. PAD2-IN-1, a selective inhibitor of peptidylarginine deiminase 2 (PAD2), was introduced to destroy the crosstalk between CC cells and METs in vitro and in vivo. Results: METs levels were higher in CC tissues and were an independent prognostic factor for CC patients. The prognostic model consisting of age, tumors local invasion, lymph node metastasis and METs were confirmed to be consistent and accurate for predicting the 5-year OS of CC patients. Besides, METs were correlated with distant metastasis and inflammation. Through in vitro experiments, we confirmed that there was a positive feedback loop between CC cells and METs, in that METs promoted the invasion of CC cells and CC cells enhanced the production of METs, in turn. This interaction could be blocked by PAD2-IN-1 inhibitors. More importantly, animal experiments revealed that PAD2-IN-1 inhibited METs formation and CC liver metastasis in vivo. Conclusions: METs were the potential biomarker of CC patient prognosis. PAD2-IN-1 inhibited the crosstalk between CC cells and METs in vitro and in vivo, which should be emphasized in CC therapy.

LncRNA TTN­AS1 promotes endometrial cancer by sponging miR­376a­3p.

Increasing research has demonstrated that lncRNAs participate in the development of multiple cancer types. However, the role of TTN­AS1 in endometrial cancer (EC) remains unknown. The present study aimed to explore the function of titin­antisense RNA1 (TTN­AS1) in EC progression and the underlying mechanisms. qRT­PCR was performed to assess the TTN­AS1 expression patterns in EC tissues and cell lines. Loss of function experiments were carried out to estimate the effects of TTN­AS1 on EC cell proliferation, migration and invasion. To reveal the underlying mechanisms, informatics tools were used to predict the targets. Rescue experiments were performed to investigate the TTN­AS1­regulated miR­376a­3p/pumilio homolog 2 (PUM2) axis involved. The results of the present study revealed that TTN­AS1 was highly expressed in both EC tissues and cell lines, and TTN­AS1 knockdown inhibited EC cell proliferation, migration and invasion. With respect to the mechanisms, miR­376a­3p was revealed to be targeted by TTN­AS1, and reversed the effects on EC development induced by TTN­AS1. In addition, PUM2 was positively regulated by TTN­AS1, and miR­376a­3p mediated the regulation between them. Furtherly, in vivo experiments confirmed the results. Collectively, TTN­AS1 enhanced EC cell proliferation and metastasis by targeting the miR­376a­3p/PUM2 axis, which may shed light on EC diagnosis and treatment.

Whole-exome and RNA sequencing reveal novel insights into the pathogenesis of HPV associated cervical cancer.

BACKGROUND: Worldwide, cervical cancer is the fouth leading cause of deaths in gynecological oncology. Although the causes of cervical cancer have been extensively investigated, understanding of its exact pathogenesis remains incomplete. OBJECTIVE: This study aimed to identify alterations of genome and transcriptome of HPV associated cervical cancer pathogenesis using multi-omics approaches. METHODS: Cervical cancer and matched adjacent non-tumor specimens of one HPV16+ and two HPV- patients were sampled for whole-exome sequencing (WES) and RNA sequencing to characterize DNA mutations and gene expression profiles. WES and Affymetrix SNP 6.0 arrays data were analyzed from 6 HPV- and 93 HPV16+ cervical cancer patients in the cancer genome atlas (TCGA) database, as an independent validation group. RESULTS: WES identified 64 somatic mutation genes in tumors of 3 patients. HPV16+ tumor got fewer somatic mutated genes than HPV- tumors, which was validated by TCGA results. In this study, somatic mutated profile, CNV and gene expression heat map presented that HPV16+ tumors was distinct with HPV- tumors. The most significant altered pathways and GO terms were both related with cell cycle. Integrated analysis of multi-omics showed positive correlation between gene expression level and copy numbers. CONCLUSIONS: The results of this study provided novel insights into the pathogenesis of HPV associated cervical cancer.

Risk Factors of Regional Lymph Node Metastasis in Patients with Cervical Cancer.

OBJECTIVES: To explore the risk factors related to regional lymph node metastasis in cervical cancer and analyze the value of independent risk factors in predicting regional lymph node metastasis. METHODS: We retrospectively analyzed the clinical data of 699 patients who underwent surgery for stage IB1-IIA2 cervical cancer in Quanzhou First Hospital affiliated to Fujian Medical University from 2010 to 2016. The patients were divided into metastasis (n = 92) and non-metastasis (n = 607) groups based on the postoperative pathology of regional lymph node status. The relevant clinicopathological features of the metastasis and non-metastasis groups were compared through variance analysis and chi-square tests. Logistic regression was adopted to screen relevant independent risk factors of regional lymph node metastasis. RESULTS: In univariate analysis, International Federation of Gynecology and Obstetrics (FIGO) stages, serum squamous cell carcinoma antigen (SCC-Ag), histological type of squamous carcinoma and maximal tumor diameter were related factors for lymphatic metastasis in patients with cervical cancer. In multivariate analysis, SCC-Ag and histological type of squamous carcinoma were independent prognostic factors for lymphatic metastasis in patients with cervical cancer. Pre-treatment SCC-Ag serum levels, as a predictor of lymph node metastasis of cervical cancer, revealed a sensitivity of 62.07% (95% confidence interval (CI): 51.03-72.62%), specificity of 65.15% (59.07-70.89%), and area under the receiver operating characteristic (ROC) curve of 0.69 (95% CI: 0.61-0.76). CONCLUSIONS: Cervical cancer patients whose pathological type is squamous carcinoma with high levels of SSC-Ag pre-operation are more likely to be diagnosed with regional lymph node metastasis. Standardized lymph node dissection should be implemented during operation.