DataSheet_1_First-Trimester Serum Cytokine Profile in Pregnancies Conceived After Assisted Reproductive Technology (ART) With Subsequent Pregnancy-Induced Hypertension.docx

Pregnancy-induced hypertension (PIH) is one of the most common pregnancy complications that seriously affects the mother and fetus. The incidence of PIH is higher in pregnancies conceived after assisted reproductive technology (ART) than in spontaneous pregnancies; thus, exploring potential serum biomarkers before PIH onset is of great significance for effective early prediction and prevention of PIH in the ART population. Cytokines are involved in the inflammatory response and immune regulation, which play an essential role in the pathogenesis of PIH. A description of the cytokine profile in the first trimester of pregnancy could help identify new diagnostic tools and develop targeted therapies for PIH in the ART population. The concentrations of classical predictive markers for PIH and another 48 cytokines were measured in the first-trimester pregnancy serum samples from 33 PIH patients and 33 matched normotensive controls (NC), both of whom conceived after ART treatment. The measured values were compared and analyzed between NC and PIH, followed by comprehensive bioinformatic analysis and logistic regression analysis. There was no significant difference in classical predictive markers, including Activin A, PlGF, sFLT1 (VEGFR), and sFLT1/PlGF, between the PIH and NC groups (P > 0.05), while 29 cytokines were significantly lower in the PIH group than in the NC group (P < 0.05). Logistic regression analysis revealed that 17 cytokines (IL-2Rα, M-CSF, IL-6, IL-2, β-NGF, IL-7, IL-12 (p70), SCF, IL-10, IL-9, MIG, GM-CSF, LIF, IL-1α, MCP-3, IL-4, and HGF) in the first-trimester pregnancy serum were significantly negatively correlated with the subsequent onset of PIH. With the top 3 cytokines (IL-7, MIG, and SCF) of receiver operating characteristic (ROC) analysis, we constructed an efficient multifactor combined detection and prediction model for PIH in ART pregnancy. Classical early predictors for hypertensive disorder complicating pregnancy cannot distinguish PIH from their normal peers in ART pregnancy. In comparison, the description of the cytokine profile in the first trimester of pregnancy enables us to distinguish high-risk ART pregnancy for PIH, permitting enough time for PIH prevention therapy. The cytokine profile we described also provides immunological insight into the further mechanistic exploration of PIH.</p

Image6_ELK1 Enhances Pancreatic Cancer Progression Via LGMN and Correlates with Poor Prognosis.PNG

Pancreatic cancer is one of the most lethal cancers and its prognosis is extremely poor. Clarification of molecular mechanisms and identification of prognostic biomarkers are urgently needed. Though we previously found that LGMN was involved in pancreatic carcinoma progression, the upstream regulation of LGMN remains unknown. We used reliable software to search for the potential transcription factors that may be related with LGMN transcription, we found that ELK1 could be a new regulator of LGMN transcription that binded directly to the LGMN promoter. Moreover, knocking down of ELK1 reduced pancreatic cancer cells proliferation, invasion and survival, while LGMN restored the malignancy of pancreatic cancer in vitro and in vivo. Overexpression of ELK1 further increased cancer cells proliferation, invasion and survival. Clinically, ELK1 and LGMN were positively correlated with clinical stage, degree of differentiation and Lymph node infiltration. ELK1 and LGMN were identified as independent prognostic factors for overall survival. The patients with low expression of ELK1/LGMN survived an average of 29.65 months, whereas those with high expression of ELK1/LGMN survived an average of 16.67 months. In conclusive, our results revealed a new mechanism by which ELK1 promoted the progression of pancreatic cancer via LGMN and conferred poor prognosis.</p

Table3_ELK1 Enhances Pancreatic Cancer Progression Via LGMN and Correlates with Poor Prognosis.DOCX

Pancreatic cancer is one of the most lethal cancers and its prognosis is extremely poor. Clarification of molecular mechanisms and identification of prognostic biomarkers are urgently needed. Though we previously found that LGMN was involved in pancreatic carcinoma progression, the upstream regulation of LGMN remains unknown. We used reliable software to search for the potential transcription factors that may be related with LGMN transcription, we found that ELK1 could be a new regulator of LGMN transcription that binded directly to the LGMN promoter. Moreover, knocking down of ELK1 reduced pancreatic cancer cells proliferation, invasion and survival, while LGMN restored the malignancy of pancreatic cancer in vitro and in vivo. Overexpression of ELK1 further increased cancer cells proliferation, invasion and survival. Clinically, ELK1 and LGMN were positively correlated with clinical stage, degree of differentiation and Lymph node infiltration. ELK1 and LGMN were identified as independent prognostic factors for overall survival. The patients with low expression of ELK1/LGMN survived an average of 29.65 months, whereas those with high expression of ELK1/LGMN survived an average of 16.67 months. In conclusive, our results revealed a new mechanism by which ELK1 promoted the progression of pancreatic cancer via LGMN and conferred poor prognosis.</p

Table1_ELK1 Enhances Pancreatic Cancer Progression Via LGMN and Correlates with Poor Prognosis.DOC

Pancreatic cancer is one of the most lethal cancers and its prognosis is extremely poor. Clarification of molecular mechanisms and identification of prognostic biomarkers are urgently needed. Though we previously found that LGMN was involved in pancreatic carcinoma progression, the upstream regulation of LGMN remains unknown. We used reliable software to search for the potential transcription factors that may be related with LGMN transcription, we found that ELK1 could be a new regulator of LGMN transcription that binded directly to the LGMN promoter. Moreover, knocking down of ELK1 reduced pancreatic cancer cells proliferation, invasion and survival, while LGMN restored the malignancy of pancreatic cancer in vitro and in vivo. Overexpression of ELK1 further increased cancer cells proliferation, invasion and survival. Clinically, ELK1 and LGMN were positively correlated with clinical stage, degree of differentiation and Lymph node infiltration. ELK1 and LGMN were identified as independent prognostic factors for overall survival. The patients with low expression of ELK1/LGMN survived an average of 29.65 months, whereas those with high expression of ELK1/LGMN survived an average of 16.67 months. In conclusive, our results revealed a new mechanism by which ELK1 promoted the progression of pancreatic cancer via LGMN and conferred poor prognosis.</p

Image1_ELK1 Enhances Pancreatic Cancer Progression Via LGMN and Correlates with Poor Prognosis.TIF

Pancreatic cancer is one of the most lethal cancers and its prognosis is extremely poor. Clarification of molecular mechanisms and identification of prognostic biomarkers are urgently needed. Though we previously found that LGMN was involved in pancreatic carcinoma progression, the upstream regulation of LGMN remains unknown. We used reliable software to search for the potential transcription factors that may be related with LGMN transcription, we found that ELK1 could be a new regulator of LGMN transcription that binded directly to the LGMN promoter. Moreover, knocking down of ELK1 reduced pancreatic cancer cells proliferation, invasion and survival, while LGMN restored the malignancy of pancreatic cancer in vitro and in vivo. Overexpression of ELK1 further increased cancer cells proliferation, invasion and survival. Clinically, ELK1 and LGMN were positively correlated with clinical stage, degree of differentiation and Lymph node infiltration. ELK1 and LGMN were identified as independent prognostic factors for overall survival. The patients with low expression of ELK1/LGMN survived an average of 29.65 months, whereas those with high expression of ELK1/LGMN survived an average of 16.67 months. In conclusive, our results revealed a new mechanism by which ELK1 promoted the progression of pancreatic cancer via LGMN and conferred poor prognosis.</p

Table2_ELK1 Enhances Pancreatic Cancer Progression Via LGMN and Correlates with Poor Prognosis.DOC

Pancreatic cancer is one of the most lethal cancers and its prognosis is extremely poor. Clarification of molecular mechanisms and identification of prognostic biomarkers are urgently needed. Though we previously found that LGMN was involved in pancreatic carcinoma progression, the upstream regulation of LGMN remains unknown. We used reliable software to search for the potential transcription factors that may be related with LGMN transcription, we found that ELK1 could be a new regulator of LGMN transcription that binded directly to the LGMN promoter. Moreover, knocking down of ELK1 reduced pancreatic cancer cells proliferation, invasion and survival, while LGMN restored the malignancy of pancreatic cancer in vitro and in vivo. Overexpression of ELK1 further increased cancer cells proliferation, invasion and survival. Clinically, ELK1 and LGMN were positively correlated with clinical stage, degree of differentiation and Lymph node infiltration. ELK1 and LGMN were identified as independent prognostic factors for overall survival. The patients with low expression of ELK1/LGMN survived an average of 29.65 months, whereas those with high expression of ELK1/LGMN survived an average of 16.67 months. In conclusive, our results revealed a new mechanism by which ELK1 promoted the progression of pancreatic cancer via LGMN and conferred poor prognosis.</p

Image4_ELK1 Enhances Pancreatic Cancer Progression Via LGMN and Correlates with Poor Prognosis.TIF

Pancreatic cancer is one of the most lethal cancers and its prognosis is extremely poor. Clarification of molecular mechanisms and identification of prognostic biomarkers are urgently needed. Though we previously found that LGMN was involved in pancreatic carcinoma progression, the upstream regulation of LGMN remains unknown. We used reliable software to search for the potential transcription factors that may be related with LGMN transcription, we found that ELK1 could be a new regulator of LGMN transcription that binded directly to the LGMN promoter. Moreover, knocking down of ELK1 reduced pancreatic cancer cells proliferation, invasion and survival, while LGMN restored the malignancy of pancreatic cancer in vitro and in vivo. Overexpression of ELK1 further increased cancer cells proliferation, invasion and survival. Clinically, ELK1 and LGMN were positively correlated with clinical stage, degree of differentiation and Lymph node infiltration. ELK1 and LGMN were identified as independent prognostic factors for overall survival. The patients with low expression of ELK1/LGMN survived an average of 29.65 months, whereas those with high expression of ELK1/LGMN survived an average of 16.67 months. In conclusive, our results revealed a new mechanism by which ELK1 promoted the progression of pancreatic cancer via LGMN and conferred poor prognosis.</p

Image2_ELK1 Enhances Pancreatic Cancer Progression Via LGMN and Correlates with Poor Prognosis.TIF

Pancreatic cancer is one of the most lethal cancers and its prognosis is extremely poor. Clarification of molecular mechanisms and identification of prognostic biomarkers are urgently needed. Though we previously found that LGMN was involved in pancreatic carcinoma progression, the upstream regulation of LGMN remains unknown. We used reliable software to search for the potential transcription factors that may be related with LGMN transcription, we found that ELK1 could be a new regulator of LGMN transcription that binded directly to the LGMN promoter. Moreover, knocking down of ELK1 reduced pancreatic cancer cells proliferation, invasion and survival, while LGMN restored the malignancy of pancreatic cancer in vitro and in vivo. Overexpression of ELK1 further increased cancer cells proliferation, invasion and survival. Clinically, ELK1 and LGMN were positively correlated with clinical stage, degree of differentiation and Lymph node infiltration. ELK1 and LGMN were identified as independent prognostic factors for overall survival. The patients with low expression of ELK1/LGMN survived an average of 29.65 months, whereas those with high expression of ELK1/LGMN survived an average of 16.67 months. In conclusive, our results revealed a new mechanism by which ELK1 promoted the progression of pancreatic cancer via LGMN and conferred poor prognosis.</p

Image3_ELK1 Enhances Pancreatic Cancer Progression Via LGMN and Correlates with Poor Prognosis.TIF

Pancreatic cancer is one of the most lethal cancers and its prognosis is extremely poor. Clarification of molecular mechanisms and identification of prognostic biomarkers are urgently needed. Though we previously found that LGMN was involved in pancreatic carcinoma progression, the upstream regulation of LGMN remains unknown. We used reliable software to search for the potential transcription factors that may be related with LGMN transcription, we found that ELK1 could be a new regulator of LGMN transcription that binded directly to the LGMN promoter. Moreover, knocking down of ELK1 reduced pancreatic cancer cells proliferation, invasion and survival, while LGMN restored the malignancy of pancreatic cancer in vitro and in vivo. Overexpression of ELK1 further increased cancer cells proliferation, invasion and survival. Clinically, ELK1 and LGMN were positively correlated with clinical stage, degree of differentiation and Lymph node infiltration. ELK1 and LGMN were identified as independent prognostic factors for overall survival. The patients with low expression of ELK1/LGMN survived an average of 29.65 months, whereas those with high expression of ELK1/LGMN survived an average of 16.67 months. In conclusive, our results revealed a new mechanism by which ELK1 promoted the progression of pancreatic cancer via LGMN and conferred poor prognosis.</p

Image5_ELK1 Enhances Pancreatic Cancer Progression Via LGMN and Correlates with Poor Prognosis.PNG

Pancreatic cancer is one of the most lethal cancers and its prognosis is extremely poor. Clarification of molecular mechanisms and identification of prognostic biomarkers are urgently needed. Though we previously found that LGMN was involved in pancreatic carcinoma progression, the upstream regulation of LGMN remains unknown. We used reliable software to search for the potential transcription factors that may be related with LGMN transcription, we found that ELK1 could be a new regulator of LGMN transcription that binded directly to the LGMN promoter. Moreover, knocking down of ELK1 reduced pancreatic cancer cells proliferation, invasion and survival, while LGMN restored the malignancy of pancreatic cancer in vitro and in vivo. Overexpression of ELK1 further increased cancer cells proliferation, invasion and survival. Clinically, ELK1 and LGMN were positively correlated with clinical stage, degree of differentiation and Lymph node infiltration. ELK1 and LGMN were identified as independent prognostic factors for overall survival. The patients with low expression of ELK1/LGMN survived an average of 29.65 months, whereas those with high expression of ELK1/LGMN survived an average of 16.67 months. In conclusive, our results revealed a new mechanism by which ELK1 promoted the progression of pancreatic cancer via LGMN and conferred poor prognosis.</p