The Prognostic Value of Combination of Plasma Fibrinogen and CA19-9 in Non-Distant Metastatic Breast Cancer Patients Undergoing Surgery.

PURPOSE: This article aimed to study the prognostic value of preoperative plasma fibrinogen and CA19-9 in non-distant metastatic breast cancer (BC). PATIENTS AND METHODS: A total of 343 non-distant metastatic BC patients were included in this study. The optimal cut-off values of plasma fibrinogen and CA19-9 were obtained by receiver operating characteristic (ROC) curve analysis. Univariate and multivariate Cox regression analyses were used to evaluate prognostic factors for overall survival (OS). Survival data were assessed using Kaplan-Meier survival analysis with the Log-rank test. Based on the cut-off values, we classified the fibrinogen-CA19-9 score as follows: 2 (both hyperfibrinogenemia and high CA19-9), 1 (either hyperfibrinogenemia or high CA19-9), and 0 (neither hypefibrinogenemia nor high CA19-9). RESULTS: Our follow-up time totaled 10 years, the median follow-up time was 77 months (range=2-119 months), and 82 (23.9%) of 343 patients died during the follow-up period. The optimal cut-off values of plasma fibrinogen and CA19-9 were 2.805 g/L and 11.85 U/mL, respectively. The multivariate Cox analysis results suggested that there was a significant association between worse OS and elevated preoperative plasma fibrinogen and CA19-9 levels (HR=2.016, 95% CI=1.216-3.342, P=0.007; and HR=2.042, 95% CI=1.282-3.253, P=0.003). The area under the ROC curve (AUC) increased from 0.589 (for plasma fibrinogen) and 0.594 (for CA19-9) to 0.640 when these two parameters were combined. When we added this combined factor to the multivariate analysis, it was an independent prognostic factor for BC (P<0.001). According to the above results, we chose four prognostic factors to construct our nomogram. The AUC was 0.724, which indicates that the nomogram performs well. CONCLUSION: The combination of plasma fibrinogen and CA19-9 could be used as a valid independent prognostic factor for non-distant metastatic BC compared with either parameter alone and could easily be applied in clinical practice.

LOC389641 promotes papillary thyroid cancer progression by regulating the EMT pathway.

Aim: Thyroid cancer (TC) is one of the most common types of endocrine malignancy and poses a significant challenge to human health. The long noncoding RNA 389641 (LOC389641) has been found to be associated with many types of cancer. However, the function of LOC389641 in papillary TC (PTC) remains unknown. Our aim is to explore LOC389641 expression and its role in TC. Materials & methods: The function of LOC389641 was determined by colony formation, migration and invasion assays in PTC. Western blot assays were performed to determine the biomarker of epithelial-mesenchymal transition. Results: In this study, we show that LOC389641 is involved in PTC, which suggests that it may be a target for TC therapies.

Lysophosphatidic Acid Receptor 5 (LPAR5) Plays a Significance Role in Papillary Thyroid Cancer via Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin (mTOR) Pathway.

BACKGROUND Thyroid cancer is the most common endocrine system malignancy. Scientists have done considerable research into the molecular mechanisms involved, but many mechanisms remain undiscovered. MATERIAL AND METHODS We performed a comprehensive analysis of the whole-transcriptome resequencing derived from thyroid tissues and paired papillary thyroid cancer (PTC) and showed that lysophosphatidic acid receptor 5 (LPAR5) is strongly overexpressed in thyroid carcinoma. Then, we used TPC-1 and KTC-1 to explore the effect of LPAR5 knockdown on colony formation, migration, proliferation, invasion, and apoptosis of PTC cell line cells. AKT activator was used for the recovery test. Finally, we designed proteomic experiments to explore the role of LPAR5 in the AKT pathway and the EMT process. RESULTS Cell function experiments showed that LPAR5 knockdown can significantly induce apoptosis of KTC-1 and TPC-1 cells. Furthermore, LPAR5 can promote PTC metastasis and tumorigenesis by activating the PI3K/AKT pathway and decreasing its cancer-promoting effect when using AKT agonist. We also found that LPAR5 can regulate the expression of EMT-related proteins, which affect invasion and migration. CONCLUSIONS In summary, downregulation of LPAR5 expression can inhibit the physiological process of PTC, and this phenomenon is related to the PI3K/AKT pathway and EMT.

Scavenger receptor class A, member 5 is associated with thyroid cancer cell lines progression via epithelial-mesenchymal transition.

Thyroid cancer (TC) has become one of most common endocrine malignancies in recent decades. Due to gene background polymorphism, it's outcome goes quite differently in each patient. For exploring the mechanism, we performed whole transcriptome sequencing of paired papillary thyroid carcinoma (PTC) and adjacent thyroid tissues. As a result, scavenger receptor class A member 5 (SCARA5) might be a crucial anti-oncogene associated with PTC. By RT-qPCR, we first detected the expression of SCARA5 in PTC tissue and three type of TC cell lines. Besides, The Cancer Genome Atlas (TCGA) data were gathered to analysis the relationship between SCARA5 and clinical feature. A series of loss-function experiments in TC cell lines (KTC-1 and BCPAP) to investigate the function of SCARA5 in PTC. The results showed that SCARA5 expression in PTC was lower than adjacent normal tissue. And, it's consistent with the TCGA database. After analyse the correlation between SCARA5 expression and clinicopathological features in TCGA database, we discovered that downregulated SCARA5 is significantly connected age (P = .04) and tumour size (P = .032). Knockdown of SCARA5 in TC cell line could significantly increase the function of cells proliferation, colony formation, migration, and invasion. Furthermore, we also proved that SCARA5 could modulate the expression of epithelial-mesenchymal transition-related proteins, which influence invasion and migration. To best of our knowledge, SCARA5 is a suppressor gene which was associated with PTC and might be a potential therapeutic target in the future. SIGNIFICANCE OF THE STUDY: Thyroid cancer (TC) has become one of most common endocrine malignancies in recent decades. By whole transcriptome sequencing of paired papillary thyroid carcinoma (PTC) and adjacent thyroid tissues, author discovered that scavenger receptor class A member 5 (SCARA5) might be crucial anti-oncogene associated with PTC. Furthermore, knocking-down of SCARA5 in TC cell line can increase the function of cells proliferation, colony formation, migration, and invasion. Author also proved that SCARA5 could modulate the expression of epithelial-mesenchymal transition-related proteins.

Growth-associated protein 43 promotes thyroid cancer cell lines progression via epithelial-mesenchymal transition.

Thyroid cancer is maintaining at a high incidence level and its carcinogenesis is mainly affected by a complex gene interaction. By analysis of the next-generation resequencing of paired papillary thyroid cancer (PTC) and adjacent thyroid tissues, we found that Growth Associated Protein 43 (GAP43), a phosphoprotein activated by protein kinase C, might be novel markers associated with PTC. However, its function in thyroid carcinoma has been poorly understood. We discovered that GAP43 was significantly overexpressed in thyroid carcinoma and these results were consistent with that in The Cancer Genome Atlas (TCGA) cohort. In addition, some clinicopathological features of GAP43 in TCGA database showed that up-regulated GAP43 is significantly connected to lymph node metastasis (P < 0.001) and tumour size (P = 0.038). In vitro experiments, loss of function experiments was performed to investigate GAP43 in PTC cell lines (TPC-1 and BCPAP). The results proved that GAP43 knockdown in PTC cell significantly decreased the function of cell proliferation, colony formation, migration, and invasion and induced cell apoptosis. Furthermore, we also indicated that GAP43 could modulate the expression of epithelial-mesenchymal transition-related proteins, which could influence invasion and migration. Put those results together, GAP43 is a gene which was associated with PTC and might be a potential therapeutic target.

Original tumour suppressor gene polycystic kidney and hepatic disease 1-like 1 is associated with thyroid cancer cell progression.

In recent decades, thyroid cancer (TC) has become one of the most common endocrine malignancies. Next-generation sequencing of paired TC and adjacent healthy thyroid tissues demonstrated that polycystic kidney and hepatic disease 1-like 1 (PKHD1L1) may serve as a tumour suppressor gene in thyroid cancer. However, the function of PKHD1L1 in thyroid cancer is still unknown. To validate the results of whole-transcriptome resequencing, the expression levels of PKHD1L1 were evaluated in 58 pairs of papillary thyroid cancer (PTC) tissue samples and three thyroid cancer cell lines. In addition, The Cancer Genome Atlas (TCGA) data were used to analyse the relationship between PKHD1L1 and patient clinicopathological features. Cell Counting Kit-8, colony formation, migration and invasion assays were performed to assess the effects of PKHD1L1 knockdown in three TC cell lines. PKHD1L1 expression was significantly lower in thyroid carcinoma compared with that in matched normal tissue, and this result was consistent with that in TCGA cohort. TCGA data demonstrated that PKHD1L1 downregulation was associated with a number of aggressive clinicopathological features, such as histological type, lymph node metastasis (LNM), distant metastasis, tumour size and clinical stage. Logistic regression analysis of data from patients with PTC revealed that PKHD1L1 expression, histological type, age and tumour size were independent high-risk factors for LNM. The PKHD1L1 biological function was investigated in the three TC cell lines: TPC-1, KTC1 and BCPAP. A loss of function experiment demonstrated that PKHD1L1 knockdown promoted cell proliferation, colony formation and cell invasion in TC cell lines. In conclusion, PKHD1L1 may be a tumour suppressor gene associated with PC, and may be a potential therapeutic target in the future.

NECTIN4 promotes papillary thyroid cancer cell proliferation, migration, and invasion and triggers EMT by activating AKT.

Papillary thyroid cancer (PTC) is the most frequent type of malignant thyroid cancer, but its molecular mechanisms remain unknown. To better understand the tumorigenesis and progression of PTC, we conducted a comprehensive analysis of the whole-transcriptome resequencing of paired PTC and normal thyroid tissues. Nectin cell adhesion molecule 4 (NECTIN4) was significantly overexpressed in thyroid carcinoma compared with that in matched normal tissue. We also assessed the relation between the expression level of NECTIN4 and the clinicopathological features of PTC in The Cancer Genome Atlas database, and results showed that upregulated NECTIN4 is associated with lymph node metastasis (P<0.001) and tumor size (P=0.017). The biological function of NECTIN4 was also investigated by using the PTC cell lines TPC-1 and KTC-1. In vitro experiments demonstrated that NECTIN4 downregulation significantly inhibits the colony formation, proliferation, migration, and invasion of PTC cell lines. NECTIN4 could modulate the expression of epithelial-mesenchymal transition-related proteins via the PI3K/AKT pathway, and SC79, an AKT phosphorylation activator, could reverse the si-RNA knockdown effect. In addition, after the use of AKT inhibitors (LY 294,002), we found that SiRNA have similar effect with AKT inhibitors. Taking the results together, the current study shows that NECTIN4 has important biological implications in the tumorigenesis and metastasis of PTC and may be a potential therapeutic target for the disease.

COPB2 is up-regulated in breast cancer and plays a vital role in the metastasis via N-cadherin and Vimentin.

Breast cancer (BC) is a common malignant tumour for the adult female and its relative incidence has increased continuously in recent years. The primary molecular mechanisms of breast tumourigenesis remain unclear. With the sequencing technology, we found that coatomer protein complex subunit beta 2 (COPB2) gene is overexpressed in breast cancer tissues. However, the biological function of COPB2 in BC has yet to be determined. This current research demonstrates, significant up-regulation of COPB2 in tissues of breast cancer while comparing the adjacent normal tissue both invalidated cohort and TCGA cohort. Up-regulated expression of COPB2 was correlated with lymph node metastasis (LNM) and oestrogen receptor (ER) in the TCGA cohort and a high level of COPB2 was associated with age and lymph node metastasis in the validated cohort. Besides, logistic analysis illustrated in BC patient COPB2 expression, tumour size, age, ER and disease stage were independent high-risk factors of LNM. Loss of function experiments revealed that down-regulation of COPB2 could inhibit capacities of proliferation and cell invasion in MDA-MB-231 and BT-549 cell lines. Moreover, underexpression of COPB2 could decrease the EMT-related protein N-cadherin and vimentin which may lead to cell invasion. This current research provides new shreds of evidence that COPB2 overexpression shows significant character in the progression of breast cancer. To best of our knowledge, our findings indicated that COPB2 was vital oncogene which was associated with breast cancer.

Low metallothionein 1M (MT1M) is associated with thyroid cancer cell lines progression.

Papillary thyroid cancer (PTC) is the most common malignancy of the thyroid carcinoma, despite ongoing advances, novel biomarkers are required for prognosis and diagnosis of PTC. Our previous research found that metallothionein 1M (MT1M) was a novel potential PTC associated gene in thyroid cancer. In the present study, the expression status and prognostic value of MT1M expression were investigated in thyroid cancer. Tissue samples from 60 patients with PTC were subjected to the quantitative real-time polymerase chain reaction and the relative expression of MT1M in the patient tissue was evaluated. The Cancer Genome Atlas (TCGA) RNA-seq database was downloaded to further explore the role of MT1M in PTC and its relationship with lymph node metastasis (LNM). Logistic analysis showed that reduced expression of MT1M, histological type, and clinical stage are independent high-risk factors for LNM in PTC. The biological function of MT1M was also researched by using the PTC cell lines TPC-1, KTC1 and BCPAP. In vitro experiments revealed that MT1M upregulation significantly inhibits the colony formation, proliferation, migration, and invasion of PTC cell lines. We also found that MT1M could modulate the expression of N-cadherin and vimentin. These results implied that MT1M involved in the progress of thyroid cancer and might act as a tumor suppressor gene. In this study, we identified, for the first time, MT1M was involved in thyroid carcinoma cell lines This study specified a potential new marker and a target for gene therapy in thyroid cancer treatment.