Node TNM Research Articles

Upregulation of long noncoding RNA linc02544 and its association with overall survival rate and the influence on cell proliferation and migration in lung squamous cell carcinoma

BackgroundLong noncoding RNAs (lncRNAs) exert crucial biological functions by regulating miRNAs, which are implicated in cancer progression and tumorigenesis. A previous study has indicated that lncRNA linc02544 expression is upregulated in lung adenocarcinoma, whereas, the role of linc02544 in LUSC is elusive.MethodsThe differential linc02544 expression in LUSC tissues and adjacent non-tumor tissues were evaluated with RT-qPCR. Kaplan-Meier curve was conducted to evaluate the clinical prognostic significance of linc02544. Then cellular experiments were performed to assess the influence of linc02544 in LUSC proliferation, invasion, and migration, and a western blot assay was used to measure the metastasis-related protein levels. The downstream miRNAs were verified using the LncBase Experimental v.2 database and dual-luciferase reporter assay.ResultsLinc02544 was overexpressed in LUSC tissues from positive lymph node metastasis-positive and TNM high-stage patients. Low linc02544 expression was associated with a longer survival rate. Downregulation of linc02544 by si-linc02544 restrained cell growth capacities, migration, and invasion abilities. Expression of MMP-2, MMP-9, and vimentin was decreased while E-cadherin was increased in si-linc02544 cells compared with that in untreated cells. Mechanistically, we identified that linc02544 acted as a sponge of miR-138-5p, which expression had a negative correlation. E2F3 was a potential target of miR-138-5p,ConclusionsNotably, high linc02544 expression was associated with severe clinical parameters and was a putative prognostic predictor for patients with LUSC. Downregulation of linc02544 may weaken the LUSC cell proliferation, migration, and invasion by regulating miR-138-5p/E2F3, which maybe serve as a biomarker for the prognosis and target treatment of LUSC.

Expression of miR-4739 in Gastric cancer and its Relationship with Clinical Pathological Features of Patients.

ObjectiveTo investigate the expression level of miR-4739 in gastric cancer (GC), analyze its diagnostic value in GC and the relationship with clinical pathological characteristics, and analyze its impact on the prognosis of patients.MethodsA total of 96 patients with GC who underwent radical gastrectomy in our hospital from March 2017 to June 2021 were selected. GC tissues from all patients were collected, and normal tissues adjacent to cancer were collected as controls. The expression level of miR-4739 in tissues was detected, the relationship between miR-4739 and different pathological features was analyzed, and the diagnostic value of miR-4739 in GC was analyzed. All patients were followed up after the operation, and the survival time of the patients was set as from the day of the first operation to 1 d when the patients died or the follow-up ended.ResultsThe relative expression level of miR-4739 in the GC tissue was (0.39 ± 0.06), lower than that in the paracancerous tissue (1.18 ± 0.19) (P < 0.05). The AUC of miR-4739 in the diagnosis of GC was 0.705. When the Youden index was 0.320 and the optimal cutoff value was 0.37, the sensitivity was 95.30% and the specificity was 36.70%. The expression level of miR-4739 in our patient was related to the differentiation degree, lymph node metastasis, tumor diameter, and TNM stage (P < 0.05). During the follow-up period, 26 of 96 patients died, and the survival rate was 72.92% (26/96). The median survival time was 29 months in the miR-4739 LE group, which was shorter than 39 months in the miR-4739 HE group (P < 0.05). Univariate analysis showed that age, degree of differentiation, lymph node metastasis, tumor diameter, TNM staging, and miR-4739 expression were all related to the prognosis of the patient (P < 0.05). Multivariate analysis showed that differentiation degree, lymph node metastasis, tumor diameter, TNM staging, and miR-4739 expression were all independent factors affecting the prognosis of the patients (P < 0.05).ConclusionThe expression of miR-4739 in GC tissue was down-regulated, and its level was related to the degree of differentiation, lymph node metastasis, tumor diameter, and TNM stage. The expression level of miR-4739 has certain diagnostic value for patients with GC, and the prognosis of patients in LE group was worse than that in HE group.

Differential expression of Tim3 protein in colorectal cancer associated with MSI and Braf mutation.

Tim3 is a negative immune checkpoint molecule and plays a crucial part in tumor-induced immune suppression. Tim3 is a cell surface molecule expressed on T cells marking dysfunctional CD8+ cells in various kinds of cancers. Tim3 expression was mainly reported in tumor-infiltrating lymphocytes (TILs). There are few studies focusing on the expression of Tim3 in tumor cells. Immunohistochemistry was performed to determine Tim3 expression level. The relationships between Tim3 expression in colorectal cancer cells and in tumor-infiltrating lymphocytes and cilicopathological parameters were statistically analyzed. Tim3 was differentially detected in TILs and in colorectal cancer cells. Positive expression of Tim3 in colorectal cancer cells was associated with tumor location (P=0.001), depth of tumor invasion (P<0.001), lymph node metastasis (P=0.001), TNM stage (P=0.001), MSI (P=0.008), and Braf V600E mutation (P=0.001). On the other hand, positive expression of Tim3 in TILs was only related to depth of tumor invasion (P<0.001). Positive expression of Tim3 in both colorectal cancer cells and TILs was associated with depth of tumor invasion (P<0.001), lymph node metastasis (P=0.002), TNM stage (P=0.002), MSI (P=0.039), and Braf V600E mutation (P=0.009). Kaplan-Meier survival analysis showed that Tim3 expression in colorectal cancer and in TILs was significantly associated with patient overall survival (OS) rate (P=0.039, and 0.001). Tim3 may be a potential prognostic marker and a therapy target for colorectal cancer.

CircRPAP2 regulates the alternative splicing of PTK2 by binding to SRSF1 in breast cancer

Breast cancer is the most commonly diagnosed malignant tumor and the second-highest cause of cancer-related deaths in women worldwide. Circular RNAs (circRNAs) are associated with the development of numerous cancers, including breast cancer. Here, we present the first report that circRPAP2 (hsa_circ_0000091) is downregulated in breast cancer tissue samples and cell lines. Furthermore, the expression level of circRPAP2 in breast cancer tissues was correlated with axillary lymph node metastasis and TNM stage. Biological function studies demonstrated that circRPAP2 inhibited the proliferation and migration of breast cancer in vivo and in vitro. The mechanistic evaluation indicated that circRPAP2 can bind to the oncoprotein SRSF1, likely competing with the binding between SRSF1 and PTK2 pre-mRNA, thereby attenuating SRSF1-mediated alternate splicing of PTK2, an effector of SRSF1 oncogenic activity, resulting in the reduction of PTK2 mRNA and protein expression. Overall, our findings suggest that circRPAP2 plays a tumor suppressor role and may serve as a biomarker in breast cancer. In addition, the identification of the circRPAP2/SRSF1/PTK2 axis provides new insights into the pathogenesis of breast cancer and highlights a novel target for the development of oncotherapeutics.

Reticulon 2 promotes gastric cancer metastasis via activating endoplasmic reticulum Ca2+ efflux-mediated ERK signalling

Gastric cancer ranks fourth for mortality globally among various malignant tumours, and invasion and metastasis are the major reason leading to its poor prognosis. Recently, accumulating studies revealed the role of reticulon proteins in cell growth and transmigration. However, the expression and biological function of reticulon proteins in human gastric cancer remain largely unclear. Herein, we explored the potential role of reticulon 2 (RTN2) in the progression of gastric cancer. Tissue microarray was used to determine the expression levels of RTN2 in 267 gastric cancer patients by immunohistochemistry. Gastric cancer cell lines were utilised to examine the influences of RTN2 on cellular migration and invasion abilities, epithelial-to-mesenchymal transition (EMT) and signalling pathway. In vivo studies were also performed to detect the effect of RTN2 on tumour metastasis. We found that RTN2 expression was notably upregulated in tumour tissues compared to pericarcinomatous tissues. High RTN2 expression was positively correlated with patients’ age, vessel invasion, tumour invasion depth, lymph node metastasis and TNM stage. Besides, high RTN2 staining intensity was associated with adverse survival which was further identified as an independent prognostic factor for gastric cancer patients by multivariate analysis. And the predictive accuracy was also improved when incorporated RTN2 into the TNM-staging system. RTN2 could promote the proliferation, migration and invasion of gastric cancer cells in vitro and lung metastasis in vivo. Mechanistically, RTN2 interacted with IP3R, and activated ERK signalling pathway via facilitating Ca2+ release from the endoplasmic reticulum, and subsequently drove EMT in gastric cancer cells. These results proposed RTN2 as a novel promotor and potential molecular target for gastric cancer therapies.

The E3 ubiquitin ligase, FBXW5, promotes the migration and invasion of gastric cancer through the dysregulation of the Hippo pathway

F-box and WD repeat domain-containing 5 (FBXW5), with WD40 repeats, can bind to the PPxY sequence of the large tumor suppressor kinases 1/2 (LATS1/2) kinase domain, resulting in ubiquitination. Ubiquitination and the subsequent degradation of LATS1/2 abrogate the Hippo pathway and worsen gastric cancer (GC). However, the effects and molecular mechanisms of FBXW5 in GC remain unexplored. To elucidate the clinical significance of FBXW5, immunohistochemistry was conducted to reveal the positive correlation between FBXW5 expression and lymph node metastasis (p < 0.001) and TNM stage (training cohort: p = 0.018; validation cohort: p = 0.001). Further, patients with high FBXW5 expression were found to have poor prognosis (training cohort: log-rank p = 0.020; validation cohort: log-rank p = 0.025). Cell experiments revealed the promoting effects of FBXW5 on the proliferation, invasion, metastasis, and chemoresistance of GC cells. Blocking LATS1-YAP1 leads to the loss of FBXW5-mediated regulation of the Hippo pathway and partial functions. Further, co-immunoprecipitation and in vivo ubiquitination assays revealed the interaction between FBXW5 and LATS1, which promoted the ubiquitination and degradation of LATS1. Based on mouse xenograft assays, FBXW5 silencing attenuated the growth of subcutaneous tumor xenografts. Altogether, FBXW5 was found to inactivate the Hippo signaling pathway by enhancing LATS1 ubiquitination and degradation, which promoted the invasion, metastasis, and drug resistance of GC cells.

Clinicopathological significance of HSP70 expression in gastric cancer: a systematic review and meta-analysis

BackgroundHeat shock protein 70 (HSP70) has been associated with the clinicopathological characteristics and prognosis of many cancers types, implying that it is a potential cancer biomarker. However, no consensus has been reached regarding its clinicopathological and prognostic significance in patients with gastric cancer. To address this gap, we performed a systematic review and meta-analysis.MethodsWe searched PubMed, Embase, and the Cochrane Library for full-text literature according to the eligibility criteria. We used the odds ratio and hazard ratio as the suitable parameters to evaluate the clinicopathological and prognostic significance of HSP70. The statistical analysis was performed using STATA 15.0.ResultsAfter inclusion and exclusion of studies based on the eligibility criteria, data of 1,307 patients with gastric cancer from 9 studies were finally included. The pooled outcomes implied that HSP70 expression was significantly correlated with higher differentiation degrees, intestinal gastric cancer, and lymphovascular invasion but not with age, gender, depth of invasion, Helicobacter pylori infection, lymph node invasion, TNM stages, and metastasis. The pooled HR showed no significant correlation between HSP70 expression and overall survival of gastric cancer patients.ConclusionsOur meta-analysis showed that HSP70 plays a complicated role in the development of gastric cancer. It may be directly engaged in tumour differentiation and distant invasion but cannot be considered a biomarker for predicting the prognosis of gastric cancer.

243 PROGNOSTIC IMPACT OF CXCR7 AND CXCL12 EXPRESSION IN PATIENTS WITH ESOPHAGEAL ADENOCARCINOMA

Abstract Chemokines are major regulators of cell trafficking and adhesion. The chemokine CXCL12 and its receptors, CXCR4 and CXCR7, have recently been reported as biomarkers in various cancers, including esophageal squamous cell carcinoma; however, there are few studies of these chemokines in esophageal adenocarcinoma (EAC). In this study, we investigated the relationship between expression of CXCL12, CXCR4 and CXCR7, and prognosis in patients with EAC. Methods This study examined 55 patients with EAC who were treated in Toronto General Hospital from 2001 to 2010. Tissue microarray immunohistochemistry was used to evaluate the expression of CXCL12, CXCR4 and CXCR7. Evaluation of immunohistochemistry was performed by a pathologist without knowledge of patients’ information and scored based on a semiquantitative scoring system. The average score from multiple cancer tissues on the microarray was utilized and patients were divided into high or low expression groups using the median score as a cutoff point. These results were compared with the patients’ clinicopathological features and survival. Results The score of CXCR7 was positively correlated with that of CXCL12 (r = 0.3154). High CXCR7 expression was significantly associated with lymphatic invasion (present vs absent, P = 0.005), higher number of lymph node metastases (pN0–1 vs pN2–3, P = 0.0014) and TNM stage (Stage I-II vs III-IV, P = 0.0168). Patients with high CXCR7 (n = 23) expression was associated with worse overall (OS) and disease-free survival (DFS) (P = 0.0221, 0.0090, respectively), and patients with high CXCL12 (n = 24) tended to have worse OS and DFS (P = 0.1091, 0.1477, respectively). High expression of both CXCR7 and CXCL12 was an independent prognostic factor for DFS on multivariable analysis (HR0.3, 95%CI: 0.1–0.8, P = 0.0115). Conclusion High CXCR7 expression was associated with poor prognosis in patients with EAC, and high expression of CXCR7 and its ligand CXCL12, had a stronger association on prognosis. Further study of this potential biomarker using whole tissue samples and larger sample size is warranted.

Expression and mechanism of exosome-mediated A FOXM1 related long noncoding RNA in gastric cancer

BackgroundForkhead box protein M1 (FOXM1) is an oncogene regulating tumor growth and metastasis. Exosome was suggested to mediate cell communication by delivering active molecules in cancers. However, the existence of FOXM1 in circulating exosomes and the role of exosome FOXM1 in gastric cancer (GC) were not clear. This study aims to investigate the potential role of FOXM1 related long noncoding RNA (FRLnc1) in exosomes in GC.ResultsThe prepared CD63 immunomagnetic beads (CD63-IMB) had the characteristics of good dispersity and high magnetic response. The isolated exosomes were presented with elliptical membranous particles under a transmission electron microscope (TEM), with the particle size of 89.78 ± 4.8 nm. Western blot (WB) results showed that the exosomes were rich in CD9 and CD81. The Dil-labeled exosomes were distributed around cytoplasm and nucleus of cells by imaging flow cytometry (IFC) analysis. The results of quantitative real-time PCR (qRT-PCR) revealed that the FRLnc1 expressions were up-regulated in GC cells, tumor tissues, and serum of GC patients. An obviously up-regulated FRLnc1 expression was found in serum exosomes of GC patients. Up-regulation of FRLnc1 expression was closely correlated to lymph node metastasis (LNM) and TNM stage with the combination of relevant clinicopathological parameter analysis. The in vitro functional analyses demonstrated that FRLnc1 knockdown by RNA interference suppressed cell proliferation and migration in HGC-27 cells, whereas FRLnc1 overexpression promoted cell proliferation and migration in MKN45 cells. After exosome treatment, the FRLnc1 expression was significantly increased in MKN45 cells, and the MKN45 cells showed increased ability of proliferation and migration.ConclusionGC cells-derived exosomes played roles in promoting the growth and metastasis of GC by transporting FRLnc1, suggesting that FRLnc1 in the exosomes may be a potential biomarker for the diagnosis and treatment of GC. The delivery of FRLnc1 by the exosomes may provide a new way for the treatment of GC.Trial registration 2020-KYSB-094. Registered 23 March 2020—Retrospectively registeredGraphic abstract

Abstract PS4-41: Salt-inducible kinases suppress tumour function and regulate drug resistance in breast cancer

Abstract Background: Salt-inducible kinases (SIKs) belonging to an AMP-activated kinase (AMPK) family, have functions in tumourgeniesis and metastasis in many solid tumours. However, the role of SIKs in breast cancer is not clear. In this study we aimed to determine the function of SIKs (SIK1, SIK2 and SIK3) in human breast cancer. Method: A cohort of breast cancer tissues (n=102) were analysed using qPCR to determine changes in SIK expression (SIK1, SIK2, SIK3 and housekeeping GAPDH ) between cancer and normal tissues and different aetiologies of cancer. In addition, a breast disease spectrum array (TMA) was probed for SIK expression at the protein level. SIK1, 2 and 3 were knocked down using shRNA in the human breast cancer cell lines MCF-7 and MDA-MB-231 and changes in cell behaviour were assessed using a number of cell function assays.Results: At the messenger level, expression of SIK2 was lower in breast cancer than normal tissue (p=0.0179), while expression of SIK1 and SIK3 had no significant difference between breast cancer and normal tissue. SIK3 expression was associated with ER status in the cohort (p=0.02). The level of SIK2 expression was significantly different in Stage I and Stage III. While SIK3 expression was significantly higher in ER positive breast cancer than ER negative breast cancer. Further analysis using Kaplan-Meier survival was performed for SIKs expression in an online database (http://kmplot.com/analysis/index.php?p=background) which showed that that an increased expression of SIKs was associated with good prognosis in the breast cancer cohort (p&amp;lt;0.01). Moreover, IHC staining correlation of SIKs in tumour with different clinicopathological characteristics showed a SIK1 Klein score significantly higher in ER positive breast cancer than ER negative breast cancer; in SIK3, a higher Klein score was observed in breast cancer with higher Grade, negative lymph node and higher TNM stage (p &amp;lt;0.05). In vitro, reduced expression of SIK2 and SIK3 increases the proliferation of breast cancer cells. However, SIK2 and SIK3 had differential effects on breast cancer cell adhesion. Knockdown of SIK2 only enhanced the adhesion of triple negative breast cancer cells (MDA-MB-231), while knockdown of SIK3 decreased the adhesion of both MDA-MB-231 and MCF 7 cells. Knockdown of SIK1 and SIK3 increased the invasion of MDA-MB-231 cells (p&amp;lt;0.05). Knockdown SIK1 increased the barrier but knockdown of SIK2 and SIK3 decreased the barrier of the breast cancer cells (p&amp;lt;0.05). We also determined the effect of possible chemotherapeutic resistance in these cell lines: the cells were treated with various concentration of chemotherapy drugs and placebo and found that reduced SIKs increased the resistance of breast cancer cell to paclitaxel and cisplatin.Conclusion: In conclusion, we show that low expression of SIK1,2 and 3 in breast cancer was correlated with poor prognosis and chemotherapy resistance of breast cancer. Reduced SIKs promote tumour metastasis by enhancing tumour function and tight junction. SIKs could be potential biomarkers for prognosis and chemotherapy sensitivity in breast cancer. Citation Format: Ling Xin, Chang Liu, Yinhua Liu, Robert E. Mansel, Eleri Davies, Wen G. Jiang, Tracey A. Martin. Salt-inducible kinases suppress tumour function and regulate drug resistance in breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-41.

Coexpression of HOXA6 and PBX2 promotes metastasis in gastric cancer.

HOXA6 gene plays a role of the oncogene in various cancers. Nonetheless, its effect on gastric cancer (GC) occurrence and development is still unclear. We analysed whether HOXA6 interacts with the PBX2 protein using the STRING database. The molecular mechanism by which HOXA6 synergizes with PBX2 in GC metastasis is not fully understood. Here, we found that the expression of HOXA6 was increased in GC tissues and cell lines. The upregulation of HOXA6 was closely associated with differentiation, lymph node metastasis, AJCC stage, TNM stage, and poor survival outcome in GC patients based on tissue microarray (TMA) data. Moreover, the overexpression of HOXA6 promoted, whereas siRNA-mediated repression of HOXA6 inhibited, the cell proliferation, migration, and invasion of GC cells. Furthermore, HOXA6 could physically interact with and stabilize PBX2. In addition, HOXA6 and PBX2 expression was positively correlated in GC cells and tissue. HOXA6 and PBX2 suppression in GC cells also led to decreased migration and invasion potential in vitro. In vivo, HOXA6 was shown to cooperate with PBX2 to enhance cell metastasis via orthotopic implantation. These data indicate that HOXA6 promotes cell proliferation, migration, and invasion and that the HOXA6-PBX2 axis may be a useful biomarker for disease progression in GC.

The Interaction of GLUT1 and FOXM1 Leads to a Poor Prognosis in Colorectal Cancer.

Colorectal Cancer (CRC) is one of the most common fatal diseases with high morbidity. Alteration of glucose metabolism is one of the hallmarks in the development of CRC. Glucose Transporter 1 (GLUT1) is a key rate-limiting protein in hyperactive glucose metabolism and up-regulated in CRC, however, the underlying mechanism of the altered metabolism in CRC is still unknown. In this study, immunohistochemical staining was used to evaluate the expression of GLUT1 and FOXM1 in 135 paired CRC and adjacent normal tissues. The association between the expression of GLUT1/FOXM1 and clinicopathological factors was determined and the correlation between GLUT1 and FOXM1 in CRC was investigated. Our results revealed that regardless of tumor location, GLUT1 and FOXM1 were overexpressed in CRC tissues, especially in patients with positive lymph node metastasis and TNM stage III-IV. Furthermore, GLUT1 showed a significantly strong link with FOXM1 in CRC tissue. Overexpression of GLUT1 and FOXM1 may play critical roles in CRC leading to a poor prognosis.

MiR-369-3p inhibits tumorigenesis of hepatocellular carcinoma by binding to PAX6.

Accepted as crucial participators in human diseases, microRNAs (miRNAs) have been demonstrated to play important roles in cancer progression, including hepatocellular carcinoma (HCC). The purpose of this study is to preliminarily elucidate the role of miR-369-3p in HCC. Here, miR-369-3p and PAX6 expressions were detected by RT-qPCR. The functional mechanism of miR-369-3p/PAX6 axis was investigated by MTT, Transwell and luciferase reporter assays. The results showed that miR- 369-3p was downregulated in HCC and was associated with lymph node metastasis and TNM stage in HCC patients. Functionally, miR-369-3p overexpression inhibited cell viability and motility in HCC. Furthermore, PAX6 was confirmed as a direct target of miR-369-3p, and upregulation of PAX6 exerts carcinogenesis in the development of HCC. PAX6 can weaken the inhibitory effect of miR-369-3p in HCC. In conclusion, miR-369-3p inhibits the proliferation, migration and invasion of HCC cells by suppressing PAX6 expression.

Clinical significance of lncRNA MIR31HG in melanoma.

The aim of this study was to explore the expression of long non-coding RNA (lncRNA) MIR31HG in malignant melanoma (MM), and to investigate its clinical significance. The quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of lncRNA MIR31HG in MM tissues and cells. The relationship between lncRNA MIR31HG expression and the clinicopathological characteristics was analyzed. Furthermore, the cell counting kit-8 (CCK-8) and the transwell assays were performed to assess the effect of MIR31HG on cell proliferation and metastasis in vitro, respectively. The expression of MIR31HG was significantly upregulated in MM tissues and cells. To explore the relationship between MIR31HG expression and clinical features, the patients were divided into two groups according to the mean expression of MIR31HG, including high expression group and low expression group. The subsequent results indicated that MIR31HG expression was correlated with lymph nodes metastasis, distal metastasis, and TNM stage. The multivariate analysis indicated that a high expression of MIR31HG could be used as an independent prognostic factor for MM. MIR31HG low-expression cells were constructed in vitro. Compared with the control cells, the cells with low expression of MIR31HG showed significantly low malignancy, including decreased cell proliferation rate and migration and invasion rates. LncRNA MIR31HG was a novel factor involved in MM progression, which could be used as a potential biomarker and therapeutic target for MM.

Downregulation of miR-484 is associated with poor prognosis and tumor progression of gastric cancer

BackgroundGastric cancer is one of the most common cancers leading to high cancer mortality. MicroRNA-484 (miR-484) has been evaluated as a biomarker for various types of cancers. The subject of this study is to investigate the functional role of miR-484 in gastric cancer.MethodsThe expression of miR-484 in gastric cancer was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Kaplan-Meier survival and Cox regression analyses were employed to explore the prognostic significance of miR-484 in gastric cancer. The functional role of miR-484 in gastric cancer was determined by CCK-8 and Transwell assays.ResultsThe results showed that miR-484 was significantly downregulated in gastric cancer tissues and cell lines. The downregulation of miR-484 was closely related to differentiation, lymph node metastasis, TNM stage, and poor prognosis. Cox regression analyses demonstrated that miR-484 was an independent prognosis indicator for gastric cancer patients. Additionally, the downregulation of miR-484 enhanced cell proliferation, migration, and invasion in gastric cancer cells.ConclusionThese data demonstrated that miR-484 can serve as a potential prognostic biomarker and therapeutic target for gastric cancer and it may be involved in the progression of gastric cancer.

CCR6 promotes liver metastasis of colorectal cancer through epithelial-mesenchymal transition

Objective To detect the expressions of chemokine receptor 6 (CCR6), CC chemokine ligand 20 (CCL20) E-cadherin and vimentin in tissues of colorectal cancer and their paired liver metastases, and to investigate the possible mechanism of CCR6 in liver metastasis of colorectal cancer. Methods A total of 62 cases (54 cases of colon cancer and 8 cases of rectal cancer) of primary colorectal adenocarcinoma resection with wax lumps were selected from the First Hospital of Shanxi Medical University and Shanxi Oncology Hospital from 2009 to 2017 with complete data, including 20 samples of colorectal cancer resection with liver metastasis during the same period. The expressions of CCR6, CCL20, E-cadherin and vimentin in colorectal cancer and liver metastases tissues were detected by immunohistochemistry, and the relationships between the expressions of CCR6, E-cadherin and vimentin and the clinicopathological features of patients were analyzed. Logistic multivariate regression was used to analyze the relationship between liver metastasis and clinicopathological features, CCR6, E-cadherin and vimentin. Spearman correlation was used to analyze the correlations between CCR6 and E-cadherin and vimentin. Results The positive expression rate of CCR6 in colorectal cancer tissues was 66.1% (41/62), 85.0% (17/20) in colorectal cancer with liver metastasis and 70.0% (14/20) in liver metastasis tissues. The positive expression rate of CCL20 in colorectal cancer tissues was 83.9% (52/62), 90.0% (18/20) in colorectal cancer with liver metastasis and 90.0% (18/20) in liver metastasis tissues. The positive expression rate of E-cadherin in colorectal cancer tissues was 67.7% (42/62), 50.0% (10/20) in colorectal cancer with liver metastasis and 65.0% (13/20) in liver metastasis tissues. The positive expression rate of vimentin in colorectal cancer tissues was 79.0% (49/62), 85.0% (17/20) in colorectal cancer with liver metastasis and 90.0% (18/20) in liver metastasis tissues. The expression of CCR6 was closely related to lymph node metastasis (χ2=11.142, P=0.001), liver metastasis (χ2=4.694, P=0.030) and TNM stage (χ2=21.785, P 0.05). Logistic regression analysis showed that the expressions of CCR6 (OR=6.812, 95%CI: 1.206-38.474, P=0.030) and E-cadherin (OR=0.256, 95%CI: 0.069-0.945, P=0.041) were independent factors affecting the liver metastasis of colorectal cancer. Spearman correlation analysis showed that CCR6 was associated with E-cadherin expression (r=0.454, P=0.044) and vimentin expression (r=0.509, P=0.022) in 20 iver metastasis tissues of colorectal cancer. Conclusion CCR6 may promote colorectal cancer progress and liver metastasis by part of epithelial-mesenchymal transition. Key words: Colorectal neoplasms; Receptors, CCR6; Cadherins; Vimentin; Liver metastasis

Expression and clinical significance of ribosome-binding protein 1 in esophageal carcinoma

Objective To investigate the expression and clinical significance of ribosome-binding protein 1 (RRBP1) in esophageal carcinoma. Methods A total of 120 esophageal carcinoma patients admitted to Yulin First Hospital of Shaanxi Province from January 2010 to December 2014 were enrolled in this study. RRBP1 expression was detected in esophageal carcinoma and matched adjacent normal tissues by real-time quantitative PCR (qRT-PCR), Western blotting and immunohistochemical staining. The relationships of RRBP1 expression with clinicopathological futures and prognosis were statistically analyzed. Results RRBP1 expression level was significantly higher in esophageal carcinoma tissues compared with matched adjacent normal tissues. In the mRNA level, the relative quantitative expression in tumor tissues was 3.5±1.3, and 1.0±0.3 in adjacent normal tissues, with a significant difference (t=19.130, P<0.001). In the protein level, the relative quantitative expression in tumor tissues was 1.0±0.4, and 0.3±0.1 in adjacent normal tissues, with a significant difference (t=4.225, P<0.001). The immunohistochemical results showed that RRBP1 high expression was found in 71 (59.2%) tumor tissues, and the proportion dropped to 11.7% (14/120) in adjacent normal tissues, with a significant difference (χ2=59.182, P<0.001). In addition, RRBP1 expression was correlated with lymph node metastasis and TNM stage (χ2=10.631, P=0.001; χ2=31.212, P<0.001). Survival analysis revealed that RRBP1 expression, lymph node metastasis and TNM stage were significantly correlated with patients′ prognosis (χ2=9.455, P=0.006; χ2=14.542, P<0.001; χ2=11.987, P<0.001). Cox regression analysis showed that high expression of RRBP1 (RR=2.441, 95%CI: 1.267-4.702, P=0.008), lymph node metastasis (RR=4.024, 95%CI: 2.180-7.424, P<0.001) and high TNM stage (RR=3.054, 95%CI: 1.452-6.421, P=0.003) were the risk factors for poor prognosis of esophageal carcinoma patients. Conclusion RRBP1 is highly expressed in esophageal carcinoma and can serve as a potential biomarker to predict patients′ prognosis. Key words: Esophageal neoplasms; Prognosis; Survival analysis; Ribosome-binding protein 1

The expression and clinical significance of DDR2 and IFITM1 in nasopharyngeal carcinoma

Objective To investigate the expression of discoid domain receptor 2 (DDR2) and interferon-induced transmembrane protein 1 (IFITM1) in nasopharyngeal carcinoma (NPC) patients and their clinical significance. Methods From November 2014 to November 2015, 65 patients with nasopharyngeal carcinoma were selected. All patients underwent nasopharyngeal biopsy. All specimens were embedded in paraffin after biopsy. All specimens were confirmed by pathology. Another 65 rhinitis mucosa specimens with chronic inflammation confirmed by pathology in the same period were selected as control group. The clinical and pathological data of the two groups were collected. The mRNA and protein expression levels of DDR2 and IFITM1 in nasopharyngeal carcinoma tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry. The correlation between them was analyzed by Pearson. All patients were followed up for 3 years, and the 3-year survival period of the patients was analyzed by Kaplan-Meier method. Results The results of qRT-PCR showed that the relative expression levels of DDR2 and IFITM1 in nasopharyngeal carcinoma tissues were significantly higher than those in control group (P<0.05). Immunohistochemical results showed that the positive rates of DDR2 and IFITM1 in nasopharyngeal carcinoma were significantly higher than those in control group (P<0.05). The results of expressions of DDR2 and IFITM1 and the clinicopathological analysis of the patients showed that the expression of DDR2 was correlated with TNM stage, differentiation degree and infiltration depth, and IFITM1 was correlated with lymph node metastasis, TNM stage, differentiation degree and infiltration depth (P<0.05). Pearson correlation analysis showed that there was correlation between DDR2 and IFITM1 (r=0.608, P<0.01). Kaplan-Meier analysis showed that the progression-free survival rate (41.17%) and total survival rate (52.94%) in DDR2 negative expression group were significantly higher than those in positive expression group (16.67%, 18.75%, P<0.05). The progression-free survival rate (42.86%) and total survival rate (61.90%) in IFITM1 negative expression group were significantly higher than those in positive expression group (18.18%, 20.45%, P<0.05). Conclusions DDR2 and IFITM1 are highly expressed in nasopharyngeal carcinoma, which may be involved in the occurrence and development of nasopharyngeal carcinoma and significantly affect the prognosis of patients. Key words: Nasopharyngeal neoplasms; Discoidin domain receptor 2; Interferon-induced transmembrane protein 1

Expression of leptin protein in gastric cancer and its clinical significance

Objective To investigate the relationship between the expression of leptin protein and clinicopathological features and prognosis of gastric cancer. Methods The cancer tissue specimens of 112 patients diagnosed with gastric cancer in Shaanxi Provincial Cancer Hospital from January 2009 to December 2012 were collected. Random number table method was used to select 50 cases of paracancerous normal mucosa tissues as the controls. The expression of leptin protein was detected by using immunohistochemistry. And the relationship between the expression of lepin protein and the clinicopathological features and prognosis was analyzed. Results The positive rate of leptin protein in gastric cancer tissues was higher than that in paracancerous normal gastric mucosa tissues, and the difference was statistically significant [68.8% (77/112) vs. 34.0% (17/50), χ2 = 17.139, P < 0.01]. The expression of leptin protein was associated with tumor vessel invasion, invasion depth and TNM stage (all P < 0.05). The expression of leptin protein was positively correlated with tumor invasion depth and TNM stage (r = 0.265, P = 0.005; r = 0.318, P = 0.001). The 5-year total survival rates of patients with positive and negative expression of leptin protein were 65.2% and 78.4%, respectively, and the difference was statistically significant (χ 2 = 9.526, P = 0.002). The 5-year total survival rates of patients who received neoadjuvant chemotherapy or not were 71.7% and 67.6%, respectively, and the difference was not statistically significant (χ 2 = 2.321, P = 0.128). In patients with positive expression of leptin protein, 5-year total survival rates of patients who received neoadjuvant chemotherapy or not were 47.4% and 74.2%, respectively (χ 2 = 6.336, P = 0.012). In patients with negative expression of leptin protein, 5-year total survival rates of patients who received neoadjuvant chemotherapy or not were 92.3% and 18.2%, respectively (χ 2 = 14.237, P < 0.01). Cox multivariate regression analysis showed that leptin protein expression, lymph node metastasis, pathological grading, vessel invasion and TNM stage were independent prognostic factors for patients with gastric cancer (all P < 0.05). Conclusion Leptin protein is highly expressed in gastric cancer tissues, and it can be used as a marker for judging the prognosis and chemotherapy effect of gastric cancer patients. Key words: Gastric neoplasms; Leptin; Prognosis; Treatment outcome

Abstract 1644: Pancreatic cancer survival prediction using machine learning and comparing its performance with TNM staging system and prognostic nomograms

Abstract Background: Pancreatic cancer is one of the deadliest cancers with a 5-year survival rate of only 6%. Patients with cancer often want to know how long they have left to live and it’s the first question patients ask after diagnosis. Reliable predictions are very important for achieving more personalized care and better management. However, the accuracy of physicians' clinical predictions of survival is poor. Predicting pancreatic cancer survival is challenging due to different tumor characteristics, treatments and patient populations. In this study, we evaluate the performance of Machine Learning (ML) in survival prediction compared to TNM system and published nomograms. Methods: Pancreatic cancer patients were identified through the Surveillance, Epidemiology and End Results database (SEER). Clinical data of the patients were extracted including: age, sex, race, marital status, tumor site, tumor histology, grade, tumor size, extension, Lymph Node (L.N) involvement, metastasis, cancer sequence, TNM stage, surgery, radiotherapy, chemotherapy, examined (L.N), positive (L.N) and survival months. Patients’ records were randomly divided into a training set (80%) and a validation set (20%). ML algorithms were tested to predict survival at 6, 12 and 24 months as well as TNM staging system and two nomograms. Results: A total number of 22,700 patients were identified through SEER from 2004 – 2013 with median survival of 12 months. The most common primary sites were head of pancreas (62.8%), tail (13.2%), and body (10.7%). Random Forests algorithm achieved better results compared to other models. The trained model yielded Area under the Receiver Operating Characteristic Curve (AUCs) of 86.6% at 6 months, 83.4% at 12 months and 82.2% at 24 months. Compared to TNM staging system which achieved AUCs of 66.6% at 6 months, 65.5% at 12 months and 57% at 24 months. The nomograms achieved AUCs of 71.1% and 55.2% in predicting 1-year-survival. Sensitivity of the trained model were 80%, 75% and 79% at 6, 12 and 24 months, respectively. The most important characteristics which influenced the model prediction performance were: age at diagnosis, surgery and tumor size. Conclusion: Machine learning achieved a much better performance compared to TNM staging system and prognostic nomograms. Improved survival prediction can help in in making better treatment decisions and planning social and care needs. Citation Format: Mohamed H. Osman. Pancreatic cancer survival prediction using machine learning and comparing its performance with TNM staging system and prognostic nomograms [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1644.