Predictive Factor For Poor Prognosis Research Articles

Long non-coding RNA FENDRR inhibits NSCLC cell growth and aggressiveness by sponging miR-761.

The aim of this paper is to investigate the functions of long noncoding RNA (lncRNA) FOXF1 Adjacent Non-Coding Developmental Regulatory RNA (FENDRR) in the growth and aggressiveness of non-small cell lung cancer (NSCLC). The expression of FENDRR in NSCLC tissues and cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and colony formation assays were conducted to explore the roles of FENDRR on the growth of NSCLC cell. The wound healing and transwell invasion assays were conducted to explore the impact of FENDRR on NSCLC cell migration and invasion. The apoptosis of NSCLC cell was detected using flow cytometer-based Annexin V/Propidium Iodide (PI) dual staining. The xenograft model was conducted to investigate the effect of FENDRR on the growth of NSCLC cell in vivo. The expression of Ki67 was measured by immunohistochemical (IHC) staining using Ki67 antibody. Bioinformatics analysis and Luciferase reporter assay were applied to identify that miR-761 was the target of FENDRR. Additional, colony formation and transwell experiments were utilized to confirm that FENDRR inhibited the growth and aggressiveness of NSCLC cell by regulating miR-761. We found a marked down-regulation of FENDRR in NSCLC tissues compared to tumor-adjacent tissues. FENDRR down-expression was detected in four NSCLC cell lines (H1650, HCC827, H1975 and A549) compared to the human non-tumorigenic bronchial epithelial cell, BEAS-2B. Low expression of FENDRR was identified as a predictive factor for poor prognosis of patients with NSCLC. The over-regulation of FENDRR inhibited the proliferation, migration and invasion capacities of NSCLC cell and promoted the apoptosis of NSCLC cell in vitro whereas the down-regulation of FENDRR caused the opposite results. Moreover, the over-expression of FENDRR restrained the growth of NSCLC cell in vivo. We found that there were potential binding sites between FENDRR and miR-761 and the level of miR-761 was inversely associated with the expression of ENDRR in NSCLC tissues. Finally, the rescue experiments suggested that the anti-oncogenic role of FENDRR was at least partially mediated by miR-761 in NSCLC. We found that FENDRR was down-expressed in NSCLC and the over-expression of FENDRR inhibited the malignant phenotypes of NSCLC cell by binding to miR-761 competitively.

The prognostic significance of pretreatment serum γ-glutamyltranspeptidase in primary liver cancer: a meta-analysis and systematic review.

Aim: To assess the prognostic value of the pretreatment serum γ-glutamyltranspeptidase (GGT) level in patients with primary liver cancer (PLC). Methods: Relevant studies were systematically searched online on Web of Science, PubMed, and Embase databases published until 9 October 2018. The end points were overall survival (OS), recurrence-free survival (RFS), and disease-free survival (DFS). Meta-analysis was conducted using hazard ratio (HR), and its 95% confidence interval (CI) as effect measure. Results: A total of 33 eligible studies with 9238 patients with PLC were included in this meta-analysis. The synthesized analysis showed that that higher serum GGT level was significantly related to poorer OS (HR: 1.79, 95% CI: 1.66–1.93, P<0.01), RFS (HR: 1.60, 95% CI: 1.46–1.77, P<0.01), and DFS (HR: 1.52, 95% CI: 1.33–1.73, P<0.01) of patients with PLC. Subgroup analyses demonstrated that the negative prognostic impact of higher serum GGT level on OS and RFS was still of significance regardless of ethnicity, pathological type, sample size, cut-off value, first-line treatment, and analysis type. Conclusion: The pretreatment serum GGT might be a predictive factor of poor prognosis for PLC patients.

Predictive factors of overall survival in primary intracranial pure choriocarcinoma

The incidence of primary intracranial pure choriocarcinoma (PIPC) is extremely rare. Only several case and case series have been previously reported; therefore, there is still lack of knowledge about the prognosis and its standard treatment. We performed a collective study of all reported cases of PIPC to identify the predictive factors related with OS. A comprehensive search was performed on Pubmed’s electronic database using the terms “primary intracranial choriocarcinoma” and “malignant germ cell tumor”. Data about gender, various location, the presence of intratumoral hemorrhage, metastasis and treatment modalities were extracted from the published articles and we analyzed the overall survival based on this predictive factors. 51 cases were eligible and met the inclusion criteria. The majority of the patients were in the child population (44.7%) age between 6 and 12 years old. 77.1% of the patient were male and 22.9% were female. Tumor located other than suprasellar and pineal area showed better prognosis. Median OS of PIPC was 22 months. Patient underwent gross total resection had better outcomes compared with those who only had partial or subtotal resection. Adjuvant therapy (especially chemotherapy) significantly improved OS (p = 0.000, log-rank test). PIPC is chemosensitive and metastasis is the predictive factor for poor prognosis.

Impact of tumor size on survival of patients with resected pancreatic ductal adenocarcinoma: a systematic review and meta-analysis

BackgroundThe impact of tumor size on prognosis for surgically treated patients with pancreatic ductal adenocarcinoma (PDAC) remains controversial. A systematic review and meta-analysis was performed to evaluate this issue.MethodsRelevant studies published from January 2000 to June 2017 were identified through EMBASE and PUBMED. Data were pooled for meta-analysis using Review Manager 5.3.ResultsTwenty eight observational studies involving a total of 23,945 patients were included. Tumors > 2 cm was associated with poor prognosis: the pooled hazard ratio (HR) estimate for overall survival was 1.52 (95% confidence interval [CI]: 1.41–1.64; P < 0.0001) by univariate analysis and 1.61 (95% CI: 1.35–1.91; P < 0.0001) by multivariate analysis; the pooled HR estimate for disease-free survival was 1.74 (95% CI: 1.46–2.07; P < 0.0001) by univariate analysis and 1.38 (95% CI: 1.12–1.68; P = 0.002) by multivariate analysis. When compared with patients with tumors ≤2 cm, those with the tumors > 2 cm had higher incidences of lymph node metastasis, poor tumor differentiation, lymph vessel invasion, vascular invasion, perineural invasion, and positive intraoperative peritoneal cytology.ConclusionThese data demonstrate that PDAC size > 2 cm is an independent predictive factor for poor prognosis after surgical resection and associated with more aggressive tumor biology.

A case of Erdheim-Chester disease with spinal cord compression and sphenoid sinus involvement

Erdheim-Chester disease is a rare form of non-Langerhans cell histiocytosis. It is an inflammatory disorder associated with BRAF V600E mutation in 50% of cases. This multisystem disease is rarely associated with spinal involvement. Neurological involvement is an independent predictive factor of poor prognosis. The diagnosis is histopathological based on CD68-positive and CD1A-negative histiocytes. Treatment with interferon-alpha is an independent predictor of survival in Erdheim-Chester disease and vemurafenib has also been shown to be effective for BRAF V600E mutation. We report a clinical case of a 51-year-old patient with multiple and rare locations of Erdheim-Chester disease, particularly at the sphenoid sinus.

Glycemic variability determined with a continuous glucose monitoring system can predict prognosis after acute coronary syndrome

BackgroundImpaired glucose metabolism is an established risk factor for coronary artery disease. Previous studies revealed that glycemic variability (GV) is also important for glucose metabolism in patients with acute coronary syndrome (ACS). We explored the association between GV and prognosis in patients with ACS.MethodsA total of 417 patients with ACS who received reperfusion wore a continuous glucose monitoring system (CGMS) in a stable phase after admission and were monitored for at least 24 consecutive h. The mean amplitude of glycemic excursion (MAGE) was calculated as a marker of GV. We divided into two groups based on the highest tertile levels of MAGE (MAGE = 52 mg/dl). The groups were followed up for a median of 39 months [IQR 24–50 months]. The primary endpoint was the incidence of major adverse cardiovascular and cerebrovascular events (MACCE).ResultDuring follow-up, 66 patients experienced MACCE (5 patients had cardiovascular death, 14 had recurrence of ACS, 27 had angina requiring revascularization, 8 had acute decompensated heart failure, and 16 had a stroke). MACCE was more frequently observed in the high MAGE group (23.5% vs. 11.6%, p = 0.002). In multivariate analysis, high MAGE was an independent predictive factor of poor prognosis for MACCE (odds ratio, 1.84; 95% confidence interval, 1.01–3.36; p = 0.045).ConclusionGlycemic variability determined with a CGMS is a predictor of prognosis in patients with ACS without severe DM.Trial registration UMIN 000010620. Registered April 1st 2012

Prognostic significance of CIP2A expression in solid tumors: A meta-analysis.

CIP2A, cancerous inhibitor of protein phosphatase 2A, was initially recognized as an oncoprotein. Recently several studies revealed that CIP2A could function as a prognosis biomarker, however, the result remained not comprehensive, partly due to small number of patients included individually. Here we carried out a meta-analysis of published studies to assess the prognostic significance of CIP2A in solid tumors. All eligible studies were identified through searching PubMed, Embase and Web of Science database. In this meta-analysis, 22 studies involving 4,579 participants were included, and we verified that CIP2A over-expression was significantly related with poor overall survival (pooled HR = 1.844, 95% CI = 1.528–2.225, P<0.001) and short disease free survival (pooled HR = 1.808, 95% CI = 1.591–2.055, P<0.001) in solid tumors. Additionally, subgroup analysis suggested that the trend of a poor overall survival with an increased CIP2A expression was present in East-Asian and European patients, as well as in lung cancer and colorectal cancer. To sum up, CIP2A over-expression was associated with poor survival in human solid tumors and might be a predictive factor of poor prognosis.

Clinical significance of matrix metalloproteinase-2 in endometrial cancer: A systematic review and meta-analysis.

Background:Matrix metalloproteinase-2 (MMP-2), a member of the zinc-dependent metalloproteinase gene family, plays a vital role in cancer invasion, metastasis, and progression. This systematic review and meta-analysis aims to explore the clinical significance of MMP-2 expression in endometrial cancer.Methods:PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure databases were systematically searched up to September 30, 2017, supplemented by manual searches of bibliographies. Two reviewers independently identified articles, extracted data, assessed quality, and cross-checked the results. Meta-analysis was conducted to explore the difference in the positive rate of MMP-2 expression between patients with endometrial cancer and those with endometriosis or normal endometrium, and to investigate the associations of MMP-2 expression with clinicopathologic characteristics of patients with endometrial cancer. Weighted mean differences and risk ratios (RRs) with 95% confidence interval (CI) were calculated for continuous and dichotomous variables, respectively.Results:Totally 20 studies were selected for this systematic review and meta-analysis. Compared with those with endometriosis or normal endometria, the positive rate of MMP-2 expression is significantly higher in patients with endometrial cancer (RR = 2.31, 95% CI: 1.78–3.00, P < .01). MMP-2 expression was significantly associated with Federation of Gynecology and Obstetrics stage (RR = 1.19, 95% CI: 1.09–1.31, P < .01), histologic grade (RR = 1.10, 95% CI: 1.01–1.19, P = .02), lymph node metastasis (RR = 1.32, 95% CI: 1.15–1.51, P < .01), and myometrial invasion (RR = 1.25, 95% CI: 1.12–1.38, P < .01).Conclusion:The results showed that MMP-2 was expressed in high percentage of endometrial cancer and its expression may be associated closely with clinical stage, and tumor invasion and metastasis, indicating that MMP-2 overexpression may serve as a predictive factor for poor prognosis of endometrial cancer.

High NUSAP1 expression predicts poor prognosis in colon cancer

Background and aimNucleolar and spindle-associated protein 1 (NUSAP1) is an indispensable mitotic regulator. Aberrant NUSAP1 expression is associated with perturbed mitosis and tumorigenesis. In this study, we investigated the clinical significance of NUSAP1 expression in colon cancer. Methods and materialsImmunohistochemical staining was performed to determine NUSAP1 protein levels in paraffin colon tumor specimens. Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was conducted to detect NUSAP1 mRNA levels in colon tumor samples. The association between NUSAP1 protein expression and clinicopathological characteristics of patients with colon cancer was assessed. A Kaplan-Meier analysis was performed to determine the prognostic significance of NUSAP1 in colon cancer. A Cox proportional hazards model was used to calculate univariate and multivariate hazard ratios for the NUSAP1 and other clinicopathological variables. ResultNUSAP1 protein and mRNA levels were significantly higher in colon tumor tissues than in paired non-cancerous adjacent tissues (P < 0.001, respectively). NUSAP1 protein expression was significantly correlated with histopathological grading (P < 0.001), depth of invasion (P = 0.001), lymph node metastasis (P < 0.001) and TNM stage (P < 0.001). The overall survival rate of patients with high NUSAP1 expression was significantly lower than for patients with low NUSAP1 expression (log-rank test, P < 0.001). A multivariate Cox model demonstrated that NUSAP1 is an independent risk factor for overall survival (P = 0.025). ConclusionNUSAP1 is overexpressed in colon cancer and high expression of NUSAP1 acts as an independent predictive factor for poor prognosis in colon cancer.

Loss of skeletal muscle mass after curative gastrectomy is a poor prognostic factor.

Sarcopenia has been reported to relate to poor prognosis in various malignant cancer types. The present study aimed to clarify the prognostic impact of skeletal muscle mass (SMM) loss after curative gastrectomy in patients with gastric cancer. A total of 119 patients who underwent curative gastrectomy for gastric cancer between 2009 and 2016 were analyzed. The SMM loss at 6 months postoperatively compared with the SMM prior to surgery was calculated using the hospital records. The median loss of SMM was 3.8%. Multivariate logistic regression analysis demonstrated that total gastrectomy was a significant and independent risk factor for SMM loss of ≥5% (odds ratio=2.58; P=0.02). Results from multivariate analysis using stepwise Cox proportional hazards regression indicated that the following factors were significantly associated with shorter overall survival after curative gastrectomy: Age [>70 years; hazard ratio (HR)=2.46, P=0.04], TNM stage (≥2; HR=2.65, P=0.04) and loss of SMM (≥5%; HR=2.57, P=0.03). The present findings suggested that loss of SMM after curative gastrectomy for gastric cancer is an independent predictive factor for poor prognosis.

Association between H3K4 methylation and cancer prognosis: A meta-analysis.

BackgroundHistone H3 lysine 4 methylation (H3K4 methylation), including mono‐methylation (H3K4me1), di‐methylation (H3K4me2), or tri‐methylation (H3K4me3), is one of the epigenetic modifications to histone proteins, which are related to the transcriptional activation of genes. H3K4 methylation has both tumor inhibiting and promoting effects, and the prognostic value of H3K4 methylation in cancer remains controversial. Therefore, we performed a systematic review and meta‐analysis to examine the association between H3K4 methylation and cancer prognosis.MethodsA comprehensive search of PubMed, Web of Science, ScienceDirect, Embase, and Ovid databases was conducted to identify studies investigating the association between H3K4 methylation and prognosis of patients with malignant tumors. The data and characteristics of each study were extracted, and the hazard ratio (HR) at a 95% confidence interval (CI) was calculated to estimate the effect.ResultsA total of 1474 patients in 10 studies were enrolled in this meta‐analysis. The pooled HR of 1.52 (95% CI 1.02–2.26) indicated that patients with a lower level of H3K4me2 expression were expected to have shorter overall survival, while the pooled HR of 0.45 (95% CI 0.27–0.74) indicated that patients with a lower level of H3K4me3 expression were expected to have longer overall survival.ConclusionThis meta‐analysis indicates that increased H3K4me3 expression and decreased H3K4me2 expression might be predictive factors of poor prognosis in cancer. Further large cohort studies are needed to confirm these findings.

MicroRNA-1296 Facilitates Proliferation, Migration And Invasion Of Colorectal Cancer Cells By Targeting SFPQ.

MicroRNAs (miRNAs) are involved in cancer genesis and progression via acting as tumor suppressors or oncogenes. Previous studies report that miR-1296 shows upregulation in both colorectal cancer (CRC) tissues and plasma samples. However, the accurate clinical significance of miR-1296 and its role in CRC have not been well investigated. The aim of the present study was to disclose the aberrant expression, clinical significance, and the relevant biological function of miR-1296 in CRC. We found a marked upregulation of miR-1296 expression in CRC tissues compared to tumor-adjacent tissues. MiR-1296 overexpression was detected in five CRC cell lines (HCT116, Caco2, HT29, SW620 and SW480). High miR-1296 level was remarkably correlated with tumor size (>5cm), lymph node metastasis and TNM stage (III+IV). Notably. High miR-1296 expression was identified as a predictive factor for poor prognosis of CRC patients by survival analysis. MiR-1296 knockdown inhibited proliferation, migration, invasion capacities of HCT116 and SW480 cells in vitro. Moreover, miR-1296 silencing restrained the growth of CRC cells in vivo. Splicing factor proline and glutamine rich (SFPQ), a novel RNA binding protein, was identified as a direct target gene of miR-1296 in CRC. Downregulation of SFPQ expression was inversely associated with miR-1296 expression in CRC tissues. The Cancer Genome Atlas (TCGA) data revealed the prognostic value of dysregulated SFPQ in CRC patients. Interestingly, our findings established that the oncogenic role of miR-1296 was at least partially mediated by SFPQ in CRC cells. Collectively, these data indicate that miR-1296 accelerates CRC progression possibly by targeting SFPQ and may serve as a potential predictive factor and therapeutic target for CRC.

Pentraxin 3 overexpression accelerated tumor metastasis and indicated poor prognosis in hepatocellular carcinoma via driving epithelial-mesenchymal transition.

As a pattern recognition receptor, pentraxin 3 (PTX3) has been found to exert the pleiotropic roles on a variety of cancers. However, the accurate clinical significance of PTX3 in hepatocellular carcinoma (HCC) has not been well defined. The aim of the present investigation was to determine the expression characteristics, prognostic significance, and the relevant biological effect of PTX3 in HCC. The expression of PTX3 was evaluated in tumor and adjacent liver tissues from 210 HCC patients using immunohistochemistry staining. And it was found that a marked up-regulation in the expression of PTX3 in the HCC specimens, which was remarkably correlated with high serum AFP level (P = 0.006), larger tumor size (P <0.001), liver cirrhosis (P = 0.004), advanced TNM stage (P = 0.022), PVTT (P = 0.010), intra-hepatic metastases (P = 0.019), and MVI (P <0.001). PTX3 was identified as an independent predictive factor of poor prognosis by multivariate analysis. Ectopic expression of PTX3 enhanced proliferation, migration, invasion capacities of Huh7 cells and induced EMT phenotype. Silencing PTX3 obtained the opposite results. Moreover, the in vivo experiments confirmed PTX3 induced EMT and promoted proliferation and growth of HCC cells. Collectivelly, these data indicated that PTX3 could accelerate HCC progression through activating EMT and served as a potential predictive factor and therapeutic target for HCC.

High Serum CA19-9 Concentration Predicts Poor Prognosis in Elderly Patients with Stage IV Colorectal Cancer

Background/Aim: The optimal treatment strategy for elderly patients with stage IV colorectal cancer (CRC) remains controversial due to limited research data. The purpose of this study was to evaluate treatment results and to clarify the prognostic factors, especially poor prognosis factors, in elderly patients with stage IV CRC. Methods: We retrospectively reviewed the data of 82 elderly patients (aged ≥75 years) with stage IV CRC who underwent surgical treatment at our hospital between April 2001 and March 2017. Factors that affected prognosis and the ability to undergo treatment were analyzed via multivariate analysis. Results: The median overall survival (OS) in the patients with high pretreatment serum carbohydrate antigen 19-9 (CA19-9) concentration (> 370 U/mL) was significantly worse than in those with lower serum CA19-9 concentration (0–370 U/mL) (8.5 vs. 19.2 months, p = 0.0059). In univariate analysis, age (≥80 years) (p = 0.014), performance status of 1–3 (p = 0.028), and high pretreatment serum CA19-9 concentration (p = 0.014) were significant prognostic factors for poor OS. By contrast, resection of the primary tumor (p = 0.024), chemotherapy (p < 0.0001), and resection of distant metastasis (p = 0.0005) were significant prognostic factors for favorable OS. Multivariate analysis showed that a high pretreatment serum CA19-9 concentration was an independent prognostic factor for poor OS (p = 0.01). Meanwhile, resection of the primary tumor (p = 0.033), chemotherapy (p < 0.0001), and resection of distant metastasis (p = 0.0008) were prognostic factors for favorable OS. Conclusions: A high pretreatment serum CA19-9 concentration (> 370 U/mL) was a reliable predictive factor for poor prognosis, and aggressive treatments should be performed carefully in these patients. Moreover, various treatments, including surgery and chemotherapy, might improve OS in elderly patients with stage IV CRC.

Assessment of BAALC Gene Expression in Acute Myeloid Leukemia Patients Compared to Control Group in North-East of Iran

Acute myeloid leukemia (AML) is recognized as one of the most common types of leukemia among adults. This condition is characterized by the uncontrolled proliferation of myeloid progenitors, affecting the normal function of different systems in the human body. Various factors such as genetic abnormalities, exposure to chemicals, and viruses can induce AML. Expression of NPM1, CEBPA, MN1, and BAALC genes is among important genetic factors affecting AML prognosis and diagnosis. The aim of this study was to assess amount of BAALC gene expression in AML patients and its relation to survival rate. This case-control study was performed at Mashhad University of Medical Sciences, Mashhad, Iran. 56 AML patients and 56 healthy individuals were participated in this research. The level of BAALC gene expression was assessed by real-time polymerase chain reaction (RT-PCR) method; GPI gene was used as the control. For statistical analysis, SPSS version 21 was applied. P-value less than 0.05 was considered statistically significant. In total, 55.3 and 44.7 of the participants were male and female, respectively. BAALC gene up- and down-regulation was reported in 28.6 and 71.4 of AML cases, respectively. BAALC gene expression and hematological parameters were significantly different between the two groups (p< 0.05). Based on the findings, the survival rate was estimated at 31 and 39 months in patients with BAALC up- and down-regulation, respectively. BAALC gene over expression could be considered as a predictive factor for poor prognosis and reduced survival in AML patients. © 2017, UHOD - Uluslararasi Hematoloji Onkoloji Dergisi. All rights reserved.

Clinicopathological and prognostic significance of platelet count in patients with ovarian cancer

Aim: Increasing evidence indicates that platelet count is a useful biomarker of long-term outcomes in patients with ovarian cancer. However, the prognostic value of platelet count in patients with ovarian cancer remains controversial. We therefore conducted a meta-analysis aimed to investigate the prognostic role of the platelet count in patients with ovarian cancer.Method: A comprehensive search was performed from the databases of PubMed, Embase and the Cochrane Library until June 20, 2017. A total of 18 studies with 6754 patients were included. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) and odds ratios and 95% CIs from each study were pooled. Results: The results demonstrated that elevated pretreatment platelet count was significantly related to poor survival from ovarian cancer; the pooled HRs for overall, progression-free and disease-free survival were 1.81 (95% CI 1.52–2.15), 1.48 (95% CI 1.24–1.75) and 1.39 (95% CI 1.19–1.61), respectively. Subgroup analyses were divided by ethnicity, sample size, FIGO stage, cut-off value of the platelet count, analysis method and Newcastle Ottawa Scale score, but the results did not show any significant change in the main results. Increased platelet count was also significantly associated with the FIGO stage, tumor differentiation, ascites, residual tumor mass, CA125 level, recurrence and metastasis.Conclusion: This meta-analysis revealed that an elevated platelet count pretreatment denotes a predictive factor of poor prognosis and unfavorable clinicopathological parameters for ovarian cancer patients.

Increased copy number of mitochondrial DNA predicts poor prognosis of esophageal squamous cell carcinoma.

Change in mitochondrial DNA (mtDNA) copy number has been reported in esophageal squamous cell carcinoma (ESCC). However, its prognostic implication in ESCC remains largely unknown. Using reverse transcription-quantitative PCR assay, the mtDNA copy number was assessed in a cohort of patients with ESCC (n=141) and normal esophageal tissues (n=45), and the association between variable mtDNA levels and clinical outcomes of patients with ESCC were studied. Data revealed that ESCC patients exhibited an increased mtDNA content compared to control subjects. Furthermore, increased mtDNA content was associated with a significantly increased risk of cancer-associated mortality. This molecular event was associated with poorer survival in patients with ESCC, and was an independent predictor of patient survival. Data demonstrated that increased mtDNA content is a common genetic event in ESCC and may be a predictive factor of poor prognosis for ESCC patients.

PBX3 is associated with proliferation and poor prognosis in patients with cervical cancer.

Pre-B-cell leukemia homeobox 3 (PBX3) is upregulated in various malignancies; however, the role of PBX3 in cervical cancer (CC) is unknown. The purpose of this study was to explore the expression characteristics, clinicopathological significance, and molecular biological function of PBX3 in CC. The expression levels of PBX3 were analyzed in CC cell lines and tumor specimens by real-time polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemical staining. The clinicopathological characteristics associated with PBX3 expression were evaluated. An RNA interference approach was employed to suppress PBX3 expression in CC in vitro and in vivo, determine its role in cell proliferation and analyze its molecular function. We found that PBX3 expression was significantly upregulated in CC cell lines and clinical specimens compared with normal cells and adjacent nontumorous cervical tissues. PBX3 was an independent predictive factor of poor prognosis, and its expression was correlated with tumor diameter, pathological grading, lymph node metastasis, invasion depth, vascular invasion, and clinical stage of CC. Multivariate analysis suggested that PBX3 expression may represent an independent prognostic indicator of the survival of CC patients. CC patients with high PBX3 expression exhibited reduced overall survival compared with those with low PBX3 expression. Additionally, stable downregulation of PBX3 expression in CC cell lines suppressed cell proliferation and decreased p-AKT protein expression levels in vitro. Similarly, in vivo assays demonstrated that PBX3 downregulation in CC cells markedly inhibited tumor size and weight. Overall, we demonstrated that PBX3 can promote CC cell proliferation via the AKT signaling pathway and that it may serve as a prognostic marker. Our data indicate that inactivation of PBX3 may be an effective clinical treatment for CC.

Impact of the histological phenotype of extrahepatic bile duct carcinoma.

The classification of histological phenotypes was originally conceived for pancreatic intraductal papillary mucinous neoplasms. Recently, it has been introduced for extrahepatic cholangiocarcinoma. The aim of the present study was to clarify the associations between histological phenotype and clinicopathological features of extrahepatic cholangiocarcinoma, using 99 cases of surgically-resected extrahepatic cholangiocarcinoma. All cases were divided into one of two histological phenotypes: Biliary-type (BT; 56 cases, 56.6%) or metaplastic-type (MT; 43 cases, 43.4%). The clinicopathological features were compared between these two phenotypes. BT tumors exhibited significantly poorer differentiation, more frequent lymph node metastasis (BT vs. MT, 42.9 vs. 30.2%; P=0.042), more severe venous invasion (v2-3: BT vs. MT, 64.3 vs. 23.3%; P<0.001), and more severe perineural invasion (ne2-3: BT vs. MT, 78.6 vs. 48.8%, P=0.002). Furthermore, the overall (P=0.015) and disease-free (P=0.003) survival times were significantly decreased in patients with BT vs. MT tumors. In conclusion, extrahepatic cholangiocarcinoma with a BT phenotype has greater malignant potential, and may be an important predictive factor for poor prognosis.

High expression of eIF3d is associated with poor prognosis in patients with gastric cancer.

BackgroundEukaryotic initiation factor 3 subunit d (eIF3d) is the largest subunit of eIF3, which is shown to promote protein synthesis in cancer cells. Increased expression of eIF3d has been shown in some types of cancers, but has not been previously studied in gastric cancer (GC). Thus, the aim of this study was to analyze eIF3d expression in GC.Patients and methodsExpression of eIF3d was detected by immunohistochemistry in GC tissues and adjacent noncancerous (ANC) tissues. Samples were obtained from 210 patients with GC who had received curative gastrectomy. Clinicopathological features and survival rate were also analyzed.ResultsExpression rates of eIF3d in GC and ANC were 45.2% and 21.0%, respectively. High expression of eIF3d protein was significantly related to tumor stage, as determined by lymph node metastasis and depth of invasion (p<0.05). The Kaplan–Meier survival curves showed that patients with high eIF3d expression had a significantly poor overall survival (p=0.005). Multivariate Cox regression analyses showed that the level of eIF3d was an independent predictive factor of poor prognosis for GC (p=0.017).ConclusionExpression of eIF3d was upregulated in GC. High expression of eIF3d was determined as an independent poor prognostic factor in GC. It is suggested that eIF3d could be a good biomarker in GC.