Advanced Tumor Node Metastasis Stage Research Articles

Prognostic significance of preoperative IKBKE expression in esophageal squamous cell carcinoma.

PurposeIκB kinase epsilon (IKBKE; IKKε), a member of the nuclear factor-κB kinase inhibitor family, is upregulated in several human cancers, including breast cancer, prostate cancer, and ovarian cancer. Esophageal squamous cell carcinoma (ESCC) is one of the most common and most aggressively malignant cancers with dismal prognosis. However, the state of IKBKE expression in ESCC is still unknown and its potential value remains unexplored.Patients and methodsIKBKE protein expression was evaluated by immunohistochemistry in 118 paraffin specimens of ESCC treated by curative surgery. All patients were regularly followed up by telephone over 3 years after surgery. The chi-square test, Kaplan–Meier method, and Cox proportional hazard regression model were used to analyze the relationship of IKBKE expression, clinicopathological characteristics, and prognostic value for ESCC.ResultsIKBKE expression was 61.9% (73/118) in paraffin-embedded archived ESCC. Its expression was significantly associated with tumor differentiation grade (p=0.045) and advanced TNM (pathologic tumor node metastasis) stages (p=0.023). In univariate analysis, IKBKE expression was closely associated with decreased 3-year disease-free survival (HR 1.804, 95% CI 1.076–3.027; p=0.023) and overall survival (HR 2.118, 95% CI 1.189–3.773; p=0.009). Meanwhile, in multivariate analysis it was identified as an independent prognostic factor for 3-year disease-free survival (HR 1.777, 95% CI 1.034–3.054; p=0.037) and overall survival (HR 2.078, 95% CI 1.138–3.796; p=0.017).ConclusionOur data indicated for the first time that IKKε expression is a highly recurrent event in ESCC and could play a pivotal role in the evaluation of prognosis. IKBKE upregulation is negatively associated with disease-free survival and overall survival. Therefore, IKBKE could serve as a prognostic variable and potential therapeutic target for this malignancy.

MicroRNA-125a-5p inhibits invasion and metastasis of gastric cancer cells by targeting BRMS1 expression.

Accumulating studies have demonstrated microRNAs (miRNAs/miRs) have an important role in multiple processes of human malignant tumor development and progression. Decreased expression of miR-125a-5p has been observed in several types of cancer, including gastric cancer (GC). However, the mechanism and exact function of miR-125a-5p in GC have not been largely elucidated. In the present study, reverse transcription-quantitative polymerase chain reaction indicated that the expression of miR-125a-5p was downregulated in GC tissues and cell lines compared with matched normal tissues (P<0.01) and normal gastric mucosa cell lines (P<0.01), respectively. Moreover, clinical pathological characteristics and Kaplan-Meier analysis indicated that a low expression of miR-125a-5p was not only associated with lymph metastasis, peritoneal dissemination and advanced tumor-node metastasis stage but also affected the prognosis of GC patients. Compared with miR-control-transfected GC cells, markedly decreased migration and invasion was observed in GC cells that overexpress miR-125a-5p. By contrast, increased metastasis and invasion were observed in miR-125a-5p-knocked down cells compared with the control. Furthermore, luciferase reporter assays indicated that breast cancer metastasis suppressor 1 (BRMS1) was a direct target of miR-125a-5p. Notably, a positive correlation between the levels of BRMS1 and miR-125a-5p in GC tissues was observed, and BRMS1 expression was indicated to be regulated by miR-125a-5p in GC cells. In conclusion, miR-125a-5p may act as a tumor suppressor by targeting the metastasis-inhibitory gene, BRMS1. The data suggesting that BRMS1 is a potential target gene of miR-125a-5p, may provide novel insight into miRNA regulation of human gene expression, and a useful target for gene therapy of GC.

Clinical significance of programmed death-1 ligand-1 expression in patients with non-small cell lung cancer: a 5-year-follow-up study.

The programmed death-1-ligand 1 (PD-L1) has been recently suggested to play a pivotal role in the immune evasion of tumors from host immune system. In the study, we tried to reveal the clinical significance of PD-L1 in patients with non-small cell lung cancer (NSCLC), which is one of the most aggressive and intractable malignant tumors. PD-L1 expression in 120 NSCLC tissue specimens and 10 benign control samples embedded with wax were retrospectively detected by immunohistochemistry. No PD-L1 was detected in the 10 benign controls, whereas 57.5% of NSCLC tissue specimens showed PD-L1 expression. There was no relationship between PD-L1 expression and patient age, gender or histopathological type. However, PD-L1 expression was significantly correlated to the degree of tumor cell differentiation, stage of tumor node metastasis (TNM) and patient survival. Poor tumor cell differentiation and advanced TNM stage were related to higher PD-L1 expression. PD-L1-negative NSCLC patients had longer overall 5-year survival than PD-L1-positive patients ( P <0.0001). PD-L1 status was a significant independent prognostic factor of NSCLC (χ2 = 18.153, RR = 2.946, P <0.001). Up-regulated PD-L1 expression in NSCLC is related to the degree of tumor cell differentiation and TNM stage. PD-L1 status may be a new predictor of prognosis for patients with NSCLC.

Dihydropyrimidine dehydrogenase predicts survival and response to interferon-\u03b1 in hepatocellular carcinoma

Metastasis and recurrence contribute to poor prognosis of hepatocellular carcinoma (HCC). Recently, we reported that interferon-α (IFN-α) can suppress metastasis of HCC; however, the underlying mechanism has not been fully described. In this study, we demonstrated that expression of dihydropyrimidine dehydrogenase (DPYD), a pyrimidine catabolic enzyme, was dose-dependently downregulated by IFN-α in HCC tissues from nude mice. Notably, DPYD expression was found to be significantly increased in HCC cell lines with higher metastatic potentials compared with their controls. Moreover, upregulation of DPYD in HCC cells could promote in vitro migration, invasion, and in vivo lung metastasis, and inducing changes characteristic of epithelial-mesenchymal transition (EMT). In contrast, knockdown of DPYD inhibited these processes. Mechanistically, DPYD functioned as a positive regulator of EMT in HCC by targeting the p38/NF-κB/Snail1 pathway. Clinically, tissue microarray analysis showed that high DPYD expression was positively associated with aggressive tumor characteristics, including larger tumor size, tumor recurrence, and advanced tumor node metastasis (TNM) stage, and independently correlated with poorer overall survival times after curative resection. HCC patients with low DPYD expression have better response to IFN-α therapy. Taken together, our findings elucidate that IFN-α could downregulate DPYD expression to inhibit EMT and HCC metastasis, and suggest that DPYD might be a potential prognostic biomarker and a therapeutic target for HCC.

Clinical Effect of Adjuvant Cytokine-Induced Killer Cells Immunotherapy in Patients with Stage II-IVB Nasopharyngeal Carcinoma after Chemoradiotherapy: A propensity score analysis.

As an adjuvant immunotherapy, cytokine-induced killer cells (CIKs) infusion has been demonstrated to exert potent effectiveness in several types of cancer patients who received curative treatment. However, controversy exists regarding whether nasopharyngeal carcinoma (NPC) patients can benefit from additional treatment after radical radiotherapy or chemoradiotherapy to improve their distant control and survival. In this retrospective study, we aimed to evaluate the efficacy of adjuvant CIK cells therapy in NPC patients with stage II-IVB after curative treatment. From January 1, 2005 to December 31, 2012, 85 pairs of NPC patients matching by propensity score matching (PSM) method to balance prognostic factors were included in this study: 85 cases underwent radical treatment, 85 cases received radical treatment and sequential CIKs infusion. We found that disease-free survival (DFS) and overall survival (OS) were significantly better in the CIK group than that in the control group (P = 0.009, P < 0.001, respectively). Adjuvant CIK cells immunotherapy was showed to be an independent prognostic factor for survival of the patients in further multivariate analysis. In subgroup analyses, the DFS and OS of patients with T3/4, III and IV A-B TNM (tumor-node-metastasis) stages were significantly enhanced in CIK group compared to control group. Nevertheless, both NPC patients with high and low EBV DNA benefited from adjuvant CIK cells immunotherapy. In conclusion, CIKs infusion is an effective adjuvant immunotherapy for enhancing the prognosis of NPC patients who have received the standard treatment, particularly for those with more aggressive tumor (T3/4) or advanced TNM stage.

Analysis of IMP3 expression in primary tumor and stromal cells in patients with colorectal cancer.

Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is an oncofetal protein upregulated in tumor cells during carcinogenesis. The aim of the present study was to investigate the expression status of IMP3 in colorectal cancer (CRC) tissues and its clinical significance. Immunostaining was performed in 130 CRC samples, the association of IMP3 expression with clinicopathological characteristics was assessed and 58 patients were selected for survival analysis. To the best of our knowledge, the present study describes for the first time the expression of IMP3 in tumor stromal components of CRC. Stromal expression of IMP3 was detected in 24/130 (18.5%) CRC tissue specimens and was associated with tumor-node-metastasis (TNM) stage (stage III–IV, P=0.003), lymph node metastasis (P=0.006), lympho-vascular invasion (P=0.003), tumor border (P=0.013). Tumoral expression of IMP3 was detected in 94/130 (72.3%) of CRC specimens and was associated with T classification (T3-T4, P=0.027), tumor-node-metastasis (TNM) stage (stage III–IV, P=0.011), lymph node metastasis (P=0.048), tumor budding (>10 buds, P=0.005). Further study indicated that patients with IMP3 expressed in tumor cells and tumor stroma tend to have poorer overall survival rates (P=0.02 and P=0.06, respectively). Moreover, tumoral expression of IMP3 and TNM stage were identified to be independent prognostic factors in CRC. IMP3 was not only expressed in tumor cells but also in stroma cells. Stromal expression of IMP3 was associated with lymph node metastasis and advanced tumor TNM stage. Moreover, the survival analysis indicated that there is a significant association between IMP3 expression in tumor cells and a poorer overall survival rate in patients with CRC. The expression of IMP3 maybe a predicted factor for CRC patient.

Overexpression of MPC1 inhibits the proliferation, migration, invasion, and stem cell-like properties of gastric cancer cells.

Invasion and metastasis are major malignant characteristics of human gastric cancer (GC), but the molecular mechanisms underlying the invasion and metastasis of GC cells remain elusive. MPC1, a key factor that controls pyruvate transportation through the inner mitochondrial membrane, was reported to be downregulated and correlated with poor prognosis in several cancers. However, the effects of MPC1 on human GC have not been illustrated. In this study, we investigated the potential role of MPC1 in the proliferation, migration, invasion, and stem cell-like properties of human GC cells and evaluated its prognostic significance for patients with GC. We found that MPC1 protein and mRNA levels were significantly decreased in GC tissues and cell lines. Low MPC1 expression was associated with tumor T stage, N stage, and advanced tumor node metastasis stage. Decreased MPC1 expression was an independent prognostic marker and correlated with poor overall survival of patients with GC. Furthermore, overexpression of MPC1 inhibited the proliferation, migration, invasion, and stem cell-like properties of GC cells. These findings suggest that MPC1 may be a novel prognostic marker and a potential therapeutic target in human GC.

Overexpression of long non-coding RNA colon cancer-associated transcript 2 is associated with advanced tumor progression and poor prognosis in patients with colorectal cancer.

The aim of the present study was to explore the clinicopathological and prognostic significance of long non-coding RNA (lncRNA) colon cancer-associated transcript 2 (CCAT2) expression in human colorectal cancer (CRC). Expression levels of lncRNA CCAT2 in CRC, adjacent non-tumor and healthy colon mucosa tissues were detected by quantitative polymerase chain reaction. The disease-free survival and overall survival rates were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using Cox proportional hazard analysis. The expression level of lncRNA CCAT2 in CRC tissues was increased significantly compared with adjacent normal tissues or non-cancerous tissues. CCAT2 expression was observed to be progressively increased between tumor-node-metastasis (TNM) stages I and IV. A high level of CCAT2 expression was revealed to be associated with poor cell differentiation, deeper tumor infiltration, lymph node metastasis, distance metastasis, vascular invasion and advanced TNM stage. Compared with patients with low levels of CCAT2 expression, patients with high levels of CCAT2 expression had shorter disease-free survival and overall survival times. Multivariate analyses indicated that high CCAT2 expression was an independent poor prognostic factor. Therefore, increased lncRNA CCAT2 expression maybe a potential diagnostic biomarker for CRC, and an independent predictor of prognosis in patients with CRC.

Application and Indication of Carcinoembryonic Antigen Triggered 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Scanning in the Detection of Relapse of Colorectal Cancer Patients After Curative Therapy

This study aimed to explore the characteristics of patients with colorectal cancer (CRC) following curative therapy that may benefit from fluorine-18-2-uoro-2-deoxy-D-glucose positron emission tomography/computed tomography (F-FDG PET/CT) scanning, evaluate the application of carcinoembryonic antigen (CEA)-triggered F-FDG PET/CT scanning, and provide referential indicators. This retrospective study included 56 CRC patients who received a PET/CT scan as a primary examination because of rising CEA levels after curative therapy and who had not received any other radiological examinations previously. The rate of recurrence or metastasis was 75.0% by PET/CT scan but was 69.6% with follow-up treatment. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 94.9%, 70.6%, 87.5%, 88.1%, and 85.7%, respectively. TNM (tumor, node, metastasis) stage, body mass index, and CEA level were significant prognostic factors. Positron emission tomography/CT can be selectively applied as a primary examination in CRC patients with asymptomatic elevation of CEA. High CEA levels, increased body mass index, and advanced TNM staging are risk factors for relapse.

Elevated serum DAND5 is associated with metastasis and predicts poor prognosis in colorectal cancer.

The biologic and clinical significance of DAND5 remains unknown in colorectal cancer (CRC). Herein, we investigated the function of DAND5 and evaluated its clinical significance in both serum and matched primary tumors in patients with CRC. The role of DAND5 was explored in CRC cells and clinical significance of DAND5 was investigated in CRC patients (n = 217) and healthy controls (n = 63). Knockdown of DAND5 significantly decreased CRC cell proliferation, migration and invasion partly associated with epithelial-mesenchymal transition phenotype. Serum DAND5 levels in CRC were significantly higher than in normal controls and accurately distinguished CRC from healthy subjects. High serum DAND5 levels were significantly correlated with tumor differentiation, large tumor size, advanced Tumor Node Metastasis (TNM) stage, lymph node and liver metastasis, high carcinoembryonic antigen level, recurrence, poor overall and disease-free survival. Serum DAND5 level, together with lymph node metastasis, were independent prognostic factors for CRC patients. High DAND5 protein expression in CRC tissues was increased according to TNM stage. A significant positive correlation existed between serum DAND5 levels and matched DAND5 expression in CRC tissues. Our data provide novel evidence for the clinical significance of DAND5 as a potential biomarker for CRC prognosis.

SIX4 promotes metastasis via activation of the PI3K-AKT pathway in colorectal cancer.

BackgroundSeveral studies report aberrant expression of sine oculis homeobox (SIX) homolog family members during cancer development and progression. SIX4 participates in organ development, such as myogenesis and neurogenesis. However, the expression and clinical implication of SIX4 in colorectal cancer (CRC) remains unclear.MethodsThe SIX4 expression levels in colorectal patients were assessed in nine different human cancer arrays and compared using patient survival data. SIX4 expression was silenced in two cell culture lines for invasion and wound healing assessment. Finally, bioinformatics assessments ascertained the pathways impacted by SIX4.ResultsSIX4 was upregulated in The Cancer Genome Atlas CRC cohort and other gene expression omnibus (GEO) cohorts. In addition, SIX4 expression significantly correlated with lymph node metastasis and advanced Tumor Node Metastasis (TNM) stages. Moreover, SIX4 overexpression was related to unfavorable prognosis in CRC patients. Silencing SIX4 inhibited CRC cell metastasis by surpressing AKT phosphorylation.DiscussionSIX4 is upregulated in CRC and can be used as a prognosis biomarker.

Serum long non-coding RNAs MALAT1, AFAP1-AS1 and AL359062 as diagnostic and prognostic biomarkers for nasopharyngeal carcinoma.

Circulating RNAs in serum, plasma or other body liquid have emerged as useful and highly promising biomarkers for noninvasive diagnostic application. Herein, we aimed to establish a serum long non-coding RNAs (lncRNAs) signature for diagnosing nasopharyngeal carcinoma (NPC). In this study, we recruited a cohort of 101 NPC patients, 20 patients with chronic nasopharyngitis (CN), 20 EBV carriers (EC) and 101 healthy controls. qRT-PCR was performed with NPC cells and serum samples to screen a pool of 38 NPC-related lncRNAs obtained from the LncRNADisease database. A profile of three circulating lncRNAs (MALAT1, AFAP1-AS1 and AL359062) was established for NPC diagnosis. By Receiver Operating Characteristic (ROC) curve analysis, this three-lncRNA signature showed high accuracy in discriminating NPC from healthy controls (AUC = 0.918), CN (AUC = 0.893) or EC (AUC = 0.877). Furthermore, high levels of these three lncRNAs were closely related to advanced NPC tumor node metastasis stages and EBV infection. Serum levels of these three lncRNAs declined significantly in patients after therapy. Our present study indicates that circulating MALAT1, AFAP1-AS1 and AL359062 may represent novel serum biomarkers for NPC diagnosis and prognostic prediction after treatment.

Dynamic monitoring of circulating microRNAs as a predictive biomarker for the diagnosis and recurrence of papillary thyroid carcinoma.

Circulating microRNAs (miRNAs/miRs) are considered to be potential biomarkers for numerous types of cancer. However, previous investigations into the expression of miRNAs in the serum of patients with papillary thyroid carcinoma (PTC) to predict diagnosis, prognosis and recurrence have reported conflicting results, and the role of miRNAs remains unclear. The present study dynamically assessed the circulating miRNA profile in patients with PTC and determined whether miRNAs in the serum could be used as biomarkers for the diagnosis, prognosis and recurrence of PTC. The expression levels of 3 reportedly upregulated miRNAs (miR-222, miR-221 and miR-146b) were analyzed using reverse transcription-quantitative polymerase chain reaction in 106 patients with PTC, 35 patients with benign thyroid nodules (BTN) and 40 paired controls. Patients with either newly diagnosed PTC or BTN who were undergoing thyroidectomies were recruited for a dynamic analysis of preoperative and postoperative serum miRNA levels. The results indicated that the expression levels of serum miR-222, miR-221 and miR-146b were significantly increased in patients with newly diagnosed PTC compared with controls and patients with BTN. Receiver operating characteristic curve analysis indicated that these miRNAs had a high diagnostic sensitivity and specificity for PTC prior to surgery. The expression of these three miRNAs in serum was significantly associated with poorer prognostic variables, including extrathyroidal invasion, metastatic lymph nodes and high-risk or advanced tumor node metastasis stage. More notably, the present study identified 2.36-, 2.69- and 5.39-fold reductions in the serum levels of miR-222, miR-221 and miR-146b, respectively, subsequent to patients undergoing a thyroidectomy. In addition, miR-222, miR-221 and miR-146b were overexpressed in the PTC with recurrence group compared with the PTC without recurrence group. Collectively, dynamic monitoring of circulating miRNAs may serve as a non-invasive biomarker for the diagnosis of PTC and the postoperative monitoring of its progression and recurrence.

Associations between body mass index and lymph node metastases of patients with papillary thyroid cancer: A retrospective study.

Epidemiological studies suggest that obesity is a risk of thyroid cancer, especially papillary thyroid cancer (PTC). However, the associations of obesity and clinic–pathological features, especially the association of body mass index (BMI) and lymph node metastasis of thyroid cancer are unclear. Seven hundred ninety-six primary patients with PTC were enrolled in this retrospective cohort study. The relationships between BMI and clinic-pathological features of PTC were evaluated by logistic regression models based on the 5-point increase in BMI and BMI quartiles (underweight, normal weight, overweight, and obesity). The 5-point increase in BMI was strongly associated with extra-thyroidal invasion [odds ratio (OR) 2.201, P < 0.001], primary tumor size larger than 1 cm (OR 1.267, P = 0.027), advanced tumor node metastasis (TNM) staging (OR 1.479, P = 0.004), and multifocality (OR 1.31, P = 0.01) in multivariable-adjusted models. The relationships between BMI and lymph node metastasis of PTC were evaluated by Mann–Whitney U test. The mean number of positive central lymph nodes and lateral nodes were increased with the increase of BMI when BMI ≥18.5 kg/m2. It was not shown in underweight group. The present study found that increased BMI was associated with the lymph node metastases (LNMs) of patients with PTC, and other invasive features, including large tumor size, extra-thyroidal invasion, advanced TNM staging, and multifocality. Further studies with long-term follow-up are needed to confirm this finding.

Ubiquitin ligase SMURF1 functions as a prognostic marker and promotes growth and metastasis of clear cell renal cell carcinoma.

Smad ubiquitin regulatory factor 1 (SMURF1), a recently identified E3 ubiquitin ligase, targets substrate proteins for ubiquitination and proteasomal degradation. Previous studies have reported that SMURF1 also functions as an oncogene in human cancers. However, the clinical value of SMURF1 and its role in clear cell renal cell carcinoma (ccRCC) are unknown. SMURF1 expression was analyzed in 100 cases of ccRCC and matched tumor‐adjacent specimens. SMURF1 was prominently overexpressed in ccRCC specimens compared with tumor‐adjacent specimens. Increased levels of SMURF1 were also observed in ccRCC cell lines. Clinicopathological detection verified that SMURF1 expression was associated with advanced tumor node metastasis stage, large tumor size and vascular invasion of ccRCC patients. Moreover, Kaplan–Meier analysis found that SMURF1 elevation led to adverse overall survival and disease‐free survival. Multivariate Cox regression analysis revealed that SMURF1 expression was an independent marker for prognosis prediction. Further experiments illustrated that SMURF1 knockdown significantly inhibited growth and metastasis of 769P cells, while SMURF1 overexpression promoted proliferation, migration and invasion in OSRC‐2 cells. Mechanistically, SMURF1 inversely regulated the expression of DAB2 interacting protein, which negatively mediated the activation of both the ERK/RSK1 and PI3K/AKT/mTOR pathways in ccRCC cells. Taken together, these results suggest that SMURF1 might be a promising biomarker and target for novel treatment of human ccRCC.

Actin-like protein 6A is a novel prognostic indicator promoting invasion and metastasis in osteosarcoma

Osteosarcoma harbors highly metastatic properties, accounting for postoperative recurrence and metastasis. Actin-like protein 6A(ACTL6A) regulates cell proliferation, migration and differentiation. However, the biologic role of ACTL6A in osteosarcoma remains unknown. In this study, the results showed that, by analysis of frozen fresh primary tumor tissues, matched non-cancerous bone tissues(NCBTs) and biopsy lung metastatic nodule tissues from 30osteosarcoma patients after radical surgical resection, ACTL6A was overexpressed in osteosarcoma tissues compared with matched NCBTs, and its expression level was associated with osteosarcoma metastasis. Immunohistochemical analyses of osteosarcoma tissue samples from two independent cohorts of formaldehyde-fixed, paraffin-embedded osteosarcoma tissue samples from total of 186osteosarcoma patients showed that high ACTL6A expression correlated with malignant clinicopathological features such as larger tumor size, high Ennecking grade, high histologic grade, and advanced tumor node metastasis stage. High ACTL6A expression was associated with poor prognosis for patients with osteosarcoma, and an independent and significant risk factor for disease-free survival and overall survival after radical tumor resection. Both invitro and invivo assays showed that ACTL6A overexpression promoted osteosarcoma cell invasion and metastasis, whereas knockdown of ACTL6A expression reduced osteosarcoma cell malignant behavior such as invasion and metastasis. Furthermore, we proved that ACTL6A promoted osteosarcoma cells of metastasis through facilitating epithelial-mesenchymal transition(EMT). Inconclusion, data from the present study demonstrated that ACTL6A was associated with poor survival and promoted osteosarcoma cell metastasis through EMT, suggesting that ACTL6A may be a novel prognostic biomarker and therapeutic target for osteosarcoma.

Therapeutic Outcomes of Patients with Multifocal Papillary Thyroid Microcarcinomas and Larger Tumors.

A retrospective review of 626 patients with multifocal papillary thyroid carcinoma (PTC) including 147 patients (23.5%) with multifocal papillary thyroid microcarcinoma (PTMC) from a total of 2,536 patients with PTC who visited the Chang Gung Medical Center in Linkou, Taiwan, was performed. A comparison of the clinical features between 626 multifocal and 1,910 solitary PTC cases showed that patients in the multifocal PTC group were older and had a smaller mean tumor size, a more advanced tumor-node-metastasis (TNM) stage, and a higher percentage of nonremission status compared to patients in the solitary PTC group. Of the 626 patients with multifocal PTC, the group with larger tumors showed a more advanced TNM stage, a higher percentage of lymph node metastasis and soft tissue invasion, and a higher nonremission rate compared to the multifocal PTMC group. Of the 626 patients with multifocal PTC, 25 patients (4%) died during a mean follow-up period of 7.1 ± 5.3 years. Kaplan-Meier survival curves showed a significantly lower survival rate associated with multifocal PTMC compared to that with solitary PTMC.

Predictive value of serum gamma-glutamyltransferase levels in patients with hepatocellular carcinoma.

Here we assessed the predictive value of gamma-glutamyltransferase (γ-GT) for the prognosis of patients with HCC and compared the γ-GT with other prognostic factors. We retrospectively analyzed outcomes for 858 patients first diagnosed with HCC. Cox univariate and multivariate analyses receiver operating characteristic (ROC) curve were used for the study of significance of prognostic factor. A Kaplan-Meier survival analysis was performed to assess the value of γ-GT as an HCC prognostic factor in different classifications of Barcelona Clinic Liver Cancer (BCLC) or Tumor Node Metastasis (TNM) and different levels of serum alpha fetoprotein (AFP). We showed patient survival rates were significantly associated with γ-GT as well as serum biological markers including absolute neutrophil count (ANC), absolute lymphocyte count (ALC), AFP. A γ-GT ≥ 75 U/L strongly indicated poor prognosis for HCC patients. The survival time of patients with γ-GT ≥ 75 U/L was significantly shorter in advanced BCLC and TNM stages and at any serum AFP level. All these results suggested that baseline γ-GT could effectively aid in determining the prognosis of patients with HCC, and the prognostic value of γ-GT ≥ 75 U/L was superior to that of Child-Pugh class, MELD stage, and serum AFP.

Retraction Note to: Overexpression of interleukins IL-17 and IL-8 with poor prognosis in colorectal cancer induces metastasis.

Current evidences indicated that a group of soluble mediators called chemokines is involved in tumor growth and metastasis. The association of IL-8 with tumor cell migration was previously found, and its expression was related to angiogenesis, tumor progression, and metastasis in many kinds of carcinomas in human and animal models. Furthermore, it has been showed that IL-17 plays its role as either a proteome of tumor progression or antitumor indifferent cancer models. To investigate the messenger RNA (mRNA) expressions of IL-8 and IL-17 in patients with colorectal cancer (CRC) and non-tumor tissue, quantitative real-time PCR was used in the study. Our results showed that expression of IL-8 mRNA was significantly increased in tumor tissues (mean ± SD 3.84 ± 0.08) compared with adjacent normal mucosa (mean ± SD 1.17 ± 0.75, P = 0.001). Furthermore, a higher expression of IL-17 mRNA was found in tumor tissues (mean ± SD 2.73 ± 0.69) when compared with normal tissues (mean ± SD 1.06 ± 0.07, P = 0.001). Our findings indicated that advanced tumor-node-metastasis (TNM) stage (P = 0.024) and histological grade (poorly differentiated, P = 0.013) and distant metastasis (P = 0.001) were correlated with expression of IL-8. Moreover, high expression of IL-17 showed significant association with early stage CRC (TNM) (P = 0.038). In conclusion, the expression of IL-8 and IL-17 mRNAs was significantly increased in tumor tissues compared with adjacent normal tissues. We found that advanced TNM stage and histological grade and distant metastasis were correlated with expression of IL-8, while high expression of IL-17 showed significant association with early stage CRC (TNM) stage and overexpression of IL-8 may be associated with progression of CRC.

CXCL1 gene silencing inhibits HGC803 cell migration and invasion and acts as an independent prognostic factor for poor survival in gastric cancer.

Chemokine (C-X-C motif) ligand 1 (CXCL1) is essential in oncogenesis and development of malignant tumors. The present study aimed to investigate CXCL1 expression in promoting lymph node metastasis in gastric cancer patients. Human gastric cancer cell lines were employed to detect CXCL1 expression. HGC803 cell migration and cell invasion were detected using a wound healing assay and Transwell invasion assay, respectively. A total of 100 patients who underwent radical gastric resection with lymph node dissection in the First Affiliated Hospital of Sun Yat-Sen University (Guangzhou, China) between 2007 and 2008 were included. Expression of CXCL1 and lymphatic vessel density (LMVD) was determined by using immunohistochemistry (IHC), and their association with clinicopathological features and prognosis was investigated. Cox survival regression analysis was used to analyze overall survival of patients. Results indicated that CXCL1 protein was expressed in all of investigated gastric cancer cell lines. Silencing of the CXCL1 gene reduced migratory and invasive ability of HGC803 cells. CXCL1 protein expression was detected by IHC in 41 patients (41%), these were associated with advanced tumor-node-metastasis (TNM) stage, LMVD, tumor differentiation and poor survival. LMVD was positively correlated with advanced TNM stage, size of tumor, tumor differentiation and poor survival rate. Furthermore, it was observed that TNM stage, tumor differentiation and CXCL1 were independent prognostic factors in the Cox survival regression analysis. Silencing of the CXCL1 gene inhibits HGC803 cell migration and invasion. The positive expression of CXCL1 is correlated with poor survival of gastric cancer patients and CXCL1 is an independent prognostic factor for gastric cancer.