Worse Tumor Differentiation Research Articles

The clinicopathological significance and prognostic value of PD-L1 in oral squamous cell carcinoma.

To investigate the relationship between the expression of PD-L1 in OSCC and the clinicopathological features and prognosis of patients. We retrospectively analyzed the clinicopathological data and prognosis of 381 OSCC patients. Immunohistochemical staining was performed on OSCC tumor specimens, and the expression level of PD-L1 was evaluated according to the combined positive score (CPS). Kaplan-Meier analysis was used to identify the effect of PD-L1 expression and clinicopathological features on the prognosis of patients. Univariate and multivariate Cox regression analyses were conducted to determine the hazard factors affecting the prognosis of patients. PD-L1 overexpression was significantly associated with cervical lymph node metastasis (p = 0.018), worse clinical stage (p = 0.022), worse tumor differentiation (p = 0.046), and worse depth of invasion (DOI) (p = 0.003). Poorer clinical stage and degree of tumor differentiation were significantly associated with poorer OS and DSS in patients. PD-L1 expression was not associated with prognosis in patients with OSCC. High PD-L1 expression was significantly associated with higher tumor malignancy in OSCC patients. Poorer clinical stage and degree of tumor differentiation were associated with poor prognosis in OSCC patients. Our results may help clinicians develop more appropriate individualized treatment strategies for their patients, thus improving their outcomes.

Prognostic significance of long noncoding RNA TTN-AS1 in various malignancies.

Increasing evidence has demonstrated that high TTN-AS1 expression is highly related to poor prognosis in diverse human cancers. However, the findings concerning the prognostic value of TTN-AS1 were inconsistent, as these conclusions were usually drawn with relatively small sample sizes. Hence, this meta-analysis proposes to investigate the prognostic significance of TTN-AS1 in multiple malignancies systematically. Web of Science, Springer, Embase, PubMed, Cochrane Library, and Scopus databases were comprehensively searched to retrieve studies related to the TTN-AS1 expression with the prognosis of malignancies. The significance of the TTN-AS1 in cancers was estimated by hazard ratios (HRs) or odds ratios (ORs). Additionally, the Gene Expression Profiling Interactive Analysis (GEPIA) analysis tool was used to strengthen our results further. Twenty studies involving 17 different cancers and 1330 patients were recruited into this meta-analysis. The research revealed that high TTN-AS1 expression was remarkably associated with unfavorable overall survival (OS) (HR = 2.07, 95%CI [1.78, 2.41], p < .00001) when compared with low TTN-AS1 expression in malignancies. Additionally, elevated TTN-AS1 expression significantly contributed to lymph node metastasis (OR = 4.09, 95%CI [3.08, 5.44], p < .0001), larger tumor size (OR = 2.42, 95%CI [1.56, 3.77], p < .0001), worse tumor differentiation (OR = 0.36, 95%CI [0.22, 0.59], p < .0001) and more advanced tumor stage (OR = 0.29, 95%CI [0.22, 0.38], p < .0001) with low or no heterogeneity existing. Moreover, high TTN-AS1 expression was connected with worse disease-free survival in five different cancers based on the GEPIA online database. The results of this meta-analysis support that high TTN-AS1 expression significantly correlates with worse prognosis in various cancers. Therefore, TTN-AS1 may be considered as a novel biomarker for malignancies.

Prognostic value of nicotinamide N-methyltransferase in human cancers: Evidence from a meta-analysis and database validation.

BackgroundPrevious studies indicated that dysregulated expression of nicotinamide N-methyltransferase (NNMT) contributed to the tumor progression and predicted poor prognosis in various cancers. However, there was no exact conclusion on account of the contradictory results across studies.MethodsThe relevant studies up to December 7, 2020 were searched in PubMed, Web of Science, and Embase. The association between NNMT expression and prognostic outcomes was explored, including overall survival (OS), disease-free survival (DFS), and clinicopathological features. The bioinformatics database was used to validate the findings.ResultsThirteen retrospective studies containing 2,591 patients with cancers were included in this analysis. High NNMT expression was significantly associated with shorter OS (hazard ratio [HR] = 2.01, 95% confidence interval [CI] = 1.42–2.86, and P < 0.01) and DFS (HR = 1.59, 95% CI = 1.23–2.05, and P < 0.01) compared to low NNMT expression in cancers. Compared to patients with low NNMT expression, patients with high NNMT expression tended to have worse tumor differentiation (P = 0.03), earlier lymph node metastasis (P = 0.01), earlier distant metastasis (P = 0.02), and more advanced clinical stage (P < 0.01).ConclusionHigh NNMT expression is an unfavorable factor of various cancers. NNMT is a promising indicator to predict the prognosis of various cancers and can serve as a potential therapeutic target in various cancers.

HOXC10 Promotes Metastasis in Colorectal Cancer by Recruiting Myeloid-derived Suppressor Cells.

Background: Since metastasis is the primary cause of death in human colorectal cancer (CRC) patients, the exact mechanism underlying CRC metastasis remains unclear. Here, we provide evidence for a unique function of HomeoboxC10 (HOXC10) in driving CRC metastasis, as well as treatment options for these subpopulation patients.Methods: Immunohistochemistry detected the expression of HOXC10 in the human CRC cohort. The function of HOXC10 in CRC metastasis was investigated using the cecum orthotopic model.Results: In CRC patients, elevated expression of HOXC10 expression was linked to lymph node metastases, distant metastasis, worse tumor differentiation, higher AJCC stage, and poor prognosis. HOXC10 is also an independent predictive predictor for CRC patients (P<0.001). HOXC10 overexpression increased the metastasis ability of MC38 cells and promoted the infiltration of MDSCs by upregulating CXCL5 at the same time. The CXCR2 inhibitor can reduce the rate of metastasis in MC38 cells by reducing MDSCs infiltration. SB225002, a CXCR2 inhibitor, and anti-programmed death-ligand 1 (anti-PD-L1) can significantly prevent CRC metastasis.Conclusions: HOXC10 overexpression upregulated CXCL5, which promoted MDSCs infiltration. Interrupting this loop might be a potential therapy option for HOXC10-induced CRC metastasis.

P-L12 Exploring Pathological Signatures for Predicting Recurrence of Early-stage Hepatocellular Carcinoma Based on Deep Learning

Abstract Background Early-stage hepatocellular carcinoma (HCC) is the ideal indication for liver resection. High recurrence rate limits the radical possibility. Current clinicopathological determinants are insufficient to reliably evaluate the recurrence risk after surgery. To address this global issue, we aimed to use deep learning to explore novel pathological signatures based on histological slides for predicting early-stage HCC recurrence and to evaluate the relationship between histological features and multi-omics information. Methods 576 pathological images collected from 547 patients with BCLC stage 0-A HCC who underwent hepatectomy from 2006 to 2015 were randomly divided into the training cohort and validation cohort. The external validation cohort was composed of 147 TNM I patients from TCGA database. Weakly supervised convolutional neural networks were used to identify six classes of HCC tissues. Pathological signatures were extracted and two novel risk scores were constructed by LASSO Cox to predict recurrence. The forecast performance of the scores and patients' prognosis were evaluated. The relationship between histological score (HS) and immune infiltrating cells was estimated by clustering analysis. Results The classification accuracy of HCC tissue was 94.17%. The C-indexes of histological score in the training, validation and TCGA cohorts were 0.804, 0.739 and 0.708, respectively. Multivariate analysis showed that microvascular invasion (HR = 1.46, 95% CI: 1.09-1.95) and HS (HR = 4.05, 95% CI: 3.40-4.84) were independent risk factors for recurrence-free survival. Patients in HS high-risk group had elevated alpha fetoprotein, worse tumor differentiation and higher proportion of microvascular invasion. HS was positively correlated with the expression of CD14 in adjacent normal liver tissue (P = 0.013), and negatively correlated with the expression of CD8 in tumor (P &amp;lt; 0.001). Conclusions This study established and validated two novel risk scores based on the histological slides using deep learning. HS performed well in recurrence prediction for early-stage HCC patients and indication of important clinicopathological features.

Prognostic significance of the expression of metastasis-associated in colon cancer-1 in gynecologic cancers and breast cancer: A protocol for systematic review and meta-analysis.

Background:The prognostic role of the expression of metastasis-associated in colon cancer-1 (MACC1) in gynecologic cancers and breast cancer remains unclear. The aim of this systematic review and meta-analysis was to determine the prognostic significance of MACC1 expression in gynecologic cancers and breast cancer.Materials and methods:PubMed, Web of Science and Embase were comprehensively searched up to February 9, 2020. Studies focusing on the relationship between the expression of MACC1 and prognosis in gynecologic cancers and breast cancer were included into the analysis. Pooled hazard ratio (HR) or odd ratio with 95% confidence interval (CI) was used to estimate the prognostic value of the expression of MACC1.Results:A total of 1,811patients with gynecologic cancers or breast cancer were included into the analysis. Patients with high expression of MACC1 tended to suffer a shorter overall survival (HR = 2.76, 95%CI = 2.12–3.59, P < .01) and recurrence-free survival (HR = 2.37, 95%CI = 1.44–3.90, P < .01) compared to those with low expression of MACC1. High expression of MACC1 was significantly associated with worse tumor differentiation (P = .04), more advanced FIGO stage (P < .01) and earlier lymph node metastasis (P < .01) compared to low expression of MACC1.Conclusion:Compared to low expression of MACC1, high expression of MACC1 predicts a worse prognosis of gynecologic cancers and breast cancer. The expression of MACC1 can serve as a prognostic indicator of gynecologic cancers and breast cancer.

Ampullary neuroendocrine tumors: A window into a rare tumor using a national database.

373 Background: Ampullary neuroendocrine tumors (NET) make up &lt; 1% of all gastrointestinal NETs. Information about their behavior and prognosis is reliant on small case series. This study set out to describe the population of patients who are diagnosed with ampullary NETs and compare them to patients with duodenal and pancreatic head NETs. Methods: The National Cancer Database (2004 – 2016) was queried for patients with ampullary, duodenal, and pancreatic head NETs. Clinicopathologic and treatment characteristics were compared. Subset analysis was performed on patients who underwent surgery. Kaplan Meier (KM) analysis and Cox regression were used to analyze the survival of patients with ampullary NETs. Results: Overall, 872 patients were identified with ampullary NET, 9692 with duodenal NET, and 6562 with pancreatic head NET. Patients with ampullary NET had an average age of 60.9 +/- 14.5 years, were evenly split among men and women (N = 437, 50.1% vs N = 435, 49.9%, respectively), and primarily Caucasian (N = 663, 76.0%). 72.1% underwent local tumor destruction or surgery (N = 629). Most did not receive radiation (N = 832, 95.4%), chemotherapy (N = 627, 71.9%), or hormone therapy (N = 788, 90.4%). Patients with ampullary NETs had more poorly differentiated tumors (N = 119, 13.6%) than patients with duodenal (N = 159, 1.6%) or pancreatic head (N = 602, 9.2%) NETs. Patients with ampullary NETs had more positive lymph nodes (N = 288, 33%) than patients with duodenal (N = 915, 9.4%) or pancreatic head (N = 1381, 21%) NETs. At five years, the overall survival for patients with ampullary, duodenal, and pancreatic head NETs was 57%, 68%, and 46%, respectively. Within the surgical population, five-year survival for patients with ampullary (N = 367), duodenal (N = 991), and pancreatic head (N = 1961) NETs was 60%, 74%, and 72%, respectively. When compared, there was a statistically significant difference between the mean overall survival of patients with ampullary (98 +/- 4.7 months), duodenal (112 +/- 2.5 months), and pancreatic head (108 +/- 1.7 months) NETs (p &lt; 0.001). In the cox regression analysis, sex, Charlson-Deyo score, lymph node positivity, lymph-vascular invasion, mitotic rate, chromogranin A level, 5-HIAA level, and tumor size did not correlate with survival. Increasing age (HR 1.04, CI 1.01 – 1.07, p = 0.008) and worse tumor differentiation (poorly differentiated HR 3.33, CI 1.38 – 8.04, p = 0.008 and undifferentiated HR 8.31, CI 2.77 – 24.92, p &lt; 0.001 compared to well differentiated) were associated with increased mortality. Conclusions: This study sheds light on a rare tumor histology. When compared to patients who underwent surgical resection for duodenal or pancreatic head NETs, patients with ampullary NETs had a significantly worse prognosis. Identifying prognostic factors allows us to create more concrete treatment recommendations and provide patients with improved prognostic information.

LINC00473 functions as an oncogene and predicts poor prognosis in pancreatic cancer via the cAMP/β-catenin axis.

To investigate the expression and function of LINC00463 in pancreatic cancer (PC), and to demonstrate the relationship between LINC00473 expression and clinical pathological characteristics and prognosis of PC. Expressions of LINC00473 in PC tissues and cell lines were detected using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). LINC00473 siRNA was synthesized to knock down the LINC00473 expression in PANC-1 cells. Proliferation, invasion, and migration abilities of experimental cells were analyzed using cell counting kit-8 (CCK-8) assay and transwell assay, respectively. cAMP activity was detected and protein expression of β-catenin was measured to explain the underlying mechanism of LINC00473 in PC. The prognosis and clinical pathological features of PC patients were illustrated. LINC00473 was highly expressed in PC tissues and cells. Higher level of LINC00473 was relative with larger tumor size, worse tumor node metastasis (TNM) stage, worse tumor differentiation, higher rates of perineural invasion, and lymphatic invasion. Knockdown of LINC00473 significantly inhibited cell growth, invasion, and migration of PANC-1 cells. LINC00473 activated cAMP and then promoted the phosphorylation of β-catenin to promote the progression of PC. Furthermore, high expression of LINC00473 and β-catenin remarkedly indicated poor prognosis of PC patients. LINC00473 was upregulated in PC tissues and cells, indicating a poor prognosis and clinical pathological features of PC. It promoted PC progression via activating the cAMP/β-catenin axis, which provided a novel target for the prediction for PC diagnosis, biological therapy, and prognosis.

Longer Operating Time During Gastrectomy Has Adverse Effects on Short-Term Surgical Outcomes

BackgroundGastric cancer continues to be one of the malignant tumor types with high morbidity and mortality worldwide. Although remarkable improvements have been made to combat gastric cancer, surgery is still the first choice of treatment for gastric cancer. MethodsThis was a single-center and retrospective study. A total of 110 patients who underwent radical gastrectomy with D2 lymph node dissection between 2014 and 2017 were included in this study, and all patients were treated by the same medical staff. Based on the median operating time, patients were grouped into a long-time group (>180 min) and a short-time group (≤180 min). Influences of operating time on outcomes of patients in the short-term and long-term groups were analyzed. ResultsThe long-time group showed a higher incidence of postoperative complications compared with the short time group (P < 0.01) with a significant decrease in serum albumin and the prognostic nutritional index value. Moreover, a long operating time was often caused by the operating start time (P < 0.001), excision difficulty caused by lager tumor size (P < 0.001), worse tumor differentiation, and deeper tumor invasion (P < 0.05). However, length of operating time did not significantly influence overall survival of patients who underwent radical gastrectomy. ConclusionsThe results suggested that operating time might be an indicator of the incidence of postoperative complication and that several important variables, such as prognostic nutritional index, serum albumin, operating start time, and excision time, could be intervened in the perioperative period to help patients gain a better outcome after gastrectomy.

The prognostic value of long noncoding RNA Sox2ot expression in various cancers: A systematic review and meta-analysis

BackgroundSeveral investigations have explored the prognostic value of long noncoding RNA Sox2 overlapping transcript (lncRNA Sox2ot) expression in human cancers, however, with inconsistent results. The aim of this study was to evaluate the prognostic role of lncRNA Sox2ot expression in various cancers. MethodsPubMed, Web of Science, Embase, and Cochrane Library were comprehensively searched to retrieve relevant studies. The relationships between lncRNA Sox2ot expression and prognostic parameters were detected, including overall survival (OS), tumor differentiation, clinical stage, distant metastasis, lymph node metastasis and so on. ResultsA total of 10 studies involving 943 cancer patients were finally included into the study. High lncRNA Sox2ot expression was significantly related to shorter OS in cancers (HR = 2.06, 95%CI = 1.67–2.55, P < 0.01). The cancer patients with high lncRNA Sox2ot expression tended to have worse tumor differentiation (P = 0.04), advanced clinical stage (P < 0.01), earlier distant metastasis (P < 0.01), and earlier lymph node metastasis (P = 0.01) compared to those with low lncRNA Sox2ot expression. However, there was no distinct correlation between lncRNA Sox2ot expression and age (P = 0.87), gender (P = 0.48), tumor size (P = 0.08), or vascular invasion (P = 0.07). ConclusionHigh lncRNA Sox2ot expression was significantly associated with worse OS, advanced clinical stage, worse tumor differentiation, earlier distant metastasis, and earlier lymph node metastasis in various cancers. LncRNA Sox2ot expression might a promising prognostic factor in various cancers.

Prognostic value of fever grade combined with neutrophil percentage in hepatocellular carcinoma patients presenting fever as the initial manifestation.

BackgroundHepatocellular carcinoma (HCC) patients with fever as the initial presentation are extremely rare. Our aim was to investigate the clinical characteristics and prognosis of patients with this disease.Patients and methodsThe clinical features were analyzed in a retrospective study of 63 HCC patients with fever as the first manifestation and 300 HCC patients without fever as the control group.ResultsHCC patients with fever had a higher neutrophil percentage, larger tumor size, worse tumor differentiation, advanced Barcelona Clinic Liver Cancer stage, and more hilar lymph node metastasis than HCC patients without fever (all P<0.05). Compared with HCC patients without fever, patients presenting with fever had shorter overall survival (OS, median: 13 months, P<0.001) and time to recurrence (TTR, median: 7.5 months, P<0.001). In addition, HCC patients with fever also had shorter OS and TTR than those without fever in all clinical subgroups with aggressive features (all P<0.05). Multivariate analysis showed that neutrophil percentage >70%, fever grade ≥38.5°C, tumor size >5 cm, and hilar lymph node metastasis were independent factors for OS and TTR. A positive correlation was observed between body temperature and serum neutrophil percentage (r=0.527, P<0.001). Patients with a fever grade ≥38.5°C had more incomplete encapsulation and larger tumor size, while those with a neutrophil percentage >70% presented with more incomplete encapsulation, vascular invasion, and worse tumor differentiation. Patients with a fever grade ≥38.5°C combined with a neutrophil percentage >70% had worse OS and TTR than other groups.ConclusionHCC patients presenting with fever have poorer prognosis than those without fever; however, their prognosis could be improved by timely surgical intervention. Patients with a neutrophil percentage >70% and a fever grade ≥38.5°C represent a rare HCC subgroup with an extremely dismal outcome and more aggressive clinical course.

Clinicopathological Differences and Prognostic Value of Hypoxia-Inducible Factor-2α Expression for Gastric Cancer: Evidence From Meta-Analysis.

Published literatures have reported the relationship between hypoxic-inducible factor-2α (HIF-2α) expression and clinicopathological features in gastric cancer (GC), but the evaluated conclusions remain controversial.A meta-analysis was carried to examine the clinicopathological features and prognostic values of HIF-2α in patients with GC. Systematic detailed searches were performed to Pub Med, Cochrane Library, and EBSCO until to August 2015.Six studies (508 specimens) were included in this meta-analysis. HIF-2α-positive expression indicates an unfavorable prognosis value and advanced clinicopathological differences for the available patient dates with GC. Further multivariate meta-analysis revealed that HIF-2α-positive expression in gastric cancer associated with deeper tumor infiltration (OR = 3.08; 95%CI: 1.18–8.04), higher rates of lymphatic metastasis (OR = 3.26; 95%CI: 1.10–9.63), higher TNM stage (III+IV) (OR = 2.61; 95%CI: 1.40–4.84), and much lower 5-year overall survival (OR = 2.08; 95%CI: 1.21–3.58). Nevertheless, there is no association between HIF-2α-positive expression and worse tumor differentiation (OR = 2.03; 95%CI: 0.73–5.64). In addition, by this subgroup analysis, HIF-2α-positive expression associated with deeper tumor infiltration (OR = 3.81; 95%CI: 1.03–14.08), higher lymphatic metastasis (OR = 4.71; 95%CI: 1.08–20.50), higher TNM stage (OR = 3.21; 95%CI: 1.57–6.57), worse tumor differentiation (OR = 3.08; 95%CI: 1.51–6.31), and lower 5-year overall survival (OR = 2.34; 95%CI: 1.15–4.79).Our results indicate that HIF-2α overexpression can potently predict the poor prognosis and may be a potential therapeutic target for gastric carcinoma, according to the limited evidence. Meanwhile, further studies are needed to elucidate the accuracy of these results.

Prognostic Value and Clinicopathological Significance of p-stat3 Among Gastric Carcinoma Patients: A Systematic Review and Meta-Analysis.

The overexpression of phosphorylated signal transducer and activator of transcription 3 (p-stat3) was detected in a variety of human tumors. The published studies on p-stat3 expression among gastric carcinoma patients remain controversial.In order to clarify the prognosis value of p-stat3 with overall survival and its association with clinicopathological characteristics in gastric carcinoma, we performed a systematic review and meta-analysis.Eligible studies were retrieved by searching PubMed, Embase, Cochrane library, and Chinese biomedical literature service system databases.Studies described the association between p-stat3 expression and clinicopathological characteristics and overall survival in gastric carcinoma patients; p-stat3 expression was detected by immunohistochemistry (IHC).Odds ratio (OR) and hazard ratio (HR) were considered as a measure of evaluating the association in meta-analysis; I was used to assess the heterogeneity across studies; publication bias was assessed with funnel plot, Egger test, and Begg test.Twenty-three studies including 2872 patients which evaluated the p-stat3 expression by IHC in gastric carcinoma were included. The pooled HR (HR = 2.02, 95% CI: 1.49-2.73, P < 0.00001) indicated that the increased p-stat3 expression was significantly associated with poor overall survival. In addition, when we investigated the association between p-stat3 overexpression and clinicopathological characteristics of gastric carcinoma, we found that the increased p-stat3 expression was significantly associated with tumor differentiation (poorly vs well-moderately: OR = 3.70, 95% CI: 1.98-6.93, P < 0.0001) and lymph node metastasis (present vs absent: OR = 2.40, 95% CI: 1.28-4.50, P = 0.007).The different type of primary antibody was used; the assessment methods of p-stat3 positive expression were defined differently; the locations of p-stat3 expression were different; the method of extrapolating HR from Kaplan-Meier survival curves did seem to be less reliable than when HR was extracted directly from literatures; sample sizes, the age of patients, and the follow-up durations are different.In conclusion, our meta-analysis indicates that the increased p-stat3 expression may be not only predict poor prognosis, but also be associated with worse tumor differentiation and lymph node metastasis in patients with gastric carcinoma.

Lactate Dehydrogenase Is an Important Prognostic Indicator for Hepatocellular Carcinoma after Partial Hepatectomy

Preoperative serum lactate dehydrogenase (LDH) has been used as a prognostic indicator for patients with hepatocellular carcinoma (HCC) treated with sorafenib or undergoing transcatheter arterial chemoembolization, but its significance in predicting survival of HCC patients who received curative resection remains undefined. A total of 683 patients with histopathologically confirmed HCC were enrolled in this study. The prognostic significance of preoperative serum LDH was determined by Kaplan-Meier analysis and a Cox proportional hazards regression model. The association between the preoperative serum LDH and clinicopathological parameters was evaluated by the χ2 test or linear regression analysis when appropriate. Higher preoperative serum LDH level was associated with worse prognosis. In a multivariate Cox proportional hazards analysis, the preoperative serum LDH level could predict overall survival and recurrence independently. Higher preoperative serum LDH level is associated with the elevated serum alpha-fetoprotein, the presence of hepatitis B surface antigen, larger tumor size, the presence of macrovascular invasion, the advanced tumor–lymph node–metastasis stage, worse tumor differentiation, and Child-Pugh B. Preoperative serum LDH level was an inexpensive, simple, convenient, and routinely measured biomarker exhibiting a potential to select patients at high risk with poor clinical outcome for appropriate treatment strategies.

TP53 and CDKN2a mutations in never‐smoker oral tongue squamous cell carcinoma

To determine the incidence and clinical significance of TP53 and CDKN2a somatic mutations in never smokers with oral tongue squamous cell carcinoma (OTSCC). Case series. Fifty-one paraffin-embedded tumors from never smokers with OTSCC were obtained. p53 and p16 expression was determined by immunohistochemical (IHC) staining. Tumor DNA was amplified by polymerase chain reaction, and direct sequencing and mutation analysis was performed. Statistical relationships among p53 and p16 IHC findings, TP53 and CDKN2a mutation status, and clinicopathologic characteristics were determined. Univariate and multivariate Cox models for survival were performed. Sixteen tumors (31.4%) showed strong expression of p53 by IHC. There was no correlation between p53 status and clinicopathologic variables or survival outcomes. TP53 mutations were seen in 10 tumors (19.6%). Patients with TP53 mutations had higher tumor-node-metastasis (TNM) stage (P=0.049), worse tumor differentiation (P=0.025), earlier recurrence (P=0.024), and more often died from their disease (P=0.043) than those without mutations. Five tumors (9.8%) showed p16 positivity by IHC. There was no correlation between p16 status and clinicopathologic variables or survival. CDKN2a mutations were seen in four tumors (7.8%). Patients with CDKN2a mutations had earlier recurrence (P=0.019) and more often died from their disease (P=0.010) than those without mutations. Kaplan-Meier curves show worse disease-free survival (P=0.0162, P=0.0025) and overall survival (P=0.0095, P=0.0001) for TP53 and CDKN2a mutations, respectively. Multivariate analysis demonstrated that TP53 and CDKN2a mutations were independent predictors of disease-free survival (P=0.038 and P=0.039, respectively). TP53 and CDKN2a mutations in never-smoker OTSCC are associated with worse clinicopathologic characteristics and poorer survival outcomes. N/A.

Prognostic role of microRNA-21 in gastric cancer: a meta-analysis.

BackgroundMounting evidence shows that microRNAs may be useful as prognostic biomarkers of gastric cancer. The aim of this meta-analysis was to summarize the predictive role of miR-21 for survival in patients with gastric cancer and to verify the association between expression of miR-21 and clinical characteristics.Material/MethodsAll the eligible studies were searched by PubMed and EMBASE and clinical characteristics and survival results were extracted. Then a meta-analysis was carried out to clarify the prognostic role of the miR-21 expression in different subgroups.ResultsWe included 8 studies dealing with gastric cancer in this meta-analysis. For overall survival, the pooled hazard ratio of higher miR-21 expression in tumor tissue was 2.00 (95% CI: 1.39–2.88, P<0.01), which could significantly predict poorer survival in gastric cancer patients. Importantly, subgroup analysis suggested that higher expression of miR-21 correlated with tumor differentiation 0.42 (95% CI: 0.25–0.70 p<0.01), lymph node metastasis 6.39(95% CI: 3.11–13.14, P<0.01), and TNM stage 0.38 (95% CI: 0.21–0.67, P<0.01).ConclusionsThis meta-analysis indicates that miR-21 detection has a prognostic value in patients with gastric cancer. In addition, overexpression of miR-21 is associated with worse tumor differentiation, lymph node metastasis, and TNM stage.

Meta-analysis of immunohistochemical expression of hypoxia inducible factor-1α as a prognostic role in gastric cancer

To conduct a meta-analysis to evaluate the prognostic role of hypoxia inducible factor-1α (HIF-1α) expression in gastric cancer. The PubMed, EMBASE, and Web of Science databases were searched systematically for all articles published in English before August, 2013. Pooled effect was calculated from the available data to evaluate the association between HIF-1α expression and 5-year overall survival and tumor clinicopathological features in gastric cancer patients. Pooled odds ratios (ORs) with 95%CIs were calculated using either a fixed-effects or a random-effects model. Nine studies matched the selection criteria, which reported on 1103 subjects, 548 of whom had HIF-1α positive expression (50%). This meta-analysis indicated that HIF-1α positive expression in gastric cancer correlated with lower 5-year overall survival (OR = 0.36; 95%CI: 0.21-0.64), worse tumor differentiation (OR = 0.38; 95%CI: 0.23-0.64), deeper invasion (OR = 0.42; 95%CI: 0.32-0.57), higher rates of lymph node metastasis (OR = 2.23; 95%CI: 1.46-3.40), lymphatic invasion (OR = 2.50; 95%CI: 1.46-4.28), and vascular invasion (OR = 1.80; 95%CI: 1.29-2.51), and higher TNM stage (III + IV) (OR = 0.31; 95%CI: 0.15-0.60). HIF-1α positive expression indicates a poor prognosis for patients with gastric cancer. Further studies are required to confirm these results.

Factors Associated With Oncologic Outcomes After Abdominoperineal Resection Compared With Restorative Resection for Low Rectal Cancer

Previous reports suggest that patients with rectal cancer undergoing abdominoperineal resection have worse oncologic outcomes in comparison with those undergoing restorative rectal resection. This study aimed to assess factors influencing oncologic outcomes for patients undergoing surgery for rectal cancer. This study is a retrospective review of prospectively gathered data. Data were gathered from a prospective cancer database. Patients were included who underwent radical resection for mid and lower third rectal cancer (1991-2006). The primary outcomes measured were the impact of various factors on perioperative outcomes, local recurrence, and disease-free survival for patients undergoing abdominoperineal resection. Four hundred thirteen (29%) patients underwent abdominoperineal resection and 993 (71%) underwent restorative resection for rectal cancer. Patients with abdominoperineal resection were older (p < 0.0001), had a higher mean ASA score (p < 0.001), worse tumor differentiation (p < 0.001), and higher tumor stage (p = 0.0001). Although overall morbidity was lower in the abdominoperineal resection group (p = 0.001), the length of stay was greater (p < 0.001). After a similar period of follow-up (5.2 ± 3.9 vs 5.3 ± 3.4 y, p = 0.58), local recurrence (7% vs 3%, p = 0.02) was higher after abdominoperineal resection, but overall survival (56% vs 71%, p < 0.001) and disease-free survival (54% vs 70%, p < 0.001) were lower. On multivariate analysis, higher stage, poor tumor differentiation, involved margins, and older age were associated with worse survival, whereas higher stage, poor tumor differentiation, and abdominoperineal resection were associated with greater recurrence. These worse oncologic outcomes persisted even when the groups were stratified based on the location of the cancer in mid or distal rectum and for patients with a clear circumferential margin. This study was limited by its retrospective nature. Technical factors alone are unlikely to be responsible for the worse outcomes after abdominoperineal resection in comparison with restorative resection. A combination of patient- and tumor-related factors that may have indicated the choice of the procedure also probably contribute to the worse outcomes. Because patients undergoing abdominoperineal resection represent a high risk for poor outcomes, management strategies need to consider all these factors during treatment.

Portal venous invasion: The single most independent risk factor for immediate postoperative recurrence of hepatocellular carcinoma

Despite improvements of treatment in hepatocellular carcinoma (HCC), the recurrence rate after curative hepatic resection still remains remarkably high. An immediate recurrence of HCC after surgery is frustrating. We tried to clarify risks of immediate postoperative recurrence of HCC; that is, within 4 months after curative hepatic resection. A total of 167 patients with HCC underwent hepatic resection; 60 had immediate postoperative recurrences (IPR group), and 107 had disease-free survival for more than 5 years (DFS group). Variables were compared between the two groups. Univariate analysis showed the following variables were significant risk factors for immediate postoperative recurrence of HCC: male sex, elevated serum aspartate aminotransferase level, greater amount of blood loss, longer operation time, worse tumor differentiation, higher tumor node metastasis stage, and presence of any of the following: intrahepatic metastasis, tumor-rupture, portal venous invasion, or microvascular invasion. In multivariate analysis, only portal venous invasion was a significant risk factor (odds ratio=3.2, P=0.03, standard error=0.5, Logistic regression analysis). Portal venous invasion may be the most significant risk factor for immediate postoperative recurrence of HCC. However, accurate assessment of this risk factor may require histological examination, limiting its utility as a preoperative predictor. Further research is necessary to definitively identify preoperative predictors.

Expression and mutation analysis of epidermal growth factor receptor in head and neck squamous cell carcinoma

The epidermal growth factor receptor (EGFR)-RAS-RAF-mitogen-activated protein kinase signaling cascade is an important pathway in cancer development and recent reports show that EGFR and its downstream signaling molecules are mutated in a number of cancers. We have analyzed 91 Japanese head and neck squamous cell carcinomas (HNSCC) and 12 HNSCC cell lines for mutations in EGFR, ErbB2, and K-ras. Exons encoding the hot-spot regions in the tyrosine kinase domain of both EGFR (exons 18, 19, and 21) and ErbB2 (exons 18-23), as well as exons 1 and 2 of K-ras were amplified by polymerase chain reaction and sequenced directly. EGFR expression was also analyzed in 65 HNSCC patients using immunohistochemistry. Only one silent mutation, C836T, was found in exon 21 of EGFR in the UT-SCC-16A cell line and its corresponding metastasic cell line UT-SCC-16B. No other mutation was found in EGFR, ErbB2, or K-ras. All tumors showed EGFR expression. In 21 (32%) tumors, EGFR was expressed weakly (+1). In 27 (42%) tumors it was expressed (+2) moderately, and in 17 (26%) tumors high expression (+3) was detected. Overexpression (+2, +3) was found in 44 tumors (68%). A worse tumor differentiation and a positive nodal stage were significantly associated with EGFR overexpression (P = 0.02, P = 0.032, respectively). Similar to patients from western ethnicity, mutations are absent or rare in Japanese HNSCC. Protein overexpression rather than mutation might be responsible for activation of the EGFR pathway in HNSCC.