miR-3607, a biomarker of hepatocellular carcinoma invasion and aggressiveness: Its relationship with epithelial-mesenchymal transition process.

microRNA-3607 (miR-3607) has been identified as an important biomarker, and its aberrant expression exerts a significant role in tumorigenesis. However, the biological function of miR-3607 in hepatocellular carcinoma (HCC) needs to be deciphered comprehensively. Clinical samples of HCC patients, as well as normal cases, were derived from The Cancer Genome Atlas database. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting analyses were utilized to detect the expression levels of indicated genes. Cell counting kit-8 (CCK-8), colony formation, and transwell assays were performed to assess the effect of miR-3607 in HCC cell viability, migration, and invasion. Bioinformatics analysis and luciferase reporter gene assay was applied to screen the target genes of miR-3607 and verified the association between miR-3607 and its potential target gene. Our study showed that miR-3607 expression was decreased in HCC tissues and cell lines, and its downregulation was linked with poor outcomes of HCC patients. miR-3607 was noted to inhibit HCC cell growth, colony formation, migration, and invasion. Besides, minichromosome maintenance (MCM5) was a possible target gene of miR-3607 in HCC. Overexpression of MCM5 was observed in HCC and induced unfavorable prognosis. MCM5 expression had a negative correlation with miR-3607. MCM5 can abolish the suppressive impacts of miR-3607 on HCC cell malignant behaviors and the epithelial-mesenchymal transition (EMT) process. To sum up, our results unveiled that miR-3607 could inhibit HCC cell growth, migration, and invasion by regulating MCM5 and mediating EMT process, suggesting a new probable biomarker for further treatment of HCC.

LINC00511 as a ceRNA promotes cell malignant behaviors and correlates with prognosis of hepatocellular carcinoma patients by modulating miR-195/EYA1 axis.

BACKGROUND: Recently, a growing number of reports indicated that long non-coding RNAs (lncRNAs) were involved in the development of various cancers. However, the performance of LINC00511 is still limited in hepatocellular carcinoma (HCC). Thus, we attempted to assess the effect of LINC00511 and underlying mechanism in HCC progression. METHODS: TCGA and GEO database acted as supporters to provide us clinical samples data. Overall survival (OS) analyses were plotted using Kaplan-Meier method. Five cell lines were utilized to detect LINC00511 expression level and Cell Counting Kit-8 (CCK-8), colony formation and transwell assays were conducted to examine the effects on cell behaviors. The correlations between LINC00511 and miR-195 or eyes absent homolog 1 (EYA1) were confirmed by luciferase reporter assay. Quantitative real-time PCR and western blotting were fulfilled to ascertain the mRNA and protein expression levels. RESULTS: In this study, we found that LINC00511 was high-regulated in HCC tissue samples and cell lines, which might be linked with unfavorable prognosis of HCC patients and clinical parameters. Loss-of-function experiments determined that LINC00511 deficiency inhibited cell proliferation, colony formation and invasive activity in HepG2 cells, while gain-of-function experiments showed the counter impacts in Huh7 cells. Bioinformatics tools and luciferase reporter assays revealed that LINC00511 may act as a competing endogenous RNA (ceRNA) for miR-195 and positively correlate with EYA1, which was reinforced by rescue experiments. CONCLUSION: Taken together, these findings indicated that LINC00511 interacted with EYA1 promoted HCC development via mediating miR-195, proposing a promising therapeutic biomarker for HCC diagnosis and prognosis.

PDCD4 as a predictor of sensitivity to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients.

OBJECTIVE: The purpose of this study was to examine the role of programmed cell death 4 (PDCD4) expression in predicting tumor response to neoadjuvant chemoradiotherapy and outcomes for patients with locally advanced rectal cancer. METHODS: Clinicopathological factors and expression of PDCD4 were evaluated in 92 patients with LARC treated with nCRT. After the completion of therapy, 4 cases achieved clinical complete response (cCR), and thus the remaining 88 patients underwent a standardized total mesorectal excision procedure. There were 38 patients (41.3%) with a good response (TRG 3-4) and 54 (58.7%) with a poor one (TRG 0-2). RESULTS: Immunohistochemical staining analyses showed that patients with high expression of PDCD4 were more sensitive to nCRT than those with low PDCD4 expression (P=0.02). High PDCD4 expression before nCRT and good response (TRG3-4) were significantly associated with improved 5-year disease-free survival and 5-year overall survival (P<0.05). Multivariate analysis demonstrated that the pretreatment PDCD4 expression was an independent prognostic factor. CONCLUSION: Our study demonstrated that high expression of PDCD4 protein is a useful predictive factor for good tumor response to nCRT and good outcomes in patients with LARC.

Circulating lymphocytes as predictors of sensitivity to preoperative chemoradiotherapy in rectal cancer cases.

OBJECTIVE: The objective of this study was to identify clinical predictive factors for tumor response after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). METHODS: All factors were evaluated in 88 patients with LARC treated with nCRT. After a long period of 4-8 weeks of chemoradiotherapy, 3 patients achieved clinical complete response (cCR) and thus aggressive surgery was avoided, and the remaining 85 patients underwent a curative-intent operation. The response to nCRT was evaluated by tumor regression grade (TRG) system. RESULTS: There were 32 patients (36.4%) with good tumor regression (TRG 3-4) and 56 (63.6%) with poor tumor regression (TRG 0-2). Lymphocyte counts and ratios were higher in good response cases (P=0.01, 0.03, respectively) while neutrophil ratios and N/L ratios were higher in poor response cases (P=0.04, 0.02, respectively). High lymphocyte ratios before nCRT and good tumor regression (TRG3-4) were significantly associated with improved 5-year disease-free survival (P<0.05). Pretreatment nodal status was also significantly associated with 5-year disease-free survival and 5-year overall survival (P<0.05). Multivariate analysis confirmed that the pretreatment lymphocyte ratio and lymph nodal status were independent prognostic factors. CONCLUSION: Our study suggested that LARC patients with high lymphocyte ratios before nCRT would have good tumor response and high 5-year DFS and OS.

Cytokeratin 19 fragment antigen 21-1 as an independent predictor for definitive chemoradiotherapy sensitivity in esophageal squamous cell carcinoma.

BACKGROUND: Patients with esophageal squamous cell carcinoma (ESCC) undergoing definitive chemoradiotherapy (CRT) seem to have a disparity in therapeutic response. The identification of CRT sensitivity-related clinicopathological factors would be helpful for selecting patients most likely to benefit from CRT. Cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) and carcinoembryonic antigen (CEA) have been reported as useful tumor markers for esophageal cancer. The aim of this study was to examine the predictive value of CYFRA21-1 in comparison with CEA and other clinicopathological factors in patients with ESCC treated with definitive CRT. METHODS: Pretreatment serum CYFRA21-1 and CEA levels were measured by immunoradiometric assays. The relationships between pretreatment clinicopathological factors and the efficacy of CRT were analyzed. Overall survival (OS) was estimated by univariate and multivariate analysis. RESULTS: The results from a univariate analysis indicated that the efficacy of CRT was significantly associated with the serum levels of CYFRA21-1 and CEA before treatment (P = 0.001 and P = 0.023, respectively). It also indicated that the efficacy of CRT was significantly associated with the pretreatment tumor location (P = 0.041). By Logistic regression analysis, the independent predictive factor associated with efficacy of CRT was CYFRA21-1 (P = 0.002). The OS of the patients with high CYFRA 21-1 levels was worse than that of those with low CYFRA21-1 levels (P = 0.001). In multivariate analysis, a low level of CYFRA21-1 was the most significant independent predictor of good OS (P = 0.007). CONCLUSIONS: CEA and tumor location may be useful in predicting the sensitivity of ESCC to CRT. CYFRA21-1 may be an independent predictor for definitive CRT sensitivity in ESCC.

Prognostic significance of CYFRA21-1, CEA and hemoglobin in patients with esophageal squamous cancer undergoing concurrent chemoradiotherapy.

PURPOSE: To evaluate the prognostic value of serum CYFRA21-1, CEA and hemoglobin levels regarding long-term survival of patients with esophageal squamous cell carcinoma (ESCC) treated with concurrent chemoradiotherapy (CRT). METHODS: Age, gender, Karnofsky Performance Status (KPS), tumor location, tumor length, T stage, N stage and serum hemoglobin, and CYFRA21-1 and CEA levels before concurrent CRT were retrospectively investigated and related to outcome in 113 patients receiving 5-fluorouracil and cisplatin combined with radiotherapy for ESCC. The Kaplan-Meier method was used to analyze prognosis, the log-rank to compare groups, the Cox proportional hazards model for multivariate analysis, and ROC curve analysis for assessment of predictive performance of biologic markers. RESULTS: The median survival time was 20.1 months and the 1-, 2-, 3-, 5- year overall survival rates were 66.4%, 43.4%, 31.9% and 15.0%, respectively. Univariate analysis showed that factors associated with prognosis were KPS, tumor length, T-stage, N-stage, hemoglobin, CYFRA21-1 and CEA level. Multivariate analysis showed T-stage, N-stage, hemoglobin, CYFRA21-1 and CEA level were independent predictors of prognosis. By ROC curve, CYFRA21-1 and hemoglobin showed better predictive performance for OS than CEA (AUC= 0.791, 0.704, 0.545; P=0.000, 0.000, 0.409). CONCLUSIONS: Of all clinicopathological and molecular factors, T stage, N stage, hemoglobin, CYFRA21-1 and CEA level were independent predictors of prognosis for patients with ESCC treated with concurrent CRT. Among biomarkers, CYFRA21-1 and hemoglobin may have a better predictive potential than CEA for long-term outcomes.

[Correlation of VEGF and Ki67 expression with sensitivity to neoadjuvant chemoradiation in rectal adenocarcinoma].

OBJECTIVE: To investigate the correlation of expression of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (Ki67) with sensitivity to neoadjuvant chemoradiation in rectal adenocarcinoma. METHODS: Samples of pretreatment biopsies and the resected specimens after neoadjuvant therapy in 32 patients with rectal adenocarcinoma were collected, and the expression of Ki67 and VEGF were detected by immunohistochemistry using specific antibodies. The correlation of Ki67 and VEGF expression with clinicopathological factors were analyzed. RESULTS: The level of VEGF expression was significantly correlated with lymph node metastasis (P = 0.033), depth of tumor invasion (P = 0.007) and TNM stage (P = 0.016), but not with histological type, tumor size, age and gender of the patients (P > 0.05). However, VEGF expression was found to be negatively and significantly correlated with the sensitivity to neoadjuvant chemoradiation (P = 0.016), and a transient increase of VEGF expression was detected in the resected specimens after neoadjuvant therapy (P = 0.035). Ki67 labeling index (Ki67-LI) was found to be significantly correlated with lymph node metastasis (P = 0.028), but not with tumor size, age and gender of the patients (P > 0.05). It was also found that tumors with lower Ki67-LI expression were more sensitive to neoadjuvant therapy than that with higher expression of Ki67-LI (P = 0.032). In contrast with VEGF, the Ki67 expression level decreased after neoadjuvant therapy, but no statistical significance was found between pretreatment and posttreatment specimens (P > 0.05). CONCLUSION: The preliminary results of this study demonstrate that the expression of VEGF and Ki67 in pretreatment biopsy of rectal adenocarcinoma may be used as a biomarker to predict tumor response to neoadjuvant chemoradiation.

[Thermal dosimetric study on hyperthermia combined with radiotherapy for deep seated pelvic malignancies].

OBJECTIVE: To ascertain a clinically meaningful thermal dose unit-temperature equivalent minute (TEM) 42.5 degrees C and the relationship between TEM 42.5 degrees C and tumor response rate. METHODS: From August 1998 to December 2002, 49 patients with recurrent or metastatic malignancies in the pelvis were treated with hyperthermia combined with conventional radiotherapy. Direct thermometry with high resistance lead needle was used whenever possible to measure the temperature by inserting Teflon catheter into the tumor. TEM 42.5 degrees C was used as the thermal dose unit and the relationship between TEM 42.5 degrees C and tumor response rate was monitored. RESULTS: There was a positive correlation between response rate TEM 42.5 degrees C and the radiation dose. The tumor volume and number of heat treatment showed no influence on response. CONCLUSION: Both univariate analysis and multivariate logistic regression analysis indicate that there is a positive correlation between the response rate, TEM 42.5 degrees C and the radiation dose. TEM 42.5 degrees C may act as a useful thermal dose unit in the combination of hyperthermia and radiotherapy. To lower the incidence of complications in thermometry, direct thermometry with high resistance lead needle can be used to measure the temperature by inserting Teflon catheter into the deep-seated malignancies.