LncRNA FAM83H-AS1 Contributes to the Radio-resistance and Proliferation in Liver Cancer through Stability FAM83H Protein.

BACKGROUND: Liver cancer (LC) is one of China's most common malignant tumors, with a high mortality rate, ranking third leading cause of death after gastric and esophageal cancer. Recent patents propose the LncRNA FAM83H-AS1 has been verified to perform a crucial role in the progression of LC. LncRNA FAM83H-AS1 has been verified to perform a crucial role in the progression of LC. However, the concrete mechanism remains to be pending further investigation. OBJECTIVE: This study aimed to explore the embedding mechanism of FAM83H-AS1 molecules in terms of radio sensitivity of LC and provide potentially effective therapeutic targets for LC therapy. METHODS: Quantitative real-time PCR (qRT-PCR) was conducted to measure the transcription levels of genes. Proliferation was determined via CCK8 and colony formation assays. Western blot was carried out to detect the relative protein expression. A xenograft mouse model was constructed to investigate the effect of LncRNA FAM83H-AS1 on tumor growth and radio-sensitivity in vivo. RESULTS: The levels of lncRNA FAM83H-AS1 were remarkably increased in LC. Knockdown of FAM83H-AS1 inhibited LC cell proliferation and colony survival fraction. Deletion of FAM83H-AS1 increased the sensitivity of LC cells to 4 Gy of X-ray radiation. In the xenograft model, radiotherapy combined with FAM83H-AS1 silencing significantly reduced tumor volume and weight. Overexpression of FAM83H reversed the effects of FAM83H-AS1 deletion on proliferation and colony survival fraction in LC cells. Moreover, the over-expressing of FAM83H also restored the tumor volume and weight reduction caused by the knockdown of FAM83H-AS1 or radiation in the xenograft model. CONCLUSION: Knockdown of lncRNA FAM83H-AS1 inhibited LC growth and enhanced radiosensitivity in LC. It has the potential to be a promising target for LC therapy.

Nomogram established using risk factors of early gastric cancer for predicting the lymph node metastasis.

BACKGROUND: For the prognosis of patients with early gastric cancer (EGC), lymph node metastasis (LNM) plays a crucial role. A thorough and precise evaluation of the patient for LNM is now required. AIM: To determine the factors influencing LNM and to construct a prediction model of LNM for EGC patients. METHODS: Clinical information and pathology data of 2217 EGC patients downloaded from the Surveillance, Epidemiology, and End Results database were collected and analyzed. Based on a 7:3 ratio, 1550 people were categorized into training sets and 667 people were assigned to testing sets, randomly. Based on the factors influencing LNM determined by the training sets, the nomogram was drawn and verified. RESULTS: Based on multivariate analysis, age at diagnosis, histology type, grade, T-stage, and size were risk factors of LNM for EGC. Besides, nomogram was drawn to predict the risk of LNM for EGC patients. Among the categorical variables, the effect of grade (well, moderate, and poor) was the most significant prognosis factor. For training sets and testing sets, respectively, area under the receiver-operating characteristic curve of nomograms were 0.751 [95% confidence interval (CI): 0.721-0.782] and 0.786 (95%CI: 0.742-0.830). In addition, the calibration curves showed that the prediction model of LNM had good consistency. CONCLUSION: Age at diagnosis, histology type, grade, T-stage, and tumor size were independent variables for LNM in EGC. Based on the above risk factors, prediction model may offer some guiding implications for the choice of subsequent therapeutic approaches for EGC.

The Failure Patterns of Nasopharygeal Carcinoma After Intensity-Modulated Radiotherapy and Implications for Surveillance.

Objective: To investigate the treatment outcomes, failure patterns and surveillance strategy in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT). Methods: A cohort of patients with NPC who had received the full course of IMRT between 2008 and 2012 were retrospectively analyzed. The failure patterns, time to recurrence, and detection methods were recorded. The survival was calculated using the Kaplan-Meier method. Multivariate proportional hazard regression models were used to test the prognostic factors. Results: In total, 2607 patients with NPC treated with IMRT were recruited. After the median follow-up of 112 months, 402 (15.4%) patients experienced distant metastasis, 225 (8.6%) patients had local recurrence, and 77 (3.0%) patients had regional recurrences. The 10-year overall survival (OS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were 74.5%, 90.1%, and 79.3%, respectively. The factors of male sex, age >50 years, lactate dehydrogenase >245 IU/L, advanced T classification, and advanced N classification were associated with poor OS. The N disease classification was the most important factor in predicting distant metastasis, and advanced T disease classification for high risk of local recurrence. For patients with T1 disease, the incidence of local recurrence was less than 2%, and the incidence of distant metastasis was less than 5% for patients with N0 disease. About 83% of the recurrence occurred in the first 5 years, and 20% of the recurrences showed no symptoms. Conclusion: High rate of local-regional control can be achieved for patients with NPC after IMRT, while distant metastasis remains as the major cause of failures. Patients with advanced N classification has high risk to develop distant metastasis, and most occurred within 5 years. Developing rational and individualized surveillance strategies based on the high risk factors of recurrence is helpful to balance the survival benefit and medical cost.

MicroRNA-195-3p inhibits cyclin dependent kinase 1 to induce radiosensitivity in nasopharyngeal carcinoma.

MicroRNAs (miRNAs) are revealed to participate in the progression of multiple malignancies, including nasopharyngeal carcinoma (NPC). This work is intended to decipher the function of microRNA-195-3p (miR-195-3p) in regulating the radiosensitivity of NPC cells and its mechanism. MiR-195-3p and cyclin-dependent kinase 1 (CDK1) expressions were detected in NPC tissues and cells using qRT-PCR and Western blot, respectively. Moreover, radiation-resistant cell lines were induced by continuous irradiation with different doses. Furthermore, the CCK-8 experiment, colony formation assay and flow cytometry were utilized to examine the growth, apoptosis and cell cycle of radioresistant cells. Bioinformatics prediction and dual-luciferase reporter gene assay were applied to prove the targeting relationship between miR-195-3p and CDK1 mRNA 3'UTR. The data showed that miR-195-3p was remarkably down-modulated in NPC tissues and was associated with increased tumor grade, lymph node metastasis and clinical stage of the patients. MiR-195-3p expression was significantly down-modulated in radiation-resistant NPC tissues and NPC cell lines relative to radiation-sensitive NPC tissues and human nasopharyngeal epithelial cells, while CDK1 expression was notably up-modulated. MiR-195-3p overexpression inhibited the growth of NPC cells, decreased radioresistance, promoted apoptosis, and impeded the cell cycle progression. CDK1 was a target gene of miR-195-3p, and CDK1 overexpression counteracted the effects of miR-195-3p on NPC cell growth, apoptosis, cell cycle progression and radiosensitivity. In summary, miR-195-3p improves the radiosensitivity of NPC cells by targeting and regulating CDK1.

PROZ May Serve as a Prognostic Biomarker for Early Hepatocellular Carcinoma.

OBJECTIVE: The occurrence and development of hepatocellular carcinoma (HCC) remain unclear. This study aimed to investigate potential diagnostic or prognostic markers for early HCC by applying bioinformatic analysis. METHODS: The gene expression profiles of early HCC and normal tissues from a TCGA dataset were used to identify differentially expressed genes (DEGs) and then analysed by weighted gene coexpression network analysis. The integrated genes were selected to construct the protein-protein interaction (PPI) network and determine the hub genes. The prognostic impact of the hub genes was then analysed. RESULTS: A total of 508 integrated genes were selected from the 615 DEGs and 8956 genes in the turquoise module. A PPI network was constructed, and the top 20 hub genes, including apolipoprotein A-IV (APOA4), fibrinogen gamma chain (FGG), vitamin K-dependent protein Z (PROZ), secreted phosphoprotein 24 (SPP2) and fetuin-B (FETUB), were identified. Only PROZ was significantly associated with the prognosis of early HCC. CONCLUSION: In this study, we demonstrated that the expression of PROZ was decreased in early HCC compared with normal liver controls, and low PROZ expression might result in poor overall survival of early HCC.

The Value of Cervical Node Features in Predicting Long-Term Survival of Nasopharyngeal Carcinoma in the Intensity-Modulated Radiotherapy Era.

OBJECTIVE: To investigate the prognostic value of cervical node features in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) and build a prognostic nomogram to predict the long-term survival. METHODS: In this study, 1752 patients after IMRT from 2008 to 2011 were recruited. The clinical and laboratory characteristics and the nodal features including the nodal number, maximum dimension diameter, extranodal extension (ENE), and cervical node necrosis (CNN) were retrospective analyzed. Univariate Cox and multivariate proportional hazard regression models were used to test the prognostic value of nodal features. Prognostic nomograms were established to predict survival. RESULTS: The 10-year distant metastases-free survival (DMFS) and disease-specific survival (DSS) rates were 86.5% and 80.8%, respectively. Multivariate analysis showed that age, sex, lactate dehydrogenase (LDH), CNN, ENE, T stage, and N stage were independent factors for DSS. Two nomograms-nomogram A (without nodal features) and nomogram B (with nodal features)-were built. The calibration curve for the probability of DSS showed good agreement between prediction by nomogram and the actual observation. The C-index of nomogram B was higher than that for nomogram A in predicting DSS (0.708 vs 0.676, P<0.01). CONCLUSION: The nodal features including ENE and CNN were negative prognostic factors for NPC, and the prognostic nomogram incorporating the nodal features was more accurate in predicting survival than the nomogram without nodal features.

Pattern classification for breast lesion on FFDM by integration of radiomics and deep features.

The radiomics model can be used in breast cancer detection via calculating quantitative image features. However, these features are explicitly designed, or handcrafted in advance, and this would limit their ability to characterize the lesion properly. This paper aims to build an integrated-features-based classification framework which cooperate the radiomics features and the deep features to classify benign and malignant breast lesions on full-filed digital mammography (FFDM). We propose a classification framework consists of three steps: (1) handcrafted features (HCFs) extraction and selection, (2) deep features (DFs) extraction and (3) the integrated features-based classification. Specifically, HCFs comprise the gray-level gap-length matrix (GLGLM) texture features and shape features, and DFs contain the pooled features and high-level fully-connected features. Then, a multi-classifier method is applied to construct our classification framework using integrated features for breast lesion classification. A total of 106 retrospective FFDM data (51 are malignant and 55 are benign) in both craniocaudal (CC) view and mediolateral oblique (MLO) view were included in this study. The areas under a receiver operating characteristic curve (AUC) value, accuracy, sensitivity, specificity and Youden's index, are used to examine the performance of our proposed method in differentiating benign and malignant breast lesion. Proposed framework trained on the concatenation of fully-connected features and HCFs can significantly improve classification performance (AUC of 94.6 %, accuracy of 96.4 %, sensitivity of 93.6 %, specificity of 98.9 % and Yonden's index of 92.5 %) compared with other features sets. Experimental results demonstrate that performance of proposed framework is improved, indicating the potential of concatenation of the fully-connected features and HCFs set in breast cancer patients.

Prognostic model and optimal treatment for patients with stage IVc nasopharyngeal carcinoma at diagnosis.

The treatment for patients with stage IVc nasopharyngeal carcinoma (NPC) at diagnosis was still controversial. In this study, we tried to build a prognostic score model and optimize the treatment for the patients. The prognostic model was based on the primary cohort involving 289 patients from 2002 to 2011 and the validation involving another 156 patients from 2012 to 2015.The prognostic model was built based on the hazard ratios of significant prognostic factors for overall survival (OS). By multivariate analysis, factors associated with poor OS were Karnofsky performance score ≤70, liver metastases, multiple-organ metastases, ≥2 metastatic lesions, lactate dehydrogenase >245 IU/I and poor response to chemotherapy (all P < 0.01). Based on these prognostic factors, patients were divided into the low-risk (0-2 points), intermediate-risk (3-6 points) and high-risk (≥7 points) groups. Five-year OS rates for the low-, intermediate- and high-risk groups were 49.3%, 9.7% and 0.0%, respectively (P < 0.01). Furthermore, loco-regional radiotherapy was associated with significantly better OS in low- and intermediate-risk patients, but not in high-risk patients. These results demonstrated that the prognostic score model based on six negative factors can effectively predict OS in patients with stage IVc NPC at diagnosis. Loco-regional radiotherapy may be beneficial for low- and intermediate-risk patients, but not for high-risk patients.

Palladin, an actin-associated protein, is required for adherens junction formation and intercellular adhesion in HCT116 colorectal cancer cells.

Palladin is a scaffold protein involved in the formation of actin-associated protein complexes. Gene expression array analysis on the poorly metastatic HCT116 colon cancer cell line and a metastatic derivative cell line (E1) with EMT (epithelial-mesenchymal transition) features showed a down-regulation of palladin gene expression in the latter. Knockdown of palladin expression in the HCT116 cells suppressed junctional localization of E-cadherin, reduced intercellular adhesion and collective cell migration, showing that palladin plays an important role in maintaining the integrity of adherens junctions. The acquisition of the EMT features by the E1 cell line was dependent on the Erk pathway. Inhibition of this pathway by U0126 treatment in E1 cells resulted in the re-expression of palladin, relocalization of E-cadherin to the adherens junctions and a reversal of EMT features. The re-establishment of intercellular adhesion was dependent on palladin expression. The down-regulation of palladin was also observed in poorly-differentiated tumor tubules and dissociated tumor cells that have undergone de-differentiation in human primary colon tumors. Our data show that palladin is an integral component of adherens junctions and plays a role in the localization of E-cadherin to the junctions. The loss of palladin may be an integral part of EMT, an early step in the metastatic spread of colon carcinoma.

[Combination of subradical external radiation and brachytherapy plus radical operation in the treatment of carcinoma of uterine cervix].

OBJECTIVE: To summarize retrospectively the 5-year survival rates and long-term complication of stage Ib-IIIa cervical carcinoma treated by combination of subradical external radiation and brachytherapy plus radical operation. METHODS: 106 patients with cervical carcinoma were all treated by radical hysterectomy and pelvic lymphadenectomy, of whom 78 had had preoperative radiotherapy (external radiation and brachytherapy), 16 combination of brachytherapy and radical operation, 12 adjuvant postoperative radiotherapy (external radiation and brachytherapy). (60)Co was used for external radiation, in which the point B dose was 25 - 30 Gy in preoperative radiation and 40 - 50 Gy in postoperative radiation. (192)Ir high-dose-rate afterloading unit was used in brachytherapy, with a dose of 6 - 18 Gy at point A. RESULTS: The follow up rate was 95.3%. The overall 5-year survival rates were 78.2% (61/78) in the preoperative radiotherapy group, 68.8% (11/16) in brachytherapy plus radical operation, 33.3% (4/12) in the postoperative radiotherapy group, showing a higher 5-year survival rate in the preoperative radiotherapy group than the postoperative radiotherapy group (P < 0.05). In stage II patients, the preoperative radiotherapy group -77.6% (45/58) also gave a higher survival than the postoperative radiotherapy group -25.0% (1/4) (P < 0.05). But all the other groups gave differences of insignificance. The chief long-term complications were radio-proctitis and cystitis, with incidences of 34.6% (27/78), 31.3% (5/16), 33.3% (4/12) in the preoperative radiotherapy group, brachytherapy plus radical operation group and the postoperative radiotherapy group (P > 0.05). CONCLUSION: The overall 5-year survival rate of combined subradical external radiation and brachytherapy plus radical operation was obviously higher than that of postoperative radiotherapy for stage Ib-IIIa and II patients, with statistically significant differences. However, the incidence of long-term complications give no statistical significance in the preoperative radiotherapy group or brachytherapy plus the operation group as compared with the postoperative radiotherapy group.