Prognostic value of pretreatment FDG PET-CT for short-term efficacy of radioactive iodine-125 seed implantation in patients with NSCLC.

PURPOSE: To analyze the short-term clinical response of radioactive iodine-125 seed implantation (I125-SI) in patients of non-small-cell lung cancer (NSCLC) and explore possible correlations of various metabolic parameters of pretreatment FDG PET-CT with the short-term efficacy of this treatment modality. METHODS AND MATERIALS: The present study is a retrospective analysis of treatment records of 46 NSCLC patients who were treated with I125-SI for lung tumors in Tianjin First Central Hospital from January 2016 to December 2018. The correlation among parameters D90, gender, pathological pattern, age, maximum tumor diameter, Metabolic Tumor Volume (MTV), SUVmax, SUVpeak, SUVmean, Total Lesion Glycolysis (TLG), High metabolic tumor cell ratio (HMR) and Carcinoembryonic antigen(CEA)with short-term efficacy of I125-SI was analyzed by two independent-sample t-test, Mann-Whitney U test or Chi-squared test and binary logistic regression. RESULTS: After uneventful completion of treatment, patients were followed up at regular intervals. At the first month followup, none of cases showed complete response (CR), while 4 cases showed partial response (PR). After 3 months, there were 2 cases of CR, and 25 cases of PR; after 6 months, there were 5 cases of CR, and 27 cases of PR. D90 (p= 0.028, OR:1.075, 95% CI:1.008-1.147), MTV (p= 0.026, OR: 0.918, 95% CI: 0.851-0.990), HMR (p= 0.020, OR: 0.003, 95% CI: 0-0.407) were independent predictors for the short-term efficacy. The predictive accuracy of MTV was medium (AUC = 0.781; cutoff value = 44.58). However, the predictive accuracies of D90 and HMR were low, with the values of AUC being 0.650 for both the parameters, and their cutoff values being 127.8 Gy and 0.27 respectively. CONCLUSIONS: I125-SI is an effective therapy with few complications in NSCLC patients. Small MTV, high D90 and low HRM were found to be linked with better local control at 6 months postimplantation.

DNA methylation loci identification for pan-cancer early-stage diagnosis and prognosis using a new distributed parallel partial least squares method.

Aberrant methylation is one of the early detectable events in many tumors, which is very promising for pan-cancer early-stage diagnosis and prognosis. To efficiently analyze the big pan-cancer methylation data and to overcome the co-methylation phenomenon, a MapReduce-based distributed and parallel-designed partial least squares approach was proposed. The large-scale high-dimensional methylation data were first decomposed into distributed blocks according to their genome locations. A distributed and parallel data processing strategy was proposed based on the framework of MapReduce, and then latent variables were further extracted for each distributed block. A set of pan-cancer signatures through a differential co-expression network followed by statistical tests was further identified based on their gene expression profiles. In total, 15 TCGA and 3 GEO datasets were used as the training and testing data, respectively, to verify our method. As a result, 22,000 potential methylation loci were selected as highly related loci with early-stage pan-cancer diagnosis. Of these, 67 methylation loci were further identified as pan-cancer signatures considering their gene expression as well. The survival analysis as well as pathway enrichment analysis on them shows that not only these loci may serve as potential drug targets, but also the proposed method may serve as a uniform framework for signature identification with big data.

LBX2-AS1 Activates FSTL3 by Binding to Transcription Factor RARα to Foster Proliferation, Migration, and Invasion of Thyroid Cancer.

Background: Thyroid cancer is a frequent endocrine tumor in women. It is of great significance to investigate the molecular mechanism of progression of thyroid cancer. Methods: Gene expression data set and clinical data were downloaded from The Cancer Genome Atlas database for differential expression analysis. The triplet of downstream transcription factors (TFs) and modulatory genes of target lncRNA in thyroid cancer was predicted by the lncMAP database. mRNA and protein expression of lncRNA LBX2-AS1, RARα, and FSTL3 were detected by qRT-PCR and western blot. The localization of lncRNA LBX2-AS1 in cells was tested by Fluorescence in situ hybridization assay. The RNA immunoprecipitation assay was applied to verify the binding relationship between lncRNA LBX2-AS1 and FSTL3. ChIP and dual-luciferase assays were used to prove the binding relationship between RARα and FSTL3. Cell function experiments were used to test cell proliferation, migration and invasion in each treatment group. The role of lncRNA LBX2-AS1 in thyroid cancer progression was also confirmed in nude mice. Results: Bioinformatics analysis indicated that lncRNA LBX2-AS1, RARα, FSTL3 were remarkably fostered in thyroid cancer tissue, and LBX2-AS1 was evidently correlated with clinical features. The LncMAP triplet prediction showed that LBX2-AS1 recruited TF RARα to modulate FSTL3. RIP assay confirmed that LBX2-AS1 was prominently enriched on RARα. ChIP and dual-luciferase report assays unveiled that RARα bound to the promoter region of FSTL3 and functioned as a TF. Cell function experiments uncovered that LBX2-AS1 boosted the progression of thyroid cancer. The rescue experiments showed that LBX2-AS1 recruited the TF RARα to hasten the transcription activity of FSTL3 and thus promoted the development of thyroid cancer. Conclusion: The integrative results demonstrated that LBX2-AS1 activated FSTL3 by binding to TF RARα to hasten proliferation, migration and invasion of thyroid cancer.

Predicting tumor recurrence using metabolic indices of 18F-FDG PET/CT prior to orthotopic liver transplantationfor hepatocellular carcinoma.

The present study analyzed the ability of metabolic burden indices from 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) to predict tumor recurrence following orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC). Seven major metabolic indices were measured by 18F-FDG PET/CT in 93 patients with HCC, prior to OLT. The Mann-Whitney U test was then used to predict the association of metabolic indices, including the maximum standardized uptake value (SUVmax), tumor-to-mediastinum SUV ratio, tumor-to-normal-liver SUV ratio, SUV normalized to lean body mass metabolic tumor volume (MTV), total lesion glycolysis (TLG) and uptake-volume product (UVP), with the recurrence risk. The Deauville-like scoring system was used to quantify the recurrence risk. Univariate and multivariable Cox regression models were performed to determine survival rate. The results showed that Deauville-like score (PET-negative vs. -positive), MTV (cutoff value, 13.36), TLG (cutoff value, 62.21) and UVP (cutoff value, 66.60) had high prediction performance for tumor recurrence (P<0.05). TLG had the highest receiver operating characteristics area under the curve of 0.725. Among the clinical factors, high level of α-fetoprotein (AFP, ≥144 ng/ml), Milan criteria, tumor number (>3), involvement of both right and left lobes, and tumor size (>5 cm) were found to be significant predictors of tumor recurrence. Patients in the low metabolic group had longer recurrence-free survival (RFS) times compared with those in the high metabolic group, regardless of whether they met the Milan criteria or not. AFP, uptake-volume product according the SUV mean of mediastinum (UVP-M), Milan criteria, lymph node metastasis, and the number of tumors were significant prognostic factors for RFS (P<0.05) in both univariate and multivariate survival analyses. Additionally, the MVI was a significant prognostic factor based on univariate survival analyses. Overall, the present study demonstrated the metabolic burden indices measured by PET/CT, Deauville-like score, MTV, TLG and UVP as significant prognostic factors in patients with HCC following OLT. The combination of metabolic indices measured by PET/CT and the existing criteria, such as the Milan criteria, may play an important role in evaluating the suitability of OLT in specific patients.