Risk Factors to Predict Ocular Metastasis in Older Adult Patients With Gastric Cancer:LDL, ApoA1, and CA724

Objective: The purpose of this study was to explore the risk factors for Ocular metastasis (OM) of Gastric cancer (GC). Methods: This is a retrospective cohort study. A total of 1165 patients with GC were enrolled in this study and divided into OM and non-ocular metastasis (NOM) groups. Chi-square and independent samples t tests were used to determine whether differences in demographic characteristics and serological indicators (SI) between the two groups were significant. In addition, binary logistic regression was used to analyze the value of various SI as risk factors for OM in patients with GC. The statistical threshold was set as P < .05. Finally, receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value of various SI in differentiating the occurrence of OM in patients with GC. Results: The incidence of OM in older adults with GC was 1.1%. Adenocarcinoma was the most common type of GC in both groups, and there was no significant difference in demographic characteristics between the groups. Low-density lipoprotein (LDL), carbohydrate antigen-724 (CA724), and carcinoembryonic antigen levels were significantly higher in the OM group than the NOM group, while those of apolipoprotein A1 (ApoA1) were significantly lower in the OM than the NOM group. Binary logistic analysis showed that LDL, ApoA1, and CA724 were independent risk factors for OM in patients with GC ( P < .001, P = .033, and P = .008, respectively). ROC curve analysis generated area under the curve (AUC) values of 0.881, 0.576, and 0.906 for LDL, ApoA1, and CA724, respectively. In addition, combined analysis of LDL, ApoA1, and CA724 generated the highest AUC value of 0.924 ( P < .001). Conclusion: Among SI, LDL, ApoA1, and CA724 have predictive value for the occurrence of OM in GC, with the three factors combined having the highest value.

Transcriptomic Analysis of Breast Cancer Patients Sensitive and Resistant to Chemotherapy: Looking for Overall Survival and Drug Resistance Biomarkers

Worldwide breast cancer ranks first in mortality and incidence rates in women over 20 years old. Rather than one disease, breast cancer is a heterogeneous group of diseases that express distinct molecular profiles. Neoadjuvant chemotherapy is an important therapeutic strategy for breast cancer patients independently of their molecular subtype, with the drawback of resistance development. In addition, chemotherapy has adverse effects that combined with resistance could contribute to lower overall survival. Although great efforts have been made to find diagnostic and prognostic biomarkers for breast cancer and for response to targeted and immune therapy for this pathology, little has been explored regarding biomarkers of response to anthracyclines and taxanes based neoadjuvant chemotherapy. This work aimed to evaluate the molecular profile of patients who received neoadjuvant chemotherapy to identify differentially expressed genes (DEGs) that could be used as biomarkers of chemotherapy response and overall survival. Breast cancer patients who were candidates for neoadjuvant chemotherapy were enrolled in this study. After treatment and according to their pathological response, they were assigned as sensitive or resistant. To evaluate DEGs, Gene Ontology, Kyoto Encyclopedia Gene and Genome (KEGG), and protein–protein interactions, RNA-seq information from all patients was obtained by next-generation sequencing. A total of 1985 DEGs were found, and KEGG analysis indicated a great number of DEGs in metabolic pathways, pathways in cancer, cytokine–cytokine receptor interactions, and neuroactive ligand-receptor interactions. A selection of 73 DEGs was used further for an analysis of overall survival using the METABRIC study and the ductal carcinoma dataset of The Cancer Genome Atlas (TCGA) database. Nine DEGs correlated with overall survival, of which the subexpression of C1QTNF3, CTF1, OLFML3, PLA2R1, PODN, KRT15, HLA-A, and the overexpression of TUBB and TCP1 were found in resistant patients and related to patients with lower overall survival.

Comparison of Absolute Dose Achievable Between Helical Tomotherapy and RapidArc in Total Dura Mater Irradiation for Child Cancer

Background and Purpose: In this study, the absolute dose achievable between helical tomotherapy (HT) plans and RapidArc (RA) plans for total dura mater irradiation (TDMI) was compared. Materials and methods: A planning study was conducted on nine children's case datasets with dura mater metastasis of neuroblastoma. The target included the entire calvarium and skull base and formed a closed volume with a certain thickness around the brain. HT and RA plans with four coplanar full arcs (RA4) with half-field technique were generated for the comparison of absolute dose achievable. In total, 30.6 Gy was prescribed as D95% (ie, dose to 95% of PTV volume). Results: In the dosimetric comparison between the two modalities, HT provided more homogenous dose distribution than RA4 (mean HI5−95%: 1.046 vs 1.088, P < .001). The V107% and D2Gy of PTV in HT versus RA4 were 3.06% versus 30.47% and 32.59 Gy versus 33.45 Gy, respectively. HT reduced the Dmean and V5Gy of the brain, brainstem, and hippocampus by 25%–48% and 27%–56% compared with RA4, respectively. Conclusion: Both techniques could provide sufficient coverage for targets, but HT offered more homogenous dose to PTV and lower dose to the central region of the brain involving the brainstem and hippocampus. RA4 could be completed in a shorter time with lower MUs, but with relatively higher dose to the brain or hippocampus. In terms of dosimetry, HT may improve long-term cognitive decline in these young pediatric patients with TDMI.

PHLPP1 Overexpression was Associated With a Good Prognosis With Decreased AKT Activity in Gastric Cancer

Introduction: The aim of this study was to perform a clinicopathologic analysis of PHLPP1 expression in gastric cancer patients and analyze AKT activity with chemotherapy drug treatment in cancer subtypes. Materials and Methods: Surgically resected gastric cancer tissue specimens were obtained from 309 patients who underwent gastrectomy, and PHLPP1 expression was validated by tissue microarray analysis with immunohistochemistry. We assessed whether PHLPP1 selectively dephosphorylates Ser473 of AKT in an in-vitro study. Results: We found that the PHLPP1 overexpression (OE) group showed significantly greater proportions of differentiated subtype samples and early T stage samples, lower lymph node metastasis, and lower TNM stage than the PHLPP1 underexpression (UE) group. The overall survival of the PHLPP1-OE group was significantly higher (53.39 ± 0.96 months) than that of the PHLPP1-UE group (47.82 ± 2.57 months) ( P = .01). In vitro analysis, we found that the PHLPP1-OE group showed a significant decrease in relative AKT S-473 levels in both cell lines (MKN-74 and KATO-III). We found that treatment with chemotherapy drugs decreased the activity of Ser473 in the MKN-74 cell line with PHLPP1 OE, but it did not affect the activity of Ser473 in KATO-III cells. Conclusion: We found that patients who overexpressed PHLPP1 showed low recurrence and good prognosis. PHLPP1 was found to work by lowering the activity of AKT Ser473 in gastric cancer. Additionally, we found a clue regarding the mechanism of chemotherapeutic drug resistance in a cell line of signet ring cell origin and will uncover this mechanism in the future.

Score for the Risk and Overall Survival of Lung Metastasis in Patients First Diagnosed With Soft Tissue Sarcoma: A Novel Nomogram-Based Risk Assessment System

Background: Metastatic soft tissue sarcoma (STS) patients have a poor prognosis with a 3-year survival rate of 25%. About 30% of them present lung metastases (LM). This study aimed to construct 2 nomograms to predict the risk of LM and overall survival of STS patients with LM. Materials and Methods: The data of patients were derived from the Surveillance, Epidemiology, and End Results database during the period of 2010 to 2015. Logistic and Cox analysis was performed to determine the independent risk factors and prognostic factors of STS patients with LM, respectively. Afterward, 2 nomograms were, respectively, established based on these factors. The performance of the developed nomogram was evaluated with receiver operating characteristic curves, area under the curve (AUC) calibration curves, and decision curve analysis (DCA). Results: A total of 7643 patients with STS were included in this study. The independent predictors of LM in first-diagnosed STS patients were N stage, grade, histologic type, and tumor size. The independent prognostic factors for STS patients with LM were age, N stage, surgery, and chemotherapy. The AUCs of the diagnostic nomogram were 0.806 in the training set and 0.799 in the testing set. For the prognostic nomogram, the time-dependent AUC values of the training and testing set suggested a favorable performance and discrimination of the nomogram. The 1-, 2-, and 3-year AUC values were 0.698, 0.718, and 0.715 in the training set, and 0.669, 0.612, and 0717 in the testing set, respectively. Furthermore, for the 2 nomograms, calibration curves indicated satisfactory agreement between prediction and actual survival, and DCA indicated its clinical usefulness. Conclusion: In this study, grade, histology, N stage, and tumor size were identified as independent risk factors of LM in STS patients, age, chemotherapy surgery, and N stage were identified as independent prognostic factors of STS patients with LM, these developed nomograms may be an effective tool for accurately predicting the risk and prognosis of newly diagnosed patients with LM.

MicroRNA Expression Profiling in Hydatidiform Mole for the Prediction of Postmolar GTN

Objectives: The primary aim of the study was to identify miRNAs that were differentially expressed between complete hydatidiform moles (CHMs) that turned out to be gestational trophoblastic neoplasia (GTN) [GTN moles] and CHMs that regressed spontaneously after evacuation [remission moles]. The secondary aim was to study the profiles of miRNA expressions in CHMs. Methods: A case-control study was conducted on GTN moles and remission moles. We quantitatively assessed the expression of 800 human miRNAs from molar tissues using Nanostring nCounter. Results: From a pilot study, 21 miRNAs were significantly downregulated in GTN moles compared to the remission moles. Five of them (miR-566, miR-608, miR-1226-3p, miR-548ar-3p and miR-514a-3p) were downregulated for >4 folds. MiR-608 was selected as a candidate for further analysis on 18 CHMs (9 remission moles and 9 GTN moles) due to its striking association with malignant formation. MiR-608 expression was slightly lower in GTN moles compared to the remission moles, that is, 2.22 folds change [p = 0.063]. Conclusion: We identified 21 miRNAs that were differentially expressed between GTN moles and remission moles suggesting that miRNA profiles can distinguish between the two groups. Although not reaching statistically significant, miR-608 expression was slightly lower in GTN moles compared to remission moles.

Dose Reduction and Low-Contrast Detectability Using Iterative CBCT Reconstruction Algorithm for Radiotherapy

Introduction: Several studies have reported the relation between the imaging dose and secondary cancer risk and have emphasized the need to minimize the additional imaging dose as low as reasonably achievable. The iterative cone-beam computed tomography (iCBCT) algorithm can improve the image quality by utilizing scatter correction and statistical reconstruction. We investigate the use of a novel iCBCT reconstruction algorithm to reduce the patient dose while maintaining low-contrast detectability and registration accuracy. Methods: Catphan and anthropomorphic phantoms were analyzed. All CBCT images were acquired with varying dose levels and reconstructed with a Feldkamp–Davis–Kress algorithm-based CBCT (FDK-CBCT) and iCBCT. The low-contrast detectability was subjectively assessed using a 9-point scale by 4 reviewers and objectively assessed using structure similarity index (SSIM). The soft tissue-based registration error was analyzed for each dose level and reconstruction technique. Results: The results of subjective low-contrast detectability found that the iCBCT acquired at two-thirds of a dose was superior to the FDK-CBCT acquired at a full dose (6.4 vs 5.4). Relative to FDK-CBCT acquired at full dose, SSIM was higher for iCBCT acquired at one-sixth dose in head and head and neck region while equivalent with iCBCT acquired at two-thirds dose in pelvis region. The soft tissue-based registration was 2.2 and 0.6 mm for FDK-CBCT and iCBCT, respectively. Conclusion: Use of iCBCT reconstruction algorithm can generally reduce the patient dose by approximately two-thirds compared to conventional reconstruction methods while maintaining low-contrast detectability and accuracy of registration.

Prognostic and Clinicopathologic Significance of Neutrophil-to-Lymphocyte Ratio in Esophageal Cancer: An Update Meta-Analysis

Background: Esophageal cancer is one of the most common cancers with significant morbidity and mortality. It is important to predict the prognosis of patients. The purpose of this study was to comprehensively assess the prognostic and clinicopathologic significance of NLR in patients with esophageal cancer. Methods: A systematic literature search was performed using PubMed, Cochrane Library, Embase, Web of Science, MEDLINE, and CNKI. This meta-analysis was conducted in accordance with PRISMA guidelines. Hazard ratio (HR) with 95% confidence interval (CI) was used as the effect estimation to evaluate the prognostic role of NLR. Odds ratio (OR) was used to evaluate the relation between NLR and clinicopathologic characteristics. Results: A total of 8431 patients from 32 studies were included in this meta-analysis. The pooled results showed that elevated NLR might predict poor prognosis: The factors considered included overall survival (OS) (HR, 1.57; 95% CI, 1.40-1.75; P < .001), cancer-specific survival (CSS) (HR, 1.28; 95% CI, 1.09-1.49; P < .001), progression-free survival (PFS) (HR, 1.45; 95% CI, 1.29-1.72; P < .001), and disease-free survival (DFS) (HR,1.58; 95% CI, 1.27-1.97; P < .001). High NLR was also associated with tumor differentiation, tumor length, tumor invasion depth, lymph node metastasis, and clinical stage. No significant association was observed between NLR and metastasis stage (OR, 1.69; 95% CI, 0.98-2.98; P = .058). Conclusions: The results of this meta-analysis suggest that elevated NLR value might predict poor prognosis (OS, CSS, PFS, and DFS), according to abnormal clinicopathologic parameters.

The Potential Diagnostic Accuracy of Circulating MicroRNAs for Leukemia: A Meta-Analysis

Background: Leukemia is a common malignant disease in the human blood system. Many researchers have proposed circulating microRNAs as biomarkers for the diagnosis of leukemia. We conducted a meta-analysis to evaluate the diagnostic accuracy of circulating miRNAs in the diagnosis of leukemia. Methods: A comprehensive literature search (updated to October 13, 2020) in PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang database and China National Knowledge Infrastructure (CNKI) was performed to identify eligible studies. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) for diagnosing leukemia were pooled for both overall and subgroup analysis. The meta-regression and subgroup analysis were performed to explore heterogeneity and Deeks’ funnel plot was used to assess publication bias. Results: 49 studies from 22 publications with a total of 3,489 leukemia patients and 2,756 healthy controls were included in this meta-analysis. The overall sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under the curve were 0.83, 0.92, 10.8, 0.18, 59 and 0.94, respectively. Subgroup analysis shows that the microRNA clusters of plasma type could carry out a better diagnostic accuracy of leukemia patients. In addition, publication bias was not found. Conclusions: Circulating microRNAs can be used as a promising noninvasive biomarker in the early diagnosis of leukemia.

The Effect of Heterogenous Subregions in Glioblastomas on Survival Stratification: A Radiomics Analysis Using the Multimodality MRI

Intratumor heterogeneity is partly responsible for the poor prognosis of glioblastoma (GBM) patients. In this study, we aimed to assess the effect of different heterogeneous subregions of GBM on overall survival (OS) stratification. A total of 105 GBM patients were retrospectively enrolled and divided into long-term and short-term OS groups. Four MRI sequences, including contrast-enhanced T1-weighted imaging (T1C), T1, T2, and FLAIR, were collected for each patient. Then, 4 heterogeneous subregions, i.e. the region of entire abnormality (rEA), the regions of contrast-enhanced tumor (rCET), necrosis (rNec) and edema/non-contrast-enhanced tumor (rE/nCET), were manually drawn from the 4 MRI sequences. For each subregion, 50 radiomics features were extracted. The stratification performance of 4 heterogeneous subregions, as well as the performances of 4 MRI sequences, was evaluated both alone and in combination. Our results showed that rEA was superior in stratifying long-and short-term OS. For the 4 MRI sequences used in this study, the FLAIR sequence demonstrated the best performance of survival stratification based on the manual delineation of heterogeneous subregions. Our results suggest that heterogeneous subregions of GBMs contain different prognostic information, which should be considered when investigating survival stratification in patients with GBM.