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PURPOSE: To evaluate the predictive power of 2-[18F]FDG PET/CT-derived radiomic signature in human epidermal growth factor receptor 2 (HER2) status determination for primary breast cancer (BC) with equivocal immunohistochemistry (IHC) results for HER2. METHODS: A total of 154 primary BC with equivocal IHC results for HER2 were retrospectively enrolled in the study. First, the following five conventional PET parameters (SUVmax, SUVmean, SUVpeak, MTV, TLG) were measured and compared between HER2-positive and HER2-negative cohorts. After quantitative radiomic features extraction and reduction, the least absolute shrinkage and selection operator (LASSO) algorithm was used to establish a radiomic signature model. Then, the area under the curve (AUCs) after a receiver operator characteristic (ROC) analysis, accuracy, sensitivity and specificity were calculated and used as the main outcomes. Finally, a total of 37 BC patients from an external institution were included to perform an external validation. RESULTS: All the five conventional PET parameters were unable to discriminate between HER2-positive and HER2-negative cohorts for BC (P = 0.104-0.544). Whereas, the developed radiomic signature model was potentially predictive of HER2 status with an of AUC 0.887 (95% confidence interval [CI], 0.824-0.950) in the training cohort and 0.766 (95% CI, 0.616-0.916) in the validation cohort, respectively. For external validation, the AUC for the external test cohort was 0.788 (95% CI, 0.633-0.944). CONCLUSIONS: Radiomic signature based on 2-[18F]FDG PET/CT images was capable of non-invasively predicting the HER2 status with a comparable ability to FISH assay, especially for those with equivocal IHC results for HER2.

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One of the most prevalent forms of endocrine malignancies is thyroid cancer. Herein, we explored the mechanisms whereby miR-1246 is involved in thyroid cancer. Phosphoinositide 3-kinase adapter protein 1 (PIK3AP1) was identified as a potential miR-1246 target, with the online Gene Expression Omnibus (GEO) database. The binding between miR-1246 and PIK3AP1 and the dynamic role of these two molecules in downstream PI3K/AKT signaling were evaluated. Analysis of GEO data demonstrated significant miR-1246 downregulation in thyroid cancer, and we confirmed that overexpression of miR-1246 can inhibit migratory, invasive, and proliferative activity in vitro and tumor growth in vivo. Subsequent studies indicated that miR-1246 overexpression decreased the protein level of PIK3AP1 and the phosphorylation of PI3K and AKT, which were reversed by PIK3AP1 overexpression. At the same time, overexpression of PIK3AP1 also reversed the miR-1246 mimics-induced inhibition proliferative, migratory, and invasive activity, while promoting increases in apoptotic death, confirming that miR-1246 function was negatively correlated with that of PIK3AP1. Subsequently, we found that the miR-1246 mimics-induced inhibition of PI3K/AKT phosphorylation was reversed by the PI3K/AKT activator IGF-1. miR-1246 mimics inhibited proliferative, migratory, and invasive activity while promoting increases in apoptotic death, which were reversed by IGF-1. Furthermore, miR-1246 agomir can inhibit tumor growth in vivo. We confirmed that miR-1246 affects the signaling pathway of PI3K/AKT via targeting PIK3AP1 and inhibits the development of thyroid cancer. Thus, miR-1246 is a new therapeutic target for thyroid cancer.

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PURPOSE: 68 Ga-PSMA PET/CT has high specificity and sensitivity for the detection of both intraprostatic tumor focal lesions and metastasis. However, approximately 10% of primary prostate cancer are invisible on PSMA-PET (exhibit no or minimal uptake). In this work, we investigated whether machine learning-based radiomics models derived from PSMA-PET images could predict invisible intraprostatic lesions on 68 Ga-PSMA-11 PET in patients with primary prostate cancer. METHODS: In this retrospective study, patients with or without prostate cancer who underwent 68 Ga-PSMA PET/CT and presented negative on PSMA-PET image at either of two different institutions were included: institution 1 (between 2017 and 2020) for the training set and institution 2 (between 2019 and 2020) for the external test set. Three random forest (RF) models were built using selected features extracted from standard PET images, delayed PET images, and both standard and delayed PET images. Then, subsequent tenfold cross-validation was performed. In the test phase, the three RF models and PSA density (PSAD, cut-off value: 0.15 ng/ml/ml) were tested with the external test set. The area under the receiver operating characteristic curve (AUC) was calculated for the models and PSAD. The AUCs of the radiomics model and PSAD were compared. RESULTS: A total of 64 patients (39 with prostate cancer and 25 with benign prostate disease) were in the training set, and 36 (21 with prostate cancer and 15 with benign prostate disease) were in the test set. The average AUCs of the three RF models from tenfold cross-validation were 0.87 (95% CI: 0.72, 1.00), 0.86 (95% CI: 0.63, 1.00), and 0.91 (95% CI: 0.69, 1.00), respectively. In the test set, the AUCs of the three trained RF models and PSAD were 0.903 (95% CI: 0.830, 0.975), 0.856 (95% CI: 0.748, 0.964), 0.925 (95% CI:0.838, 1.00), and 0.662 (95% CI: 0.510, 0.813). The AUCs of the three radiomics models were higher than that of PSAD (0.903, 0.856, and 0.925 vs. 0.662, respectively; P = .007, P = .045, and P = .005, respectively). CONCLUSION: Random forest models developed by 68 Ga-PSMA-11 PET-based radiomics features were proven useful for accurate prediction of invisible intraprostatic lesion on 68 Ga-PSMA-11 PET in patients with primary prostate cancer and showed better diagnostic performance compared with PSAD.

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OBJECTIVE: It is unclear whether the receptor status of breast malignancy or the proportion of receptors expression is useful in the interpretation of 18F-FDG PET/CT. This study's purpose was to analyze whether 18F-FDG PET/CT was valuable for helping newly diagnosed breast cancer patients find suspected or unsuspected metastasis lesions based on the proportion of receptors expression. MATERIALS AND METHODS: Eighty newly diagnosed breast cancer patients were divided into six groups, containing N0 (no extraaxillary lymph node metastasis), N1 (extraaxillary lymph node metastasis), M0 (no distant metastasis), and M1 (distant metastasis) groups, C0 (no unsuspected metastasis), and C1 (unsuspected metastasis and treatment plan changed) detected by PET/CT. The main data, including the proportion of receptors ER (estrogen receptor), PR (progesterone receptor), and Her-2 (human epidermal growth factor receptor 2) status, were extracted. Simple correlation and logistic regression were preformed to analyze the association between them. RESULTS: Patients in N1 group had lower proportion of ER (%) and PR (%) than that in N0 group (ER: 2 [0-80] vs. 80 [15-95]; PR: 1 [0-10] vs. 20 [0-45], p<0.001). Moreover, the proportions of ER and PR were negatively correlated with N1 (ER: [r= -0.339, p= 0.002], PR: [r= -0.247, p= 0.011]) by simple correlation. Also, patients in C1 group had lower proportion of ER (%) and PR (%) than those in C0 group (ER: 10 [0-85] vs. 80 [15-90], p=0.026; PR: 1 [0-10] vs. 20 [0-70], p=0.041), while the distribution of ER and PR between M1 and M0 group had no significant difference. After the adjustment of traditional factors, the negative correlation between the proportion of ER (OR=0.986, 95% CI of OR [0.972-0.999], p=0.016) and C1 was found by logistic regression, cutoff value was 25% (ER) calculated by ROC (Receiver Operating Characteristic) curve (AUC [Area Under Curve]= 0.647, p=0.024). CONCLUSION: The proportion of ER in newly diagnosed breast cancer was negatively correlated with unsuspected metastasis detected by 18F-FDG PET/CT. 18F-FDG PET/CT might be recommended for newly diagnosed breast cancer patients with single lesions when the ER expression proportion is less than 25% to find unsuspected metastasis lesions and to modify treatment plan contrasted with conventional imaging and clinical examination.

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OBJECTIVE: Despite the effectiveness of radioiodine therapy (RIT), a few patients are refractory and show relapse, warranting repeated RIT (RRIT). The purpose of this study is to explore the risk factors for RRIT. SUBJECTS AND METHODS: We retrospectively analyzed 607 cases treated with iodine-131 (131I) between January 2013 and June 2016. Patients were categorized into two groups: RRIT (n=76) or non-RRIT (n=531). Univariate analysis and a final multivariate model were used to determine the risk factors for RRIT. P<0.05 indicated significance. After a mean 314.5MBq dose of 131I, 76 patients underwent secondary therapy. RESULTS: In the univariate analysis, the differences in terms of age, gender, family history of hyperthyroidism, course of disease, 24-hour 131I uptake, curve shape of 131I uptake, dose of 131I, thyroid peroxidase antibody, and thyrotrophin receptor antibody were not statistically significant (P>0.05). Anti-thyroid drug (ATD) treatment history, thyroid mass and dose of 131I were statistically significant (P values: 0.001, <0.001 and <0.001, respectively). Binary logistic analysis of factors that lead to repeated RIT showed a higher probability of ATD treatment history [OR=2.919, 95%CI (1.424, 5.982), P=0.003] and thyroid mass [OR=1.042, 95%CI(1.031, 1.052), P<0.001] associated with RRIT. CONCLUSION: Patients treated with ATD before radioiodine treatment and with larger thyroid mass are at a higher risk for repeated radioiodine treatment.

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Our study attempted to verify the effect of lncRNA BST2 interferon-stimulated positive regulator (BISPR) on cell viability, propagation and invasiveness of thyroid papillary carcinoma (TPC) and the interactive relationship between BISPR and miR-21-5p. Microarray analyzed the aberrant expression lncRNA BISPR in TPC. BISPR and miR-21-5p as well as B-cell lymphoma-2 (Bcl-2) expressions in TPC cells were determined by quantitative polymerase chain reaction (qRT-PCR) and Western blot. Cell counting kit-8 (CCK-8) assay, dual luciferase reporter assay, and transwell assay were conducted to manifest cell viability, propagation, and invasiveness of TPC cells. Flow cytometry was performed to determine the apoptosis and cell cycle of TPC cells. Mouse xenograft model was built to testify the effect of BISPR on tumor growth. BISPR in TPC tissues was over-expressed. BISPR knockdown restrained the propagation and invasiveness and enhanced the iodine uptake of TPC cells. The tumor-forming rate reduced after BISPR knockdown. In addition, miR-21-5p was lowly expressed in cancer tissues. BISPR promoted the development of TPC cells by inhibiting miR-21-5p expression. Bcl-2 was suppressed by miR-21-5p and sh-BISPR. BISPR, which was over-expressed in TPC, improved TPC cell viability, propagation, and invasiveness. MiR-21-5p was lowly expressed in TPC which inhibited Bcl-2 expression. BISPR stimulated propagation and invasiveness of TPC cells by depressing miR-21-5p.

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Considering the dilemma in papillary thyroid cancer treatment, this study intended to find solution in molecular respect. By probing into lncRNA-NEAT1/miR-129-5p/KLK7 interaction, this study would provide new targets for future treatment. Microarray analysis and R language package were applied to select possible lncRNA and miRNA. Luciferase reporter assay and RNA pull-down test were employed in the detection of target relationship between lncRNA and miRNA. Clone formation assay, flow cytometry analysis, wound healing assay, and transwell assay were, respectively, used to observe effects of lncRNA NEAT1/miR-129-5p/KLK7 to papillary thyroid cancer cells. Western blot and qRT-PCR were used to validate protein expressions and mRNA expressions in PTC tissues and cells. LncRNA NEAT1 was highly expressed in PTC tissues and cell lines and could deteriorate PTC by promoting proliferation, invasion, and migration accompanied by less apoptosis. Besides, miR-129-5p/lncRNA NEAT1 were found to negatively correlate with each other by direct target relationship and their combination suppressed the progression of PTC. KLK7, a highly expressed downstream protein in PTC tissues, could be directly regulated by miR-129-5p in a negative way. KLK7 accelerated the deterioration of PTC in vitro experiments which could be reversed by sh-lnc RNA NEAT1 and miR-129-5p mimics. In vivo experiments, silence of lncRNA NEAT1 restrain tumor growth in weight and volume. In conclusion, lncRNA NEAT1 suppression could inhibit PTC progression by upregulating miR-129-5p, which suppressed KLK7 expression either in vitro or vivo experiments.

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OBJECTIVE: To assess the effectiveness of radioactive iodine (RAI) ablation among patients with intermediate-risk differentiated thyroid cancer (DTC) following surgery. SUBJECTS AND METHODS: This population based study obtained information from the Surveillance, Epidemiology, and End Results (SEER) Program Research Data (1973-2013). National Cancer Institute, DCCPS, Surveillance Research Programme, Surveillance Systems Branch, released April 2016, based on the November 2015 submission. A total of 93,530 patients with primary thyroid cancer were identified in the SEER database during the period of 2004-2013 and focused on patients with DTC post-operatively treated or not treated with radioactive iodine (RAI). From these 9,127 patients were selected who had intermediate-risk DTC. A total of 8,601 patients were included in this study. For the overall population, the mean age of the population was 47.3 years and the majority were female (70.5%). RESULTS: Kaplan-Meier analysis found the mean overall survival time (os) for subjects with no radiation therapy which was 112.9 months and 114.9 months for those who received RAI ablation treatment (P<0.001). However, thyroid cancer-specific survival was not significantly different between treatment groups (117.7 vs. 118.0 months, log-rank test P=0.164). Overall survival and thyroid cancer-specific 1 year, 5 years, and 10-years survival rates were ≥89.8% and were similar between both treated groups. Multivariate analysis found age, gender, histologic type, and degree of lymph node metastases to be associated with OS, and age, gender, degree of lymph node metastasis and extra-thyroid tumor spread were independent factors for cancer-specific survival. In DTC patients with intermediate cancer risk multivariate analysis found that RAI was associated with a reduced risk of mortality compared with no radiation therapy (HR=0.710, 95% CI: 0.562-0.897, P=0.004) but no significant difference was seen in cancer-specific survival, either based on whole study population or on tumor size category. CONCLUSION: In DTC patients with intermediate cancer risk although postoperative RAI ablation following surgery showed a benefit in overall survival, no significant difference was seen in cancer-specific survival, either based on whole study population or on tumor size category.

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