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For the purpose of obtaining the smaller uncertainties for Hp(3) and Dp lens in 90Sr/90Y beta reference fields, a new dose determination method based on the Monte-Carlo simulation was proposed. The conversion coefficients from the absorbed dose in air, at the reference point of the extrapolation ionisation chamber, Dair, det to Hp(3; α) and the conversion factors from Dair, det to Dp lens(α) were calculated with EGSnrc, respectively, for the irradiation angles from 0° to 60°. Compared with the dose determination method in International Organization for Standardization (ISO) 6980 standard, the uncertainty reductions of 7.7–52.8% for Hp(3; α) and 7.9–55.0% for Dp lens(α) were achieved, respectively. In addition, for the conversion coefficients from the reference absorbed dose DR to Hp(3; α), the calculations were performed for more irradiation conditions, which are not included in the current ISO 6980 standard. For the calculations of the conversion factors from DR to Dp lens(α), the eye and head phantoms with Chinese characteristics were utilised, which makes the conversion factors more suitable for use in China.

Background: Germline DNA damage repair (DDR) mutations has been associated with increased cancer risk, PARP inhibitor therapeutic opportunity for breast cancer (BC) patients. However, the profile of germline mutations in BC covering comprehensive DDR genes remains unclear. Methods: A total of 341 women with breast cancer who tested 102 germline related genes (including 50 DDR genes) between April 2021 to May 2022 in Guangdong Provincial People’s Hospital were identified. Variants were classified into pathogenic, likely pathogenic, variant of uncertain significance (VUS), likely benign and benign groups according to the ACMG/AMP Standards and Guidelines. We defined pathogenic and likely pathogenic variants as deleterious mutations. Results: The median age of 341 breast cancer patients was 48 (range, 20-89) at the first diagnosis of BC. A total of 47 patients (13.78%) carried 53 deleterious germline variants in 21 cancer predisposition genes, 16 of which were DDR genes. DDR deleterious mutations were detected in genes including BRCA2 (n=18), BRCA1(n=7), FANCA (n=4), PMS2 (n=4), PALB2(n=2), RECQL4(n=2), PALB2 (n=2), etc. The younger age at diagnosis (less than 40-year-old) were significantly associated with deleterious mutations in DDR pathway(P=0.02). At least one VUS was identified in 238 (69.79%) patients. The top 5 DDR VUS genes were FANCM (n=21), ATM (n=20), RAD54L (n=17), FANCD2 (n=15) and ATR (n=14). Breast or ovarian cancer family history were significantly correlated with VUS germline mutations in DDR pathway(P=0.039). Interesting, we found that patients with pCR efficacy of neoadjuvant therapy were more likely to have VUS mutations in DDR pathway (table 1). Conclusion: We provided a comprehensive view of germline DDR gene mutations in BC patients and also analyzed the association between clinical characteristics and germline DDR mutation status. DDR mutations are prevalent in Chinese BC patients. Patients with younger and breast or ovarian cancer family history were more likely to carry DDR alterations. Moreover, patients with higher frequency of DDR VUS mutations may benefit from neoadjuvant therapy. Table 1. Clinicopathological characteristics between germline mutation carriers and non-carriers Citation Format: Ning Liao, Li Cao, Guochun Zhang, Junyun Wang, Airong Yang, Yulei Wang, Kai Li, Lingzhu Wen, Chongyang Ren, Minghan Jia, Cheukfai Li, Hsiaopei Mok, Bo Chen, Jianguo Lai, Weikai Xiao. Comprehensive analysis of DNA damage repair gene germline mutations in Chinese breast cancer patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-12-06.

There were limitations existing in programmed cell-death ligand 1 (PD-L1) as predictive biomarkers for breast cancer (BC), hence exploring the correlation between PD-L1 levels and other biomarkers in BC may become a very useful therapeutic clinical tool.A total of 301 Chinese patients with different BC subtypes including 47 HR+/HER2+, 185 HR+/HER2-, 38 HR-/HER2+, and 31 triple-negative breast cancer (TNBC) were enrolled in our study. Next-generation sequencing based Yuansu450 gene panel was used for genomic alteration identification and PD-L1 expression was tested using immunohistochemistry.The most prevalent BC-related mutations were TP53 mutations, followed by mutations in PIK3CA, ERBB2, CDK12, and GATA3 in our Chinese cohort. We found that mutations DDR2 and MYCL were only mutated in HR-/HER2+ subtype, whereas H3-3A and NRAS mutations were only occurred in HR-/HER2- subtype. The percentage of patients with PD-L1-positive expression was higher in patients with HR-/HER2- mainly due to the percentage of PD-L1-high level. Mutational frequencies of TP53, MYC, FAT4, PBRM1, PREX2 were observed to have significant differences among patients with different BC subtypes based on PD-L1 levels. Moreover, a positive correlation was observed between TMB and PD-L1 level in HR+/HER2- subtype, and showed that the proportion of patients with high PD-L1 expression was higher than that of patients with low PD-L1 expression in the HR+/HER2- and HR+/HER2+ cohorts with high Ki67 expression.The genomic alterations based on PD-L1 and other biomarkers of different cohorts may provide more possibilities for the treatment of BC with different subtypes.

Reviews and experimental verification have found that existing solution methods can be used to solve UAV path planning problems, but each approximate solution has its own advantages and disadvantages. For example, ant colony algorithm easily falls into the local optimum in the process of realizing path planning. In order to prevent too low pheromones on the longer path and too high pheromones in the shorter path, the upper and lower limits of pheromones as well as their volatile factors are set to avoid falling into the local optimum. Secondly, multi-heuristic factors are introduced, and the overall length of the path serves as an adaptive heuristic function factor that determines the probability of state transition, which affects the probability of ants choosing the corresponding path. The experimental results show that the path length planned by the improved algorithm is 93.6% of the original algorithm, and the optimal path length variance is only 14.22% of the original algorithm. The improved ant colony algorithm shortens the optimal path length and solves the UAV path planning problem in terms of local optima. At the same time, multiple enlightening factors are introduced to increase the suitability of UAV for complex environments and improve the performance of UAV.

CeVO4-V2O3 composites were prepared by simple hydrothermal method, and the effects of ethylene glycol(EG) on the products were studied by XRD, N2 adsorption–desorption, SEM, EDS, XPS, PL and UV-vis spectra. The characterization reveals a slight decrease in surface area and a slight enhancement of visible light absorption in the final sample, while the crystalline phase, morphology and separation efficiency of the collective carriers are severely affected by the EG. At the same time, the photocatalytic effect of CeVO4-V2O3 composites was evaluated by the degradation rate of methylene blue (MB) under simulated visible light. The sample for 10 mL EG obtained the highest efficiency of 96.9%, while the one for 15 mL EG showed the lowest efficiency of 67.5% within 300 min. The trapping experiments and ESR experiment showed that the contribution of active species to the photocatalytic degradation of MB was ∙OH > h+ > ∙O2− in descending order, and a possible degradation mechanism was proposed.

Lingzhu Wen,1,* Guochun Zhang,1,* Chongyang Ren,1,* Xuerui Li,1 Hsiaopei Mok,1 Minghan Jia,1 Yulei Wang,1 Bo Chen,1 Kai Li,1 Li Cao,1 Cheukfai Li,1 Weikai Xiao,1 Jianguo Lai,1 Jiali Lin,1 Guangnan Wei,1 Yingzi Li,1 Yuchen Zhang,1 Xiaoqing Chen,2 Ning Liao1 1Department of Breast Cancer, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Guangzhou, Guangdong, People’s Republic of China; 2Department of Breast Surgical Oncology, Foshan Maternity and Children’s Healthcare Hospital Affiliated to Southern Medical University, Foshan, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ning LiaoDepartment of Breast Cancer, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), No. 106, Zhongshan 2nd Road, Yuexiu District, Guangzhou, Guangdong, People’s Republic of ChinaTel/Fax +86 20-83827812Email syliaoning@scut.edu.cnPurpose: This study aimed to investigate AKT gene mutation status in Chinese breast cancer patients.Methods: The study included 411 breast cancer patients hospitalized in Guangdong Provincial People’s Hospital (GDPH) from June 1, 2017 to September 27, 2018. Mastectomy or breast conserving surgery was performed, and tissue samples were subjected to next-generation sequencing (NGS) to determine AKT gene mutation status. Meanwhile, the expression of human epidermal growth factor receptor 2 (Her2), progesterone receptor (PR), and estrogen receptor (ER) was analyzed by immunohistochemistry staining. The Cancer Genome Atlas (TCGA) database was used for comparative studies.Results: Patients in the GDPH cohort had an older age (P < 0.001), higher postmenopausal rate (P < 0.001), larger tumor size (P < 0.001), higher histologic type of infiltrating duct cancer (P < 0.001), higher metastatic rate (P < 0.001), higher expression of ER (P = 0.015) and HER2 (P < 0.001), and higher percentage of the HR/HER2 subtype (P < 0.001) than those in the TCGA cohort. The GDPH cohort displayed lower rates of overall AKT and AKT3 mutation (P < 0.001), but a higher AKT1 mutation rate (P < 0.0001) compared with the TCGA cohort. Notably, the NGS studies identified missense mutation and copy number amplification as the most common AKT variation type in the GDPH and TCGA cohorts, respectively. Specifically, E17K mutation in AKT1 was predominantly detected in GDPH cohort, while being absent in TCGA cohort. Moreover, in the GDPH cohort, AKT variation was correlated with a number of clinicopathological variables, including age over 50, HER2-, HR+/HER2-, and PR+.Conclusion: Patients in the GDPH cohort had lower rates of AKT and AKT3 mutation and higher AKT1 mutation rate than those in the TCGA cohort, while harboring missense mutations detected predominantly as E17K mutation in AKT1. In GDPH cohort, there were correlations between AKT mutation and the clinicopathological characteristics of patients.Keywords: AKT, next-generation sequencing, breast cancer, somatic mutations, population study

Background Immunotherapies such as PD-L1 inhibitors have shown promising efficiency in breast cancer (BC) patients. However, treatment responses for immunotherapies are diverse since the immunogenicity of breast cancer is heterogeneous. Specific subtypes such as hormone receptor (HR)-positive, human EGF receptor 2 (HER2)-positive, and triple-negative breast cancer (TNBC) have shown heterogeneity in immunogenicity. Therefore, precisely identification of patients potentially benefit from immunotherapy is important. Previous studies have proved PD-L1 expression and tumor mutational burden (TMB) as predictive biomarkers for immunotherapy. Here, we report the PD-L1 expression and TMB status in Chinese BC patients with different subtypes. Using comprehensive molecular analysis, we also characterized the genomic features related to these biomarkers. Methods Tumor samples from 112 Chinese patients with BC were collected and subjected to next-generation sequencing (NGS) and immunohistochemical (IHC) analysis. NGS were performed in a laboratory accredited by College of American Pathologists (CAP) and certified by Clinical Laboratory Improvement Amendments (CLIA) using validated panel targeting 450 cancer genes. Genomic alterations, included including single base substitution, short and long insertions/deletion (Indel), copy number variation, gene fusion, and rearrangement, were assessed. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. Tumor tissues were analyzed for PD-L1 expression by IHC with 22C3 or 28-8 antibodies, respectively. Results The 112 Chinese BC patients consisted of 87 HR+ (77.7%), 19 TNBC (17.0%) and 6 HR-/ HER2 + (5.3%), with a median age of 47.5 years old (range 24-81). Of all patients, 42.0% were positive for PD-L1 expression (CPS≥1), including 30.4% PD-L1 (1≥CPS>10) and 11.6% PD-L1 (CPS≥10). PD-L1 expression were observed in HR+ BCs (41.4%) as well as in TNBC (47.4%) and HR-/ HER2+ (33.3%) subtypes, no significant difference were observed among the three subtypes. 8.9% patients were TMB-High (≥10 muts/Mb) with median TMB of 3.4 muts/Mb (range 0-80.8). TMB was slightly correlated with PD-L1 expression (Kendall tau = 0.241; P =0.01). 17.0% of PD-L1 positive patients and 3.1% of PD-L1 negative patients were TMB-High (p=0.016). Patients with PD-L1 CPS≥10 had significantly higher median TMB (7.1 vs. 3.1 muts/Mb, p Conclusion Our data shows that the PD-L1 expression has no significant difference among HR+, TNBC and HR-/ HER2+ subtypes. These data provide the hypothesis that PD-L1 expression positive in different subtype breast cancers may benefit from immune treatment, including HER2 and Luminal subtypes. Otherwise, there was a correlation between PD-L1 expression and TMB, High TMB was also observed in PD-L1 negative patients, which may enrich the subgroup of patients who could benefit from immunotherapy. The verification of integrated predictive biomarkers for immunotherapy in BC is further needed. Citation Format: Ning Liao, Cao Li, Jundong Wu, Bo Chen, Guochun Zhang, Xueri Li, Liping Guo, Guangnan Wei, Jiali Lin, Yingzi Li, Yuchen Zhang, Hsiaopei Mok, Chongyang Ren, Yulei Wang, Kai Li, Cheukfai Li, Lingzhu Wen, Minghan Jia, Tengjiao Lin, Chunyan Cheng. Pd-l1 expression among different subtypes of chinese breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS17-44.

Purpose Somatic alteration of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is a crucial therapeutic target in breast cancer (BC) and PI3Kα-specific inhibitor Alpelisib has been used in clinics. This study investigates the PIK3CA alterations in Chinese and Caucasians BC patients for the purpose of selecting anti-PI3K therapy. Methods The molecular profile of the PIK3CA gene was analyzed in 412 Chinese patients with untreated invasive BC using a 540 gene next-generation sequencing panel. The results were compared with data of the Caucasian BC patients in The Cancer Genome Atlas (TCGA-white). Results PIK3CA alterations were frequently found in BC of estrogen receptor (ER) positive (49.3%, p = 0.024), low ki67 proliferation index (58.3%, p = 0.007) and low pathological grade (grade I/II/III 80%, 53.4%, 35.9%, p p p = 0.01). Across four molecular subtypes, ER + /human epidermal growth factor receptor 2 positive (HER2 +) tumors harbored the most PIK3CA alterations (51.6%), while ER-/HER2- harbored the least alteration (30.0%) but the most copy number amplification (19.05%). Conclusion PIK3CA alterations prevail in Chinese BC patients and have different molecular features compared to that of Caucasians. The results provide precise annotations of PIK3CA genomic alterations of Chinese in the context of application of PIK3CA inhibitor.

HER2-positive breast cancer is a biologically and clinically heterogeneous disease. Based on the expression of hormone receptors (HR), breast tumors can be further categorized into HR positive and HR negative. Here, we elucidated the comprehensive somatic mutation profile of HR+ and HR− HER2-positive breast tumors to understand their molecular heterogeneity. In this study, 64 HR+/HER2+ and 43 HR-/HER2+ stage I-III breast cancer patients were included. Capture-based targeted sequencing was performed using a panel consisting of 520 cancer-related genes, spanning 1.64 megabases of the human genome. A total of 1119 mutations were detected among the 107 HER2-positive patients. TP53, CDK12 and PIK3CA were the most frequently mutated, with mutation rates of 76, 61 and 49, respectively. HR+/HER2+ tumors had more gene amplification, splice site and frameshift mutations and a smaller number of missense, nonsense and insertion-deletion mutations than HR-/HER2+ tumors. In KEGG analysis, HR+/HER2+ tumors had more mutations in genes involved in homologous recombination (P = 0.004), TGF-beta (P = 0.007) and WNT (P = 0.002) signaling pathways than HR-/HER2+ tumors. Moreover, comparative analysis of our cohort with datasets from The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium revealed the distinct somatic mutation profile of Chinese HER2-positive breast cancer patients. Our study revealed the heterogeneity of somatic mutations between HR+/HER2+ and HR-/HER2+ in Chinese breast cancer patients. The distinct mutation profile and related pathways are potentially relevant in the development of optimal treatment strategies for this subset of patients.

Background: Next generation sequencing (NGS) and the according target-based precision therapy has shown promising efficacy in many tumors. Here we report the genomic characteristics of Chinese breast cancer to support the development of more precise treatment strategy. Methods: Formalin fixed, paraffin embedded (FFPE) tumor samples and matched peripheral blood samples of 220 Chinese cancer patients including 218 females and 2 males were collected for NGS-based 450-genes panel assay. Pathological subtypes included 104 HR+/HER2-, 30 HR-/HER2+, 44 HR+/HER2+ and 42 triple negative breast cancers (TNBC). Assessed genomic alterations included single base substitution, short and long insertions/deletion, copy number variation, gene fusion and rearrangement. MSK breast cancer data was obtained from cBioPortal for comparing the difference between Chinese and Western patients. Results: The top mutated genes were TP53 (88.1%), PIK3CA (26.2%) and PTEN (21.4%) in TNBC; ERBB2 (86.7%), TP53 (86.7%), CDK12 (80.0%) and PIK3CA (23.3%) in HR-/HER2+ patients; ERBB2 (75%), TP53 (61.4%), CDK12 (54.5%) and PIK3CA (45.5%) in HR+/HER2+ patients. In HR+/HER2- patients, the most frequently mutated genes was PIK3CA (49.0%), followed by TP53 (30.8%) and GATA3 (27.9%), whereas the frequency of PIK3CA and GATA3 mutation were lower (41.6% and 19%, respectively) in Western patients. Although Alpelisib was approved by FDA in PIK3CA mutated HR+/HER2- patients, we observed PIK3CA mutation frequency had no difference among four subtypes. In this cohort, patients with PIK3CA mutation were significantly elder than patient without PIK3CA mutation (50 vs 47 years old, p=0.006). The hotspot mutations of PIK3CA (E542X, E545X and H1047X) accounted for 79.8% of PIK3CA mutations (71/89). Gene fusion/rearrangement was observed in 26% patients, in which 4 patients had gene fusions. Gene variations in homologous recombination pathway were found in 27.7% of patients. Among the 11.4% of patients with BRCA1/2 mutations, 11 patients harbored germline mutations and 19 patients had somatic mutations. Rearrangement accounted for 35% in somatic BRCA1/2 mutations. In the patients with germline BRCA1/2 mutation, 6 were HR+/HER2- patients who have been approved to use Olaparib. Based on the usage of CDK4/6 inhibitor in HR+/HER2- patients, this 450-genes panel enabled us to find that 41.3% HR+/HER2- patients had genes variations are related to CDK4/6 inhibitor resistance (CCND1, 18.3%; FGFR1 17.3%; NF1, 7.7%; MDM2, 6.7%; ESR1, 6.7% and RB1, 1.9%). The median TMB was 4.3 Muts/Mb in the whole cohort and patients with KMT2C mutations had significantly higher TMB (5.5 vs 3.8 Muts/Mb, p=0.004). In addition, Chinese breast cancer patients had a significantly higher frequency of KMT2C mutations compared to western patients (11.4% vs 1.4%, p Citation Format: Ning Liao, Guochun Zhang, Bo Chen, Yulei Wang, Kai Li, Chongyang Ren, Hsiaopei Mok, Li Cao, Lingzhu Wen, Minghan Jia, Cheukfai Li, Liping Guo, Guangnan Wei, Jiali Lin, Jiangguo Lai, Honglin Guo, Wenjing Wang, Shiyue Zhang, Zhijian Song, Jian Wang, Hui Chen, Jinwei Hu, Weifeng Wang, Weiwei Shi, Kai Wang. Comprehensive genomic analysis of Chinese breast cancer and clinical application [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-07-03.

Background MYC is frequently amplified and its amplification is associated with poor prognosis in breast cancer patients. This study aimed to determine the prevalence of MYC alterations from Chinese patients, the correlations between MYC amplification and clinicopathological characteristics, as well as its impacts on patient outcomes in breast cancer patients. Methods We analyzed 412 cases of breast cancer specimens in Guangdong Provincial People's Hospital (GDPH) for MYC alterations from June 1, 2017 to September 27, 2018, using next generation sequencing. The associations between MYC amplification and clinicopathological characteristics were determined using chi square. We further compared the our results with those from The Cancer Genome Atlas (TCGA) cohort (n=1079). Kaplan-Meier curves were drawn to determine the impacts of MYC amplification on patient outcomes. Results MYC was amplified in 12.44% (51/410) in GDPH cohort and the mean copy number of our cohort was 4.42 (2.84-11.27), while the frequency of MYC amplification in TCGA cohort was much higher (21.22%, 229/1079). Except that, we also found two fusions. Among these, one was RTFDC1-MYC fusion (AF=1.62%) and the other was PVT1-MYC fusion (AF=3.33%). The case with PVT1-MYC fusion was also found to have PVT1-MYC co-amplification concurrently. In TCGA cohort, we found MYC amplification to be associated with age (P=0.047), tumor type (P=0.000), ER status (P=0.000), PR status (P=0.000), HER2 status (P=0.008) and molecular subtype (P=0.000). Whereas, except for molecular subtype (P=0.028), we only found MYC amplification to be associated with tumor size (P=0.023) and Ki-67 (P=0.031) in GDPH cohort. According to the survival information from TCGA, patients with MYC amplification had significantly inferior overall survival (OS) in both triple negative breast cancer (TNBC) (P=0.02) and HR+/HER2+ breast cancer patients (P=0.03). Conclusions This study evaluated the differences of MYC mutations in Chinese and and TCGA cohort breast cancer patients. Except for MYC amplification, we found two rare fusions. Results showed MYC amplified less frequently in Chinese patients and was associated with inferior OS in both TNBC and HR+/HER2+ breast cancer patients. We suggest further research with expand the sample size is necessary to draw the ethnical differences of MYC mutations. Citation Format: Li Cao, Guochun Zhang, Yulei Wang, Bo Chen, Chongyang Ren, Lingzhu Wen, Liping Guo, Kai Li, Minghan Jia, Ning Liao. Associations between MYC alterations and clinical pathological characteristics in Chinese patients and TCGA cohort [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-08-22.

Purpose: Somatic alterations of PIK3CA gene is an important therapeutic target in breast cancer (BC). The PI3Kα-specific inhibitor alpelisib was remarkably active against PIK3CA-mutated, HR-positive/HER2-negative BC in the SOLAR-1 trial. We hypothesized that PIK3CA alterations in Chinese BC patients across different molecular subtypes might differ from other ethnic groups and this information would be useful for selecting anti-PI3K therapy. Methods: The molecular profile of the PIK3CA gene was analyzed in 412 Chinese untreated invasive BC patients with ER/HER2 molecular subtypes, using a 540 gene next-generation sequencing panel. The results were compared to the molecular profile of Caucasian breast cancer patients in The Cancer Genome Atlas(TCGA-white). Results: Compared to wild type, PIK3CA alterations were more frequent in the ER+ subtype (49.3%, p=0.024), and tumors with low ki67 proliferation (58.3%, p=0.007) and low histological grade (grade I/II/III 80%, 53.4%, 35.9%, p Citation Format: Minghan Jia, Ning Liao, Bo Chen, Guochun Zhang, Yulei Wang, Xiaoqing Chen, Liping Guo, Li Cao, Hsiaopei Mok, Chongyang Ren, Kai Li, Cheukfai Li, Lingzhu Wen, Jiali Lin, Guangnan Wei, Zhou Zhang, Charles M Balch. PIK3CA somatic alterations in 412 chinese invasive breast cancers: Higher frequency of mutant H1047R detected by next generation sequencing compared to breast cancer in caucasians [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-09-11.

The survival benefits of recurrent laryngeal nerve lymph node dissection (RLNLD) in esophageal squamous cell carcinoma (ESCC) are still under debate, and the prognostic value of unilateral RLNLD has been rarely studied. Therefore, the aim of the present study was to investigate the clinical significance and outcomes of RLNLD in ESCC in a large-scale cohort study, to shed light on the outcomes of unilateral RLNLD, and to identify the factors that affect the prognostic outcome of RLNLD.We retrospectively reviewed 1153 patients with thoracic ESCC who underwent right thoracotomy with lymphadenectomy. The impact of RLNLD on disease-free survival (DFS) and overall survival (OS) was estimated using the Kaplan-Meier method and Cox proportional hazard models. Inverse probability of treatment weighting (IPTW) was performed to adjust for differences in baseline variables in pairwise comparisons. Subgroup analysis of survival and postoperative complications was conducted for selective RLNLD.RLN lymph node (LN) metastasis was independently associated with tumor location and most other LN station metastases. RLNLD was an independent prognostic factor for DFS and OS. Both patients who underwent unilateral and bilateral RLNLD had significantly better DFS and OS than the non-RLNLD patients. Furthermore, pairwise comparisons with IPTW confirmed these results, and we found that patients who underwent bilateral RLNLD had better survival than those who underwent unilateral RLNLD. However, subgroup analysis showed that there was no survival benefit and higher morbidity after bilateral RLNLD for patients with cancer in the lower thoracic esophagus, and elderly and female patients.RLN LN metastasis is very frequent in ESCC, and both unilateral and bilateral RLNLD have considerable survival benefits. Selective RLNLD with better survival and lower morbidity was recommend for some defined subgroups.

Background HER2-low breast cancers were reported to have distinct clinicopathological characteristics from HER2-zero; however, the difference in their genetic features remains unclear. This study investigated the clinical and molecular features of breast tumors according to HER2 status. Methods We analyzed the clinicopathological and genomic data of 523 Chinese women with breast cancer. Genomic data was generated by targeted next-generation sequencing (NGS) of breast tumor samples using a commercial 520 gene panel. The cohort was stratified according to HER2 status as HER2-zero (n = 90), HER2-low (n = 231), and HER2-positive (n = 202) according to their immunohistochemistry and fluorescence in situ hybridization results. Results HER2-low breast tumors were enriched with hormone receptor-positive tumors, and who had lower Ki67 expression levels. Genes were differentially mutated across HER2 subgroups. HER2-low tumors had significantly more mutations involved in PI3K-Akt signaling than HER2-positive (p < 0.001) and HER2-zero breast tumors (p < 0.01). HER2-zero tumors had more mutations in checkpoint factors (p < 0.01), Fanconi anemia (p < 0.05), and p53 signaling and cell cycle pathway (p < 0.05) compared to HER2-low breast tumors. Compared with HER2-zero tumors, HER2-low tumors had significantly lower pathological complete response rates after neoadjuvant therapy (15.9% vs. 37.5%, p = 0.042) and proportion of relapsed/progressed patients across follow-up time points (p = 0.031), but had comparable disease-free survival (p = 0.271). Conclusion Our results demonstrate the distinct clinical and molecular features and clinical outcomes of HER2-low breast tumors.

Background: Human intestinal tract microbiome dysbiosis plays an emerging pivotal role in tumorigenesis of gastrointestinal tract cancers. For esophageal squamous cell carcinoma (ESCC), the esophageal microbiota plays a critical role during the pathogenesis. The microbiome of esophageal can impact its host decades before the onset of ESCC, and can interact with the host’s physiological situation, which are affected by lifestyle factors, including diet, obesity, alcohol and tobacco use, and oral hygiene.Our objective is to analyze the composition of the ESCC-associated microbiota and characterize its contribution to the development of ESCC. The esophageal microbiota was prospectively investigated in 18 patients with ESCC and 11 patients with physiological normal (PN) esophagus by 16S rRNA gene profiling, using next-generation sequencing. Results: The microbiota composition in tumor tissues of ESCC patients is significantly different from that of patients with PN tissues. The ESCC microbiota was characterized by reduced microbial diversity, by decreased abundance of Bacteroidetes, Fusobacteria and Spirochactes. Employing these taxa into a microbial dysbiosis index demonstrated that dysbiosis microbiota had good capacity to discriminate between ESCC and PN esophagus. Functional analysis of the microbiota characterized that ESCC microbiota had altered nitrate reductase and nitrite reductase functions when compared with PN group. The observations were confirmed in other validation cohorts.Conclusions: Detailed analysis of the microbiota of the ESCC patients revealed that tumor exhibit a dysbiotic microbial community when compared with PN groups. We characterized microbial compositional changes, and further identified significant enrichments of Treponema amylovorum, Streptococcus infantis, Prevotella nigrescens, Porphyromonas endodontalis, Veillonella dispar, Aggregatibacter segnis, Prevotella melaninogenica, Prevotella intermedia, Prevotella tannerae, Prevotella nanceiensis and Streptococcus anginosus in ESCC oncogenic progression.Trial registration number: This study was registered at the Chinese Clinical Trial Registry (ChiCTR1800018897). http://www.chictr.org.cn/.

There are enormous types of traffic flows in the IoT era. The traffics could be control by Software Defined Network (SDN) or other transmission protocols in the core networks or mobile edge networks. TCP-BBR algorithm has a better performance on long-fat pipes than traditional TCP protocols in terms of link perception and response time. However, when TCP-BBR and other congestion control algorithms which are based on time delay like TCP-Westwood is applied to the same network links, TCP-BBR will perform unfriendly to the TCP-Westwood. Aiming to improve the fairness between TCP-BBR congestion control algorithm and delay-based congestion control algorithms, this paper proposes a congestion control algorithm based on TCP-BBR which has moderate fairness named Modest Fairness BBR(MFBBR). The simulation results on the Mininet show that our algorithm can improve the fairness of BBR when it coexists with Westwood, and it also has better fairness than delay-based congestion control algorithms.

The application of circulating tumor DNA (ctDNA) monitoring after resection in pathologic(p) stage I lung adenocarcinoma (LUAD) patients remains controversial and it is of great clinical interest to decipher the difference of genetic features between ground-glass opacity (GGO) and solid nodules (non-GGO) subgroups. We aim to assess the utility of ctDNA in tracking early recurrence or metastasis following surgery and reveal the genetic differences between GGO and non-GGO.Tumor tissues and matched postoperative plasma samples were collected from a total of 82 (p)stage I LUAD patients. Comprehensive genomic profiling was performed using capture-based hybrid next generation sequencing by targeting 422 cancer relevant genes.EGFR and TP53 represent commonly mutated genes in this cohort of (p)stage I lung adenocarcinoma, followed by alterations in ALK, PIK3CA, STK11 and MYC. For a median follow-up period of 22.83 months after surgery, 65 out of 67 ctDNA-negative patients remained progression-free, while 3 out of 15 ctDNA-positive patients progressed [P = 0.040; positive predictive value = 0.20, 95 % confidence interval (CI), 0.04-0.48; negative predictive value = 0.97, 95 % CI, 0.9-1]. With time-dependent Cox regression analysis, we observed that ctDNA positivity significantly correlated with increased probability of early tumor recurrence or metastasis (P = 0.02, HR=8.5). Further comparison between GGO and non-GGO subgroups indicated the frequency of TP53 mutations in non-GGO was markedly higher than that in GGO (47 % vs 21 %, P 0.05). Pathway analysis showed the epigenetic regulation pathway was more frequently affected in GGO subgroup, while impaired apoptosis/cell cycle pathway was more enriched in non-GGO LUADs.Our longitudinal ctDNA monitoring data showed that undetectable ctDNA may predict low risk of tumor recurrence or metastasis in postoperative (p)stage I LUAD patients, while it requires further investigation on how robust the positive ctDNA results could predict tumor relapse in these patients.NCT03172156.

Purpose Despite the therapeutic success of existing HER2-targeted therapies, tumors respond quite differently to them. This study aimed at figuring out genetic mutation profile of Chinese HER2-positive patients and investigating predictive factors of neoadjuvant anti-HER2 responses. Methods We employed two cohorts. The first cohort was comprised of 181 HER2-positive patients treated at Guangdong Provincial People’s Hospital from 2012 to 2018. The second cohort included 40 patients from the first cohort who underwent HER2-targeted neoadjuvant chemotherapy. Genetic mutations were characterized using next-generation sequencing. We employed the most commonly used definition of pathological complete response (pCR)-eradication of tumor from both breast and lymph nodes (ypT0/is ypN0). Results In Chinese HER2-positive breast cancer patients, TP53 (74.6%), CDK12 (64.6%) and PIK3CA (46.4%) have the highest mutation frequencies. In cohort 2, significant differences were found between pCR and non-pCR groups in terms of the initial Ki67 status, TP53 missense mutations, TP53 LOF mutations, PIK3CA mutations and ROS1 mutations (p = 0.028, 0.019, 0.005, 0.013, 0.049, respectively). Furthermore, TP53 LOF mutations and initial Ki67 status (OR 7.086, 95% CI 1.366–36.749, p = 0.020 and OR 6.007, 95% CI 1.120–32.210, p = 0.036, respectively) were found to be predictive of pCR status. Conclusion TP53 LOF mutations and initial Ki67 status in HER2-positive breast cancer are predictive of pCR status after HER2-targeted NACT.

Volatile organic compounds (VOCs), such as toluene, have aroused wide concerns its emissions growth and harmfulness. Catalytic oxidation has been considered as one of the most efficient technologies for toluene degradation. In this work, MOF-derived CeO2 supported Ag catalysts were prepared by different synthesis method. Toluene oxidation test found that Ag-Ce-BTC-C synthesized by one-pot and calcination at 500 °C under Ar and O2 atmosphere exhibited the better catalytic performance for toluene oxidation (T90 = 226 °C). H2 temperature programmed reduction and X-ray photoelectron spectroscopic results exhibited that the preparation method had a great influence on the physicochemical properties of the supported Ag catalysts. The better catalytic performance was attributed to the better reducibility, more active oxygen species and oxygen vacancies, higher molar ratio of Oads/Olat, Ce3+/Ce4+ and Ag0/Agδ+. This work has a certain guiding significance for the preparation of highly active MOF-derived supported catalysts.

The data on the phenotypes associated with some rare germline mutations in Chinese breast cancer patients are limited. The difference in somatic mutation profiles in breast cancer patients with germline BRCA and non-BRCA mutations remains unexplored. We interrogated the germline and somatic mutational profile of 524 Chinese breast cancer patients with various stages unselected for predisposing factors using a panel consisting of 520 cancer-related genes including 62 cancer susceptibility genes. We divided the patients into three groups according to germline mutations: Germline-BRCA1/2, Germline-others (non-BRCA) and Others (non-carriers). A total of 58 patients (11.1%) carried 76 likely pathogenic or pathogenic (LP/P) germline variants in 15 cancer predisposition genes. Germline BRCA1/2 mutations were detected from 29 (5.53%) patients; with 11 (2.10%) BRCA1 carriers and 18 (3.44%) BRCA2 carriers. In addition, LP/P germline mutations were detected in other genes including MUTYH (n=4), PALB2 (n=4), ATM (n=3), BRIP1 (n=3), CDH1 (n=3), RAD51C (n=3), CHEK2 (n=2), FANCA (n=2), PMS2 (n=2), TP53 (n=2), FANCI (n=1), FANCL (n=1) and PTEN (n=1). At least one variant of uncertain significance (VUS) was identified in 490 (93.5%) patients. Young age (P=0.011), premenopausal status (P=0.013), and breast/ovarian cancer family history (P=0.001) were correlated with germline mutations. Germline-BRCA1/2 group was detected with more missense (P=0.02) and less copy-number amplification (P=0.04) than Germline-others group. Meanwhile, Germline-others group and Others group are very similar (P>0.05). The mutation rates of AKT1, CCND1, FGFR1, and PIK3CA were different among the three groups. By investigating all breast and ovarian cancer-related genes listed in the US genetic guidelines, we identified 15 cancer susceptibility genes frequently mutated in the germline of our population and must be included in cancer predisposition screening. Our study contributed a better understanding of the tumor characteristics of patients with LP/P germline mutations.

BACKGROUND: The complexity of breast cancer at the clinical, morphological and genomic levels has been extensively studied in the western population. However, the mutational genomic profiles in Chinese breast cancer patients have not been explored in any detail. METHODS: We performed targeted sequencing using a panel consisting of 33 breast cancer-related genes to investigate the genomic landscape of 304 consecutive treatment-naïve Chinese breast cancer patients at Guangdong Provincial People’s Hospital (GDPH), and further compared the results to those in 453 of Caucasian breast cancer patients from The Cancer Genome Atlas (TCGA). RESULTS: The most frequently mutated gene was TP53 (45%), followed by PIK3CA (44%), GATA3 (18%), MAP3K1 (10%), whereas the copy-number amplifications were frequently observed in genes of ERBB2 (24%), MYC (23%), FGFR1 (13%) and CCND1 (10%). Among the 8 most frequently mutated or amplified genes, at least one driver was identifiable in 87.5% (n=267) of our GDPH cohort, revealing the significant contribution of these known driver genes in the development of Chinese breast cancer. Compared to TCGA data, the median age at diagnosis in our cohort was significantly younger (48 vs. 58 years; P

With the fast development of IoT network, there are more and more images generated by sensors and other devices, which increases the transmission expenses. By adopting image steganography, the images can deliver more information than they could. Therefore, the transmission expenses could be significantly reduced. However, the safety and quality of steganographic algorithms is not promising nowadays. To improve this situation, we propose an SVM-based steganography algorithm. The algorithm takes advantage of four features, including the variance of the image, the overall difference, the shape context matching and the smoothness. The analysis and experimental results show that the information hiding algorithm can effectively optimize the information steganography and anti-steganography analysis, which could be used in IoT.

Flower-like ZnO microspheres with high uniformity have been successfully fabricated by a simple hydrothermal method without surfactants. The effect of hydrothermal reaction time on the morphologies of the resulting products is investigated. The structural properties were systematically investigated by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The formation process of flower-like ZnO microspheres is discussed. Finally, flower-like ZnO microspheres show significantly improved photocatalytic activity for the degradation of Methylene blue (MB) as compared to commercial ZnO.

N6-methyladenosine (m6A) is a common RNA modification on eukaryotic mRNA and several m6a regulatory proteins, which plays a crucial part in breast cancer. But the copy number variations (CNVs) for m6a regulatory proteins and their role in pathogenesis and progression in breast cancer is still unclear. By analyzing the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and the cancer genome atlas (TCGA database), we screened CNVs of ten m6A regulatory genes, including YTHDF3, YTHDF1, FTO, YTHDC1, ALKBH5, METTL3, WTAP, METTL14, YTHDF2, YTHDC2. Among them, YTHDF3 and YTHDF1 amplification had higher alteration rates among ten m6A regulatory genes. YTHDF1 and YTHDF3 amplification resulted in higher mRNA expression (P Univariate and multivariate Cox proportional hazard analysis for 10-year overall survivalUnivariateUnivariateHR95% CIP valueHR95% CIP valueNode status1.7181.566-1.885 Citation Format: Cheukfai Li, Guochun Zhang, Yulei Wang, Bo Chen, Kai Li, Li Cao, Chongyang Ren, Lingzhu Wen, Minghan Jia, Hsiaopei Mok, Jianguo Lai, Weikai Xiao, Xuerui Li, Ning Liao. YTHDF1 amplification associates with clinicopathological featuresand predicts worse survival in breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5912.

552 Background: Extensive efforts by The Cancer Genome Atlas (TCGA) Network had provided much of our current understanding of the molecular profile of various solid tumors including breast tumors; however, Asian patients were underrepresented in this cohort. In this study, we aimed to elucidate the comprehensive genetic alteration profile of early-stage breast tumors among Chinese patients. Methods: Surgical tissue samples from 589 Chinese women with stage I-III breast cancer with various histology and molecular subtype consecutively diagnosed at Guangdong Provincial People’s Hospital were sequenced using a panel targeting 520 cancer-related genes spanning 1.64Mb of the human genome. Clinical and genomic data from our cohort was compared with publicly-available data from 1,046 stage I-III breast cancer patients from the TCGA dataset. Results: Based on the analysis of the genetic alteration profile from our cohort, at least one genetic alteration was observed from 98% of the tumor samples, with TP53 (47%), PIK3CA (45%), ERBB2 (30%), and CDK12 (18%) as the most commonly altered genes. The most common genetic alteration types were copy number amplification (43.6%) and missense mutations (36.8%). As compared with the TCGA dataset, our cohort is mostly composed of women 50 years and younger (59.1% vs. 30.4%, P< 0.001), with significantly fewer patients with lobular carcinoma histology (2.4% vs. 19.0%, P< 0.001), and significantly more patients with pathologic stage I tumors (23.3% vs. 17.3%, P= 0.012). Consistently, genetic alterations detected from our cohort affected genes involved in PI3K (63% vs. 56%, P= 0.009) and cell cycle (23% vs. 35%, P< 0.001) pathways, with statistically different genetic alteration rates as compared with the TCGA dataset. Comparison of genetic alteration profile between the two cohorts revealed that our cohort had more frequent genetic alterations in genes including PIK3CA ( P< 0.001), TP53, particularly in hotspot mutations Q192* ( P< 0.001) and A307V/del ( P= 0.02), and ERBB2 amplification ( P< 0.001). Conclusions: Our study contributes to the understanding of the key pathways and specific genetic alterations harbored by Chinese patients with early-stage breast cancer that could potentially be developed as markers of treatment response to targeted therapeutics.

553 Background: HER2 expression or amplification qualify patients to receive targeted therapeutics against HER2; however, traditional methods of quantifying HER2 amplification using fluorescence in situ hybridization (FISH) do not include a reliable definition for low level amplification. With the promising response rate of patients with low HER2 amplified-metastatic breast cancer to subsequent-line trastuzumab deruxtecan (DS-8201a) therapy, there is a need to improve the existing criteria to accurately identify patients with low HER2. In our study, we investigate whether HER2 amplification quantified by NGS could provide a method to stratify patients into subgroups. Methods: A total of 774 patients diagnosed with breast cancer from Guangdong Provincial People's Hospital (GDPH) who underwent targeted NGS using 520 or 33 cancer-related genes and had their HER2 status evaluated with either FISH or IHC were included in this study. HER2 status were defined as per 2018 ASCO/ACP guidelines. Results: Our results demonstrate that NGS could quantify HER2 amplification with high sensitivity and specificity, with area under the curve of 0.990 [95%CI: 0.982-0.999]. The receiver operating curve indicated an optimal cut-off of 2.62 copy number (CN) for identifying IHC/FISH HER2-negative status with 97.8% specificity. Meanwhile, the cut-off of ≥ 3.62 CN identified patients with IHC/FISH HER2-positive status with 99.8% specificity. Among the 774 patients, 65.8% (n = 509) had HER2 CN of ≤ 2.62 and were classified as HER2 non-amplified, while 25.8% (n = 199) had HER2 CN of ≥ 3.62, classified as HER2-amplified. The remaining 66 patients (8.5%) had HER2 CN between 2.62 and 3.62, and were the patients with heterogeneous IHC/FISH results, classified using NGS as HER2 low-amplified. Patients with low-amplified (49.0% vs. 38.8%, P < 0.001) and amplified (50.3% vs. 38.8%, P < 0.001) HER2 had significantly more number of copy number amplifications in other gene, including CDK12, RARA, and SPOP (P < 0.001, P < 0.001) than patients with HER2 non-amplified, indicating distinct mutation profile. Conclusions: Our results demonstrate that NGS could provide a more accurate stratification of patients based on their HER2 amplification levels. Patients with low levels of HER2 amplification has a distinct mutation profile, suggesting that NGS could serve as a robust tool to identify patients with HER2 amplification, whether high or low, who could benefit treatment with targeted agents designed against heterogeneous HER2 expression.

3537 Background: Pathologic(p)stage I lung adenocarcinoma (LUAD) patients exhibit high levels of genetic heterogeneity and the association between the genomic characteristics of (p)stage I LUADs and tumor recurrence remains poorly understood. Circulating tumor DNA (ctDNA) monitoring after resection represents a useful tool to predict response to therapy and tumor recurrence but its application in (p)stage I LUAD patients remains controversial. In addition, it is of great clinical interest to decipher the difference of genetic features between ground-glass opacity (GGO) and solid nodules (non-GGO) subgroups. Methods: Tumor tissues and matched post-operative plasma samples were collected from a total of 86 Chinese (p)stage I LUAD patients who were enrolled in a clinical study (NCT03172156). Comprehensive genomic profiling was performed using capture-based hybrid next generation sequencing by targeting 422 cancer relevant genes. Results: EGFR and TP53 represent commonly mutated genes in this cohort of (p)stage I lung adenocarcinoma, followed by alterations in ALK, PIK3CA, STK11and MYC. For a median follow up period of 21.54 months after surgical resection, we observed that ctDNA positivity significantly correlated with an increased probability of early tumor recurrence or metastasis ( P= 0.03, HR = 7.9), and in particular, the EGFR mutation status of ctDNA samples rather than that of primary tumor samples significantly correlated with shorter disease-free survival (DFS). Further comparison between GGO and non-GGO subgroups indicated that the frequency of TP53 mutations in non-GGO was markedly higher than that in GGO (48% vs 20%, P< 0.05). In addition, pathway analysis showed that the epigenetic regulation pathway was more frequently affected in the GGO subgroup, while impaired apoptosis/cell cycle pathway was more enriched in the non-GGO LUADs. Conclusions: Our data show that ctDNA positivity, including the EGFR mutation status, significantly correlated with early relapse or metastasis after surgery, representing a useful tool to predict treatment response and tumor relapse in (p)stage I LUAD patients. Mutated TP53 was more abundant in non-GGO comparing to GGO (p)stage I LUADs that may act as potential oncogenic driver in LUAD development and/or disease progression. Clinical trial information: NCT03172156 .

554 Background: Limited studies have investigated the molecular underpinnings driving breast cancer development in Chinese younger women. Based from our previous data, more Chinese women are diagnosed with early-onset breast cancer than in the West. In our study, we aim to investigate the comprehensive mutational profile of Chinese women 35 years old and younger (≤35y) diagnosed with breast cancer. Methods: Targeted sequencing was performed on surgically-removed tumor tissues and blood samples collected from 589 women diagnosed with stage I-III breast cancer of various molecular subtypes at the Guangdong Provincial People’s Hospital (GPDH) using a gene panel interrogating 520 cancer-related genes. We compared the data of 53 women aged ≤35y from our cohort to the data from 33 breast cancer patients aged ≤35y included in The Cancer Genome Atlas (TCGA) dataset. Results: Among the women aged ≤35y with early-stage breast cancer from both cohorts, our cohort had more number of hormone receptor-positive (HR+) patients (GPDH, 72% vs. TCGA, 61%, P< 0.001). Analysis revealed an overall mutation detection rate of 98% in our cohort, with mutations affecting genes involved in the PI3K pathway (47%) and cell cycle pathway (23%). TP53 and PIK3CA were the most commonly mutated genes, with mutation rates of 51% and 25% from our cohort. No statistical difference in mutation profile was found between GPDH and TCGA cohorts. Moreover, germline mutations considered as pathogenic and likely pathogenic (P/LP) in breast cancer susceptibility genes including BRCA1 (n = 4), BRCA2 (n = 2), PALB2 (n = 1), PMS2 (n = 1), PTEN (n = 1), and ATM (n = 1) were detected from 18.9% (10/53) of the patients from our cohort. Women aged ≤35y had significantly more germline BRCA1 mutations than patients > 35y from our cohort (7.5%, 4/53 vs. 2.1%, 11/536 P= 0.049). Conclusions: Our study has identified the involvement of PI3K and cell cycle as the two key pathways in the early development of breast tumors in younger women. In addition, our results also support the role of P/LP germline mutations in breast oncogenesis in Chinese patients with early-onset breast cancer, indicating the need to include a more comprehensive germline mutation screening in our population.

Background: The data on the prevalence of cancer-related germline mutations and the phenotypes associated with some rare mutations in Chinese breast cancer patients are limited. In this study, the mutation profile of a large cohort of unselected Chinese breast cancer patients were elucidated to determine the prevalence of likely pathogenic or pathogenic (LP/P) germline mutations and their association with clinicopathologic features as well as somatic mutations.Methods: To elucidate the genomic and somatic mutation profile of 524 Chinese breast cancer patients with various stages unselected for predisposing factors, targeted sequencing was performed using a panel consisting of 520 cancer-related genes including 62 cancer susceptibility genes for germline profile. To analyze the somatic mutation profile of the germline mutation carriers, the patients were divided into three groups according to germline mutations: BRCA1/2 (Germline-BRCA1/2), non-BRCA1/2 (Germline-others) and germline wild-type (gWT) groups.Results: A total of 58 patients (11.1%) carried 76 LP/P germline variants in 15 cancer predisposition genes. Germline BRCA1/2 mutations were detected in 29 (5.53%) patients; with 11 (2.10%) BRCA1 carriers and 18 (3.44%) BRCA2 carriers. In addition, LP/P germline mutations were detected in other genes including MUTYH (n=4), PALB2 (n=4), ATM (n=3), BRIP1 (n=3), CDH1 (n=3), RAD51C (n=3), CHEK2 (n=2), FANCA (n=2), PMS2 (n=2), TP53 (n=2), FANCI (n=1), FANCL (n=1) and PTEN (n=1). At least one VUS was identified in 490 (93.5%) patients. Young age (P=0.011), premenopausal status (P=0.013), and breast/ovarian cancer family history (P=0.001) were correlated with germline mutations. Furthermore, patients with Germline-BRCA1/2 had significantly more missense mutations (P=0.02) and less copy number amplification (P=0.04) than patients carrying Germline-others. Meanwhile, mutation types were comparable between Germline-others and gWT patients (P>0.05). Furthermore, the somatic mutation rates for AKT1, CCND1, FGFR1 and PIK3CA varied among the three groups. No mutations in AKT1 and CCND1 were detected in the Germline-BRCA1/2 group. FGFR1 mutations were detected in 24% of the Germline-others group, while the Germline-BRCA1/2 and gWT groups had 10% and 9%, respectively. Moreover, PIK3CA mutations was significantly fewer in the Germline-BRCA1/2 group than Germline-Others (P=0.02) and gWT patients (P=0.002).Conclusions: Our study is the largest germline mutation study in unselected breast cancer patients in Southern China interrogating all breast or ovarian cancer-related genes listed in the US genetic guidelines. The inclusion of the 15 most common cancer susceptibility genes in cancer predisposition screening is important in the Chinese population for selecting the subset of breast cancer patients to receive multigene panel testing. Furthermore, our study also revealed the distinct somatic mutations profiles in germline mutation carriers, which contributes for a better understanding of the tumor characteristics of patients with LP/P germline mutations. Citation Format: Ning Liao, Bo Chen, Guochun Zhang, Chongyang Ren, Yulei Wang, Liping Guo, Li Cao, Lingzhu Wen, Kai Li, Minghan Jia, Cheukfai Li, Hsiaopei Mok, Guangnan Wei, Jiali Lin, Zhou Zhang, Ting Hou, Analyn Lizaso, Jing Liu. Comprehensive analysis of the prevalence of germline mutations and their association with somatic mutations in Chinese unselected breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-03-05.

With the development of geographic information system, digital earth and digital city play more and more important roles in life. The data generated by sensors or other edge nodes need to be collected by crawlers in the distributed systems in IoT, such as the GIS data in CyberGIS. In some edge networks, network operators have adopted methods to limit crawlers, such as blocking the request IP addresses, requiring logging in verification codes and other measures to avoid disturbance to servers. To collect data from web servers in these types of edge networks, a dynamic IP address based strategy DP-crawler is proposed to solve the anti-crawler strategies in the edge networks. DP-crawler can dynamic get proper IP addresses from a security-aware list and select the best available proxies. The security-aware list is designed to use the block-chain. Security and dynamic storage can be achieved by this method. DP-crawler is used to crawler webs, and the detailed information of Douban movies are obtained in the experiments. The experiment results show that the DP-Crawler can get more information by using the DP-Crawler.

Background Subclinical hypothyroidism (SCH) and gestational diabetes mellitus (GDM) are common endocrine disorders that occur during pregnancy. Objective To determine whether the risk of GDM differs between pregnant women with normal thyroid function and those with SCH. Search strategy MEDLINE, EMBASE, the Cochrane Library, and Web of Science were searched for studies published in English from inception to March 1, 2017, using combinations of the search terms "thyroid dysfunction", "thyroid diseases", "subclinical hypothyroidism", "hypothyroxinemia", "thyrotropin", "gestational diabetes", "hyperglycemia in pregnancy", and "adverse pregnancy outcomes". Selection criteria We selected cohort studies that included pregnant women with SCH; in which the outcome of interest was, or included, the incidence of GDM; and that had data available for both the SCH and GDM groups. Studies were excluded if assisted reproductive technologies were used to achieve pregnancy; reviews, abstracts, and case reports were also excluded. Data collection and analysis Eleven studies were included in the analysis. Summary odds ratios (ORs) for the risk of GDM were calculated. Main results SCH with positive antithyroid autoantibodies markedly increased GDM risk (OR 3.22, 95% confidence interval 1.72-6.03, I2 =55%). Conclusion SCH with positive antithyroid autoantibodies in pregnancy is associated with an increased risk of GDM.

We aimed to investigate the possible signaling pathways underlying the regulation of grape seed proanthocyanidins extracts (GSPE) on lipid metabolism. One hundred male C57BL/6 mice were divided into four groups: control group (normal diet), GSPE group (normal diet + GSPE), high-fat diet group (HFD), and high-fat diet plus GSPE (200 mg/kg/day) group (HFD + GSPE). Mice received the diets for 180 days. Body weight and serum lipid levels were measured. Autophagic flux characteristics, such as accumulation of lipids, mitochondria, and autophagosomes in the liver, were detected using transmission electron microscopy. Expression profile of microRNAs (miRNAs) in the liver was determined using RNA microarray and quantitative real time polymerase chain reaction (qRt-PCR). GSPE significantly decreased the weight gain, serum levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol but increased high-density lipoprotein cholesterol in the HFD mice. Autophagic flux was significantly increased by HFD but decreased by GSPE treatment. GSPE significantly attenuated HFD-induced miR-96 upregulation, which in turn reduced the expressions of miR-96 downstream molecules, FOXO1, mTOR, p-mTOR, and LC3A/B. These results suggested that the miR-96 is involved in the protective effect of GSPE against HFD-induced dyslipidemia. Possible mechanisms might be through mTOR and FOXO1, which facilitate autophagic flux for clearance of lipid accumulation.