Background: OS is the most common malignant tumor of bone which was featured with osteoid or immature bone produced by the malignant cells, and biomarkers are urgently needed to identify patients with this aggressive disease. Methods: We downloaded gene expression profiles from GEO and TARGET datasets for OS, respectively, and performed WGCNA to identify the key module. Whereafter, functional annotation and GSEA demonstrated the relationships between target genes and OS. Results: In this study, we discovered four key genes—ALOX5AP, HLA-DMB, HLA-DRA and SPINT2 as new prognostic markers and confirmed their relationship with OS metastasis in the validation set. Conclusions: In conclusion, ALOX5AP, HLA-DMB, HLA-DRA and SPINT2 were identified by bioinformatics analysis as possible prognostic markers for OS metastasis.

Background: Gastric cancer (GC) ranks the fifth most common cancer and the fourth most frequent cause of cancer-related deaths. Genomically stable gastric cancers (GSGCs) represent 20% of all GCs and GSGC patients have the worst prognosis among all GC subtypes. Although two HER2-targeted antibody-drug conjugates (ADCs), RC48 and DS8201, have shown promising clinical efficacies, most GSGC patients do not benefit from these ADCs due to the infrequent and heterogeneous HER2 expression. Therefore, there remains a significant and unmet medical need for developing novel ADCs targeting GSGC tumors. Methods: In this presented study, a quantitative and unbiased approach was first used to identify potential targets for GSGC in a panel of human GSGC cell lines in reference with two normal human gastric epithelial cells. Cell membrane localizations of potential targets on GSGC cell lines were determined by immunofluorescent (IF) staining. To correlate it with clinically-relevant GSGC tumor samples, immunohistochemical (IHC) staining of potential targets were performed in human diffuse GC tumor tissues along with normal gastric tissues. Next, GSGC cellular internalization capability of antibodies against potential targets was evaluated. Then, an optimized target was selected for developing GSGC-targeted ADCs. A series of ADC formulations with different linkers and payloads were constructed and characterized. Their anti-tumor activities against GSGC cell lines were subsequently screened in order to identify the optimized ADC formulation. Eventually, the anti-tumor activity and biosafety profile of the optimized ADC formulation were determined in suppressing tumor growth, progression and metastasis by using established orthotopic and peritoneal metastasis models of GSGC. Results: We first identified CD54 as a potential molecular target for human GSGCs using comparative flow cytometric analysis. We next evaluated its potential as an ADC target for GSGC-targeted therapy by determining its overexpression levels, cell membrane localizations, and cell internalization activity in GSGC cells. Furthermore, we constructed and characterized a panel of CD54-targeted ADCs and identified an optimized ADC formulation by quantitatively determining their half maximum inhibitory concentrations (IC50s) and validated its anti-tumor efficacy against GSGC tumors. Meanwhile, there was no evidence to indicate histopathological damages to normal organs in the optimized ADC treated group. Conclusions: In this study, we identified a molecular target for GSGC using an unbiased and quantitative screening assay and explored its potential application in developing GSGC-targeted ADCs. In order to maximize its efficacy, we optimized the ADC formulations against GSGC cells using different ADC linkers and payloads. Our study provides a promising targeted therapeutic candidate for the clinical treatment of GSGC. Citation Format: Rui Xu, Li Yuan, Xiao-Qing Guan, Shi-Li Yao, Bing Zhu, Tong Yang, Chun Liu, Peng Guo, Jiang-Jiang Qin, Xiang-Dong Cheng. Rationally developing antibody drug conjugates targeting genomically stable gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5293.

Background : Osteosarcoma (OS) is the most common malignant tumor of bone which was featured with osteoid or immature bone produced by the malignant cells, and biomarkers are urgently needed to identify patients with this aggressive disease. Methods : We downloaded gene expression profiles from Gene Expression Omnibus (GEO) and The Therapeutically Applicable Research to Generate Effective Treatments (TARGET) datasets for OS, respectively, and performed weighted gene co-expression network analysis (WGCNA) to identify the key module. Whereafter, functional annotation and Gene Set Enrichment Analysis (GSEA) demonstrated the relationships between target genes and OS. Results : In this study, we discovered four key genes – ALOX5AP, HLA-DMB, HLA-DRA and SPINT2 as new prognostic markers and confirmed their relationship with OS metastasis in the validation set. Conclusions : Overall, our work may shed light on the roles of ALOX5AP, HLA-DMB, HLA-DRA and SPINT2, thus providing valuable clues to investigate the metastasis of OS and corroborating the potential clinical application value of the 4-gene signature to some extent.

To better understand the genetic diversity, host association and evolution of coronaviruses (CoVs) in China we analyzed a total of 696 rodents encompassing 16 different species sampled from Zhejiang and Yunnan provinces. Based on the reverse transcriptase PCR-based CoV screening CoVs of fecal samples and subsequent sequence analysis of the RdRp gene, we identified CoVs in diverse rodent species, comprising Apodemus agrarius, Apodemus latronum, Bandicota indica, Eothenomys miletus, E. eleusis, Rattus andamanesis, Rattus norvegicus , and R. tanezumi. Apodemus chevrieri was a particularly rich host, harboring 25 rodent CoVs. Genetic and phylogenetic analysis revealed the presence of three groups of CoVs carried by a range of rodents that were closely related to the Lucheng Rn rat coronavirus (LRNV), China Rattus coronavirus HKU24 (ChRCoV_HKU24) and Longquan Rl rat coronavirus (LRLV) identified previously. One newly identified A. chevrieri -associated virus closely related to LRNV lacked an NS2 gene. This virus had a similar genetic organization to AcCoV-JC34, recently discovered in the same rodent species in Yunnan, suggesting that it represents a new viral subtype. Notably, additional variants of LRNV were identified that contained putative nonstructural NS2b genes located downstream of the NS2 gene that were likely derived from the host genome. Recombination events were also identified in the ORF1a gene of Lijiang-71. In sum, these data reveal the substantial genetic diversity and genomic complexity of rodent-borne CoVs, and greatly extend our knowledge of these major wildlife virus reservoirs.