Background: Secreted phosphoprotein 1 (SPP1) plays a vital role in tumor progression of multiple cancer types However, it still awaits further exploration whether SPP1 is a bystander or an actual player in the modulation of immune infiltration in ovarian cancer. Methods: In this study, the expression level of SPP1 was identified by Oncomine, GEPIA and TIMER databases, and the result of SPP1 immumohistochemical staining was acquired by The HPA database. The impact of SPP1 expression level on the clinical outcome of ovarian cancer patients were evaluated via Kaplan–Meier Plotter and PrognoScan dataset. Immune infiltration analyses were conducted using TIMER and TISIDB dataset. In addition, Functional enrichment analyses were performed with Metascape and GeneMANIA database. To verify these findings from the public database, the results were validated in a cohort of ovarian cancer patients. Results: SPP1 was found to be overexpressed in ovarian tumor tissues and high SPP1 expression was correlated with shorter survivals. Notably, SPP1 expression was positively correlated with infiltrating levels of CD4 + T cells, CD8 + T cells, macrophages, neutrophils, and dendritic cells. Furthermore, SPP1 expression level showed strong correlation with diverse immune cells in ovarian cancer. Of note, functional enrichment analysis suggested that SPP1 was strongly correlated with immune response. Conclusions: These findings imply that SPP1 is correlated with prognosis and immune cell infiltrating, offering a new potential immunotherapeutic target in ovarian cancer. Trial registration: Not applicable.

Jiang R, et al. J Gynecol Oncol. 2019 Jun;31:e86. https://doi.org/10.3802/jgo.2020.31.e86

Ovarian cancer is one of the most common cancers in women and is often diagnosed as advanced stage because of the subtle symptoms of early ovarian cancer. To identify the somatic alterations and new biomarkers for the diagnosis and targeted therapy of Chinese ovarian cancer patients, a total of 65 Chinese ovarian cancer patients were enrolled for detection of genomic alterations. The most commonly mutated genes in ovarian cancers were TP53 (86.15%, 56/65), NF1 (13.85%, 9/65), NOTCH3 (10.77%, 7/65), and TERT (10.77%, 7/65). Statistical analysis showed that TP53 and LRP1B mutations were associated with the age of patients, KRAS, TP53, and PTEN mutations were significantly associated with tumor differentiation, and MED12, LRP2, PIK3R2, CCNE1, and LRP1B mutations were significantly associated with high tumor mutational burden. The mutation frequencies of LRP2 and NTRK3 in metastatic ovarian cancers were higher than those in primary tumors, but the difference was not significant (P = 0.072, for both). Molecular characteristics of three patients responding to olapanib supported that BRCA mutation and HRD related mutations is the target of olaparib in platinum sensitive patients. In conclusion we identified the somatic alterations and suggested a group of potential biomarkers for Chinese ovarian cancer patients. Our study provided a basis for further exploration of diagnosis and molecular targeted therapy for Chinese ovarian cancer patients.

Biomarkers identified for prostate cancer patients through genome-scale screening Biomarkers identified for prostate cancer patients through genome-scale screening

Tumor-associated neutrophils (TANs) actively interact with antibody-drug conjugates (ADCs) within the tumor microenvironment (TME), though the detailed mechanisms governing their response to ADC treatment remain to be fully elucidated. Herein, we explored how ICAM1-targeted ADCs affect TAN dynamics in preclinical models of cervical cancer. We discovered that I-DXd, our in-house ADC targeting cervical cancer, effectively eliminates tumor cells through specific antigen recognition while concurrently depleting pro-tumor VEGFA + TANs via Fcγ receptor-mediated phagocytosis. This dual action promotes an immunologically favorable TME. Through comprehensive preclinical studies, we established a foundational understanding of the synergistic benefits of combining I-DXd treatment with PD-1 immune checkpoint inhibition, thereby opening new avenues for therapeutic intervention in advanced cervical cancer.

In this work, maleimide-containing polymer inverse opals have been successfully prepared by utilization of an acrylate monomer bearing a masked (protected) maleimide unit. As an ideal clickable functional group, maleimide can promote the Michael addition of thiol-containing molecules and the thermoreversible Diels–Alder reaction of furan derivatives, providing tremendous opportunities to produce various functional materials from one maleimide-containing polymer. As a demonstration, four chemical systems were facilely evolved from the prepared maleimide-containing inverse opal. By exploiting the nucleophilic thiol–ene reaction of maleimide, the zwitterionic pH-responsive inverse opal and electroactive inverse opal were first fabricated by reacting with cysteine and thiol-containing ferrocene derivatives, respectively. Based on the same reaction, it was also found that the maleimide-containing inverse opal could serve as a self-reporting sensing platform to sensitively detect the reduction of oxidized glutathione by specific enzymes. On the other hand, the thermoreversible nature of the Diels–Alder reaction of the maleimide groups made it possible to construct a dynamic molecule gating system by reacting with alkyl-chain-substituted furan derivatives from the prepared interconnected macroporous film. In fact, due to the unlimited variety provided by the two kinds of reactions mentioned above, the described photonic material exhibits a significant extendibility and could be easily post-modified for special purposes with maintenance of the opaline structure. Thus, this novel clickable maleimide-containing polymer inverse opal could serve as a reactive platform for producing a variety of functional photonic materials.