He Wang

Resistance prediction in high‐grade serous ovarian carcinoma with neoadjuvant chemotherapy using data‐independent acquisition proteomics and an ovary‐specific spectral library

High‐grade serous ovarian carcinoma (HGSOC) is the most common subtype of ovarian cancer with 5‐year survival rates below 40%. Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is recommended for patients with advanced‐stage HGSOC unsuitable for primary debulking surgery (PDS). However, about 40% of patients receiving this treatment exhibited chemoresistance of uncertain molecular mechanisms and predictability. Here, we built a high‐quality ovary‐specific spectral library containing 130 735 peptides and 10 696 proteins on Orbitrap instruments. Compared to a published DIA pan‐human spectral library (DPHL), this spectral library provides 10% more ovary‐specific and 3% more ovary‐enriched proteins. This library was then applied to analyze data‐independent acquisition (DIA) data of tissue samples from an HGSOC cohort treated with NACT, leading to 10 070 quantified proteins, which is 9.73% more than that with DPHL. We further established a six‐protein classifier by parallel reaction monitoring (PRM) to effectively predict the resistance to additional chemotherapy after IDS (Log‐rank test, P  = 0.002). The classifier was validated with 57 patients from an independent clinical center ( P  = 0.014). Thus, we have developed an ovary‐specific spectral library for targeted proteome analysis, and propose a six‐protein classifier that could potentially predict chemoresistance in HGSOC patients after NACT‐IDS treatment.

Establishment of multifactor predictive models for the occurrence and progression of cervical intraepithelial neoplasia

Abstract Background To study the risk factors involved in the occurrence and progression of cervical intraepithelial neoplasia (CIN) and to establish predictive models. Methods Genemania was used to build a gene network. Then, the core gene-related pathways associated with the occurrence and progression of CIN were screened in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) experiments were performed to verify the differential expression of the identified genes in different tissues. R language was used for predictive model establishment. Results A total of 10 genes were investigated in this study. A total of 30 cases of cervical squamous cell cancer (SCC), 52 cases of CIN and 38 cases of normal cervix were enrolled. Compared to CIN cases, the age of patients in the SCC group was older, the number of parities was greater, and the percentage of patients diagnosed with CINII+ by TCT was higher. The expression of TGFBR2, CSKN1A1, PRKCI and CTBP2 was significantly higher in the SCC groups. Compared to patients with normal cervix tissue, the percentage of patients who were HPV positive and were diagnosed with CINII+ by TCT was significantly higher. FOXO1 expression was significantly higher in CIN tissue, but TGFBR2 and CTBP2 expression was significantly lower in CIN tissue. The significantly different genes and clinical factors were included in the models. Conclusions Combination of clinical and significant genes to establish the random forest models can provide references to predict the occurrence and progression of CIN.