Abstract 6186: Protein panel for predicting the efficacy of neoadjuvant therapy for rectal cancer based on proteomics

Abstract

Abstract Background: Colorectal cancer (CRC) is the second leading cause of cancer death worldwide and more than 1/3 of all cases are rectal cancer.With the development of early diagnosis and precise treatment, the 5-year survival rate of rectal cancer has been greatly improved. Neoadjuvant radiotherapy and chemotherapy, as the standard treatment for locally advanced rectal cancer, have been included in the NCCN guidelines. However, due to tumor heterogeneity,the response rate to neoadjuvant radiotherapy and chemotherapy varies, and there is no effective method to predict the efficacy of neoadjuvant therapy for rectal cancer. The recent advance of pressure cycling technology (PCT) and data-independent acquisition mass spectrometry (DIA-MS) allows high-throughput and reproducible proteomic quantification for formalin-fixed paraffin-embedded (FFPE) biopsy-level tissue proteome. Methods: We collected 33 patients with rectal cancer who were treated with long-term radiotherapy and capecitabine chemotherapy in our center as the training cohort. Among them, a total of 23 cases with both pre-treatment endoscopic biopsy specimens and surgical pathological sections available were procured and reassessed the Tumor Regression Grade (TRG) after treatment as mentioned above. FFPE tissue samples from each individual were collected with two biological replicates. We further collected other 31 patients from another two independent hospitals as the validation cohort. All the samples were processed by PCT-DIA for proteomic profiling. Candidate proteins were selected from training cohort and confirmed in the validation cohort, as well as Immunohistochemistry (IHC). Results: A total of 5055 SwissProt proteins are quantified with high confidence and a high degree of reproducibility (R2=0.983) from 46 samples in the training cohort. Patients in training cohort were divided into two groups according to responsiveness to radiotherapy (TRG1+2: no significant benefit from radiotherapy; TRG3+4: significant benefit from radiotherapy) to explore differentially expressed proteins (adjusted p value < 0.05, fold change > 2). 35 up-regulated proteins and 114 down-regulated proteins were detected in the responded group. The suppressed proteins were mainly involved in immune response and cell activation, while the elevated proteins mostly participate metabolic processes. Six differentially expressed proteins were further confirmed in the validation cohort using DIA-MS and IHC. More details will be presented. Conclusion: We developed a predictive model composed of 6 proteins which exhibited promising roles for the responsiveness to neoadjuvant therapy in rectal patients. Citation Format: Kailun Xu, Biting Zhou, Xi Zheng, Yingkuan Shao, Jian Wang, Tiannan Guo, Shu Zheng. Protein panel for predicting the efficacy of neoadjuvant therapy for rectal cancer based on proteomics [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 6186.