Yang Chengliang,Peng Liangqun,Luo Hui,et al.Proteomic screening of plasma biomarkers to identify predictive factors for predicting the efficacy of neoadjuvant chemoradiotherapy in rectal cancer[J].Chinese Journal of Radiological Medicine and Protection,2026,46(1):43-49
Proteomic screening of plasma biomarkers to identify predictive factors for predicting the efficacy of neoadjuvant chemoradiotherapy in rectal cancer
Received:December 10, 2024  
DOI:10.3760/cma.j.cn112271-20241210-00471
KeyWords:Rectal cancer  Neoadjuvant chemoradiotherapy  Proteomics  Treatment response  Biomarker
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Author NameAffiliationE-mail
Yang Chengliang Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University/HNHC Key laboratory of Radiation Oncology, Zhengzhou 450008, China dcluohui@163.com 
Peng Liangqun Department of General Surgery, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China  
Luo Hui Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University/HNHC Key laboratory of Radiation Oncology, Zhengzhou 450008, China  
Nie Wenna China-US(Henan) Hormel Cancer Institute, Zhengzhou 450003, China  
Liu Hui Basic Medical College of Zhengzhou University, Zhengzhou 450001, China  
Zhang Yanping Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University/HNHC Key laboratory of Radiation Oncology, Zhengzhou 450008, China  
Xu Meng Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University/HNHC Key laboratory of Radiation Oncology, Zhengzhou 450008, China  
Wang Yiwu Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University/HNHC Key laboratory of Radiation Oncology, Zhengzhou 450008, China  
Wu Mingxia Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University/HNHC Key laboratory of Radiation Oncology, Zhengzhou 450008, China  
Ge Hong Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University/HNHC Key laboratory of Radiation Oncology, Zhengzhou 450008, China  
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Abstract::
      Objective To identify serum-based biomarkers predicting early response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) with proteomics. Methods This study retrospectively analyzed and included 112 patients with newly diagnosed LARC who treated with nCRT in the Affiliated Cancer Hospital of Zhengzhou University from January 2018 to December 2023. Serum was collected prior to treatment and 1 week after nCRT. nCRT treatment response was evaluated post-surgery for all the tumor tissue samples according to tumor regression grade (TRG). The serum samples of patient achieved TRG0 were analyzed using an isobaric tag for relative and absolute quantification-based (iTRAQ) proteomics platform. Differentially expressed proteins were identified by bioinformatics analysis. The key differentially expressed proteins were verified using clinical plasma samples with enzyme-linked immunosorbent assay (ELISA) and animal experiments. Results A total of 19 patients achieved TRG0, who had 439 proteins screened by serum proteomics. Among them, 67 proteins were significantly up-regulated and 31 proteins were significantly down-regulated before and 1 week after nCRT. Enrichment analysis showed that the proteins of complement cascades significantly up-regulated (t = 2.17-4.93, P<0.05). ELISA analysis confirmed the level of complement in patients with TRG grade 0 and 1 was significantly higher than that in patients with TRG grade 2 and 3 (t = 4.55-9.01, P<0.05). Animal experiments showed that inhibition of complement reduced the efficacy of radiotherapy (t = 3.07, P<0.05). Conclusions Complement cascades associated proteins can be used to predict the efficacy of radiotherapy at early phase during the course of nCRT in LARC patients, serum complement C3 can serve as a potential reference indicator for antitumor treatment.
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