Predictive value of proteomic markers for advanced rectal cancer with neoadjuvant chemoradiotherapy

Abstract

Background Preoperative neoadjuvant chemoradiation (nCRT) has been the standard treatment for locally advanced rectal cancer. Serum biomarkers to stratify patients with respect to prognosis and response to nCRT are needed due to the diverse response to the therapy. Methods Thirteen paired pre- and post-nCRT sera from rectal cancer patients were analyzed by isobaric tags for relative and absolute quantitation (iTRAQ) method. Twenty-five proteins were selected for validation by parallel reaction monitoring (PRM) in ninety-one patients. Results Totally, 310 proteins were identified and quantified in sera samples. Reactome pathway analysis showed that the immune activation-related pathways were enriched in response to nCRT. Twenty-five proteins were selected for further validation. PRM result showed that the level of PZP was higher in pathological complete response (pCR) patients than non-pCR patients. The Random Forest algorithm identified a prediction model composed of 10 protein markers, which allowed discrimination between pCR patients and non-pCR patients (area under the curve (AUC) = 0.886 on testing set). Higher HEP2 and GELS or lower S10A8 in baseline sera were associated with better prognosis. Higher APOA1 in post nCRT sera was associated with better disease-free survival (DFS). Conclusions We identified and confirmed a 10-protein panel for nCRT response prediction and four potential biomarkers HEP2, GELS, S10A8 and APOA1 for prognosis of rectal cancer based on iTRAQ-based comparative proteomics screening and PRM-based targeted proteomic validation.

High-Level Secretion of Pregnancy Zone Protein Is a Novel Biomarker of DNA Damage-Induced Senescence and Promotes Spontaneous Senescence

“…Third, a large number of transcriptional profilings performed in cells at senescence demonstrated that transcription alterations are the hallmark of cellular senescence. , In our study, we found that transcription of the PZP gene is upregulated at senescence or following DNA damage, strengthening the important role of transcription reprogramming in the induction of cellular senescence. In support of our finding, a recent study showed that elevated serum PZP was detected in colorectal cancer patients sensitive to a neo-adjuvant chemo-radiotherapy, but not detected in patients insensitive to the neo-adjuvant chemo-radiotherapy . This observation hints that the elevated serum PZP might have originated from the DNA damage-responsive cancer cells or DNA damage-induced senescent cancer cells.…”

“…In support of our finding, a recent study showed that elevated serum PZP was detected in colorectal cancer patients sensitive to a neo-adjuvant chemo-radiotherapy, but not detected in patients insensitive to the neo-adjuvant chemoradiotherapy. 42 This observation hints that the elevated serum PZP might have originated from the DNA damage-responsive cancer cells or DNA damage-induced senescent cancer cells. Most strikingly, we found that PZP gene transcription is independent of p53 signaling, indicating that the key transcription factor responsible for the activation of the PZP gene remains to be answered in the future.…”

Multi-omics staging of locally advanced rectal cancer predicts treatment response: a pilot study

“…Tumor growth follows a variety of metabolic pathways resulting in the accumulation of specific intermediate metabolites and metabolomics represent a growing discipline in the characterization of serum metabolites in cancer [ 19 , 20 ] can be used as prognostic markers for response to CRT. [ 21 – 25 ]. To date, integrating “-omics” disciplines may represent a new framework for personalized cancer care.…”

Expression levels and diagnostic value of serum GDNF, CEA and CA199 in patients with colorectal carcinoma

“…However, single detection of CEA or CA199 has a low positive rate and insufficient sensitivity and cannot obtain positive results [4] , and their combined detection is needed. Glial cell line-derived neurotrophic factor (GDNF) is a substance secreted by enteric glial cells to promote the growth and differentiation of enteric neurons and maintain the homeostasis of the intestinal environment [5] . It can bind to the glial cell-derived neurotrophic factor receptor-α (GFRα) and RET receptor tyrosine kinase respectively to form the GDNF-GFRa-RET signaling pathway, which subsequently affects the occurrence and development of tumors [6] .…”