Single-cell transcriptomics reveal DHX9 in mature B cell as a dynamic network biomarker before lymph node metastasis in CRC

Abstract

Increasing evidence indicates that mature B cells in the adjacent tumor tissue, both as an intermediate state, are vital in advanced colorectal cancer (CRC), which is associated with a low survival rate. Developing predictive biomarkers that detect the tipping point of mature B cells before lymph node metastasis in CRC is critical to prevent irreversible deterioration. We analyzed B cells in the adjacent tissues of CRC samples from different stages using the dynamic network biomarker (DNB) method. Single-cell profiling of 725 CRC-derived B cells revealed the emergence of a mature B cell subtype. Using the DNB method, we identified stage II as a critical period before lymph node metastasis and that reversed difference genes triggered by DNBs were enriched in the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway involving B cell immune capability. DHX9 (DEAH-box helicase 9) was a specific para-cancerous tissue DNB key gene. The dynamic expression levels of DHX9 and its proximate network genes involved in B cell-related pathways were reversed at the network level from stage I to III. In summary, DHX9 in mature B cells of CRC-adjacent tissues may serve as a predictable biomarker and a potential immune target in CRC progression.

The enigmatic helicase DHX9 as a candidate prognostic biomarker for resected pancreatic ductal adenocarcinoma

“…Additionally, Liu et al. ( 20 ) found that DHX9 in mature B cell may be a dynamic network biomarker before lymph node metastasis in CRC, which may be consistent with our findings that DHX9 expression was remarkably associated with lymph node metastasis.…”

“…The same results were obtained in HCC that the high DHX9 expression was obviously correlated with metastasis, vascular invasion, and TNM stage and was verified as an independent adverse prognostic indicator (19). Additionally, Liu et al (20) found that DHX9 in mature B cell may be a dynamic network biomarker before lymph node metastasis in CRC, which may be consistent with our findings that DHX9 expression was remarkably associated with lymph node metastasis.…”

MAPKAPK2, a dynamic network biomarker of α-synuclein before its aggregation, was significantly highly expressed in both the brain and peripheral blood of PD patients

“…We used Cytoscape software (version 3.7.1) to export the adjacency matrix for visualization and applied the CytoHubba plugin to perform a topological analysis, in which the node genes were ranked on the basis of their properties in the network, and then, the 100 genes with the highest rankings were visualized. 27 Transcription factor annotation AnimalTFDB (v3.0) is a database of 125,135 TFs and 80,060 transcription cofactors that are classi ed and annotated at the genome-wide level for 97 species, with various functions, such as transcription, and prediction of transcription factor-binding sites. In this study, we used human the TF database (HumanTFDB), an independent web interface, to annotate DNB genes to facilitate the analysis of the network regulatory relationships involving DNB genes.…”

“…The DNB method has been used in studies in several elds for research into, for example, colorectal cancer metastasis, the epithelial-mesenchymal transformation and breast cancer. 21,22,23 Compared to traditional molecular biomarkers that are used to detect disease states on the basis of their differential molecular levels measured at a single time point, the DNB method integrates temporal information, and this case was chosen for its superiority in identifying the critical time before prepathological aggregation of the α-Syn state (the tipping point just before the dramatic transition from the physiological tetramer state to the pathological state of α-Syn aggregation). The DNB method revealed the key genes with changed expression before pathological aggregation of α-Syn and biomarkers useful for early diagnosis of diseases associated with the pathological aggregation of α-Syn, contributing to the study of the mechanisms underlying the pathological aggregation of α-Syn.…”

Low expression of the dynamic network markers FOS/JUN in pre-deteriorated epithelial cells is associated with the progression of colorectal adenoma to carcinoma

“…The main causes of T cell exhaustion were found to be the hub genes CCT6A and TUBA1B [ 15 ]. According to single-cell analysis of CRC adjacent tissue B cells, stage II was a crucial stage before lymph node metastasis, and the DHX9 gene participated in dynamic network changes during CRC development [ 16 ]. In addition, several research teams have applied the DNB method to examine lung metastasis in hepatocellular carcinoma, as well as irreversible alterations during cell differentiation [ 17 , 18 ].…”