The average copy number variation (CNVA) of chromosome fragments is a potential surrogate marker for TMB in predicting responses to immunotherapy in Non-small cell lung cancer

Yuan yuan LeiJie He


Background: Genomic instability plays a large role in the process of cancer. Tumor mutational burden (TMB) is closely related to immunotherapy outcome and is an important manifestation of genomic instability. However, the cost of TMB detection is extremely high, which limits the use of TMB in clinical practice. Another new indicator of genome instability, CNVA (the average copy number variation) which calculates the changes of 0.5 Mb chromosomal fragments, requires extremely low sequencing depth, and is expected to replace TMB as a new marker of immune efficacy.Methods: A total of 50 samples (23 of which came from patients who received immunotherapy) were subjected to low-depth (10X) chromosome sequencing on the MGI platform. CNVA was calculated by the formula avg (abs (copy number-2)). Then, we analyzed the relationship between CNVA and immune infiltration or immunotherapy efficacy. In addition, through the analysis of whole genome sequencing data of 509 lung adenocarcinoma in the TCGA database, we compared CNVA with classic marker TMB to evaluate the value of CNVA as an immune evaluation index.Results: Compared with the low CNVA group, the high CNVA group had higher expression of PD-L1, CD39 and CD19, and more infiltration of...Continue Reading

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