A multicenter-retrospective cohort study of chromosome instability in lung cancer: clinical characteristics and prognosis of patients harboring chromosomal instability detected by metagenomic next-generation sequencing

Background: The usefulness of metagenomic next- generation sequencing (mNGS) in identifying the prognosis of lung cancer with chromosomal instability (CIN) remains unclear. We aimed to analyze clinical characteristics and prognosis of patients in patients harboring CIN. Methods: This retrospective cohort study included 668 patients diagnosed with suspected pulmonary infection or lung cancer whose samples underwent mNGS detection from January 2021 to January 2022. Difference between clinical characteristics were calculated by the Student's t-test and the chi-square test. The subjects were followed-up from registered to September 2022. Survival curves were analyzed by the Kaplan-Meier method. Results: Of 619 bronchoalveolar lavage fluid (BALF) samples collected by bronchoscopy, 30 CIN-positive samples were confirmed as malignant on histopathology, with a sensitivity of 61.22%, a specificity of 99.65%, and an 83.17% accuracy [ cut- off values were established by the receiver operating characteristic (ROC) area under the curve (AUC) =0.804]. In 42 patients with lung cancer, mNGS detected 24 patients as CIN-positive and 18 as CIN-negative. There were no differences between two groups including ages, pathologic types, stage and metastases. In 25 cases, we detected 523 chromosomal copy number variants (CNVs) with forms including duplication (dup), deletion (del), mosaic (mos), and whole chromosome amplification or loss. A total of 243 duplication variants and 192 deletion variants occurred in all chromosomes. Duplications occurred in most chromosomes except for Chr9 and Chr13, in which CNV tended to delete. The median overall survival (OS) in patients with Chr5p15 duplication was 32.4 months [95% confidence interval (CI), 10.35-54.45 months]. The median OS differed significantly between the 5p15dup+ group and the combined group (32.4 vs. 8.63 months, P=0.049). In 29 patients with unresected lung cancer, the median OS of 18 cases in the CIN-positive group was 32.4 months (95% CI, 14.2-50.6 months) and the median OS of 11 cases in the CIN-negative group was 35.63 months (95% CI, 21.64-49.62 months; Wilcoxon, P=0.227). Conclusions: Various forms of CIN detected by mNGS may predict prognosis of patients with lung cancer differentially. CIN with duplication or deletion deserves further study to guide clinical treatment.