Background: Depression represents a significant clinical concern for individuals diagnosed with non-small cell lung cancer (NSCLC) following surgical resection. This study aimed to investigate the potential of preoperative peripheral blood parameters, including the neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), and platelet/lymphocyte ratio (PLR), as predictive indicators for the risk of developing depression within the initial 90-day postoperative period in NSCLC patients.

Methods: A prospective cohort study was conducted, enrolling 350 NSCLC patients, with 250 participants in the training set and 100 participants in the testing set. Participants were classified based on the presence or absence of depression 90 days after surgery. Preoperative blood parameters, including NLR, LMR, PLR, and inflammatory biomarkers, were measured. Statistical analyses, encompassing Logistics regression analysis and receiver operating characteristic (ROC) curve analysis, were performed to assess the significance and predictive value of these blood parameters. Multivariate predictive models were constructed based on the identified significant parameters.

Results: In the training set, statistically significant differences were observed between the non-depression and depression groups for NLR (4.35 ± 1.23 vs. 3.14 ± 0.82, t = 8.715, p < 0.001), LMR (3.84 ± 1.58 vs. 5.58 ± 1.23, t = 8.849, p < 0.001), PLR (187.46 ± 35.26 vs. 152.36 ± 32.46, t = 7.112, p < 0.001), and various blood parameters. Logistics regression analysis showed significant associations between NLR, LMR, PLR, and postoperative depression. ROC curve analysis indicated the predictive value of NLR [area under the curve (AUC) = 0.794], LMR (AUC = 0.800), and PLR (AUC = 0.766), with the multivariate model yielding an AUC of 0.931. These results were consistent in the testing set, where significant differences were observed between the non-depression and depression groups for NLR (4.23 ± 1.24 vs. 3.13 ± 0.75, t = 5.417, p < 0.001), LMR (3.17 ± 1.55 vs. 4.76 ± 1.22, t = 5.412, p < 0.001), PLR (189.46 ± 46.58 vs. 151.48 ± 34.26, t = 4.481, p < 0.001), and various blood parameters. The AUC values were 0.771, 0.791, and 0.755 for NLR, LMR, and PLR, respectively, while the multivariate model yielded an AUC of 0.928.

Conclusions: The study highlights the potential of preoperative peripheral blood NLR, LMR, and PLR as predictive indicators for the risk of postoperative 90-day depression in patients with NSCLC.

Clinical Trial Registration: Approval number: ChiCTR2300070375, https://www.chictr.org.cn/index.html.