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Objective: To investigate the predictive value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for the efficacy and prognosis of programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors in driver-gene-negative advanced non-small-cell lung cancer (NSCLC). Methods: A retrospective analysis of 107 advanced NSCLC patients without gene mutations who received PD-1/PD-L1 inhibitors in our hospital from January 2020 to June 2022 was performed. NLR and PLR were collected before PD-1/PD-L1 inhibitors, the optimal cut-off values of NLR and PLR were determined according to the receiver operating characteristic (ROC) curve, and the effects of NLR and PLR on the efficacy of PD-1/PD-L1 inhibitors in advanced NSCLC patients were analyzed. Results: A total of 107 patients were included in this study. Receiver operating characteristic analysis showed that the optimal cut-off values of NLR and PLR were 3.825, 179, respectively. Kaplan–Meier curve showed that low baseline levels NLR and PLR were associated with an improvement in both progression-free survival (PFS) (P <.001, <.001, respectively) and overall survival (OS) (P =.009,.006, respectively). In first-line treatment and non-first-line treatment, low baseline levels NLR and PLR were associated with an improvement in PFS. In multivariate analysis, low baseline NLR and PLR showed a strong association with both better PFS (P =.011,.027, respectively) and longer OS (P =.042,.039, respectively). Conclusion: Low baseline NLR and PLR levels are significantly associated with better response in advanced NSCLC patients treated with PD-1/PD-L1 inhibitors, which may be indicators to predict the efficacy of immunotherapy in advanced NSCLC with driver-gene-negative. [ABSTRACT FROM AUTHOR]

The improvement of treatment for patients with ‘driver‐gene‐negative’ lung adenocarcinoma (LUAD) remains a critical problem to be solved. We aimed to explore the role of methylation of N6 adenosine (m6A)‐related long noncoding RNA (lncRNA) in stratifying ‘driver‐gene‐negative’ LUAD risk. Patients negative for mutations in EGFR, KRAS, BRAF, HER2, MET, ALK, RET, and ROS1 were identified as ‘driver‐gene‐negative’ cases. RNA sequencing was performed in 46 paired tumors and adjacent normal tissues from patients with ‘driver‐gene‐negative’ LUAD. Twenty‐three m6A regulators and relevant lncRNAs were identified using Pearson's correlation analysis. K‐means cluster analysis was used to stratify patients, and a prognostic nomogram was developed. The CIBERSORT and pRRophetic algorithms were employed to quantify the immune microenvironment and chemosensitivity. We identified two clusters highly consistent with the prognosis based on their unique expression profiles for 46 m6AlncRNAs. A risk model constructed from nine m6A lncRNAs could stratify patients into high‐ and low‐risk groups with promising predictive power (C‐index = 0.824), and the risk score was an independent prognostic factor. The clusters and risk models were closely related to immune characteristics and chemosensitivity. Additional pan‐cancer analysis using the nine m6AlncRNAs showed that the expression of DIO3 opposite strand upstream RNA (DIO3OS) is closely related to the immune/stromal score and tumor stemness in a variety of cancers. Our results show that m6AlncRNAs are a reliable prognostic tool and can aid treatment decision‐making in ‘driver‐gene‐negative’ LUAD. DIO3OS is associated with the development of various cancers and has potential clinical applications.

The improvement of treatment for patients with 'driver‐gene‐negative' lung adenocarcinoma (LUAD) remains a critical problem to be solved. We aimed to explore the role of methylation of N6 adenosine (m6A)‐related long noncoding RNA (lncRNA) in stratifying 'driver‐gene‐negative' LUAD risk. Patients negative for mutations in EGFR, KRAS, BRAF, HER2, MET, ALK, RET, and ROS1 were identified as 'driver‐gene‐negative' cases. RNA sequencing was performed in 46 paired tumors and adjacent normal tissues from patients with 'driver‐gene‐negative' LUAD. Twenty‐three m6A regulators and relevant lncRNAs were identified using Pearson's correlation analysis. K‐means cluster analysis was used to stratify patients, and a prognostic nomogram was developed. The CIBERSORT and pRRophetic algorithms were employed to quantify the immune microenvironment and chemosensitivity. We identified two clusters highly consistent with the prognosis based on their unique expression profiles for 46 m6AlncRNAs. A risk model constructed from nine m6A lncRNAs could stratify patients into high‐ and low‐risk groups with promising predictive power (C‐index = 0.824), and the risk score was an independent prognostic factor. The clusters and risk models were closely related to immune characteristics and chemosensitivity. Additional pan‐cancer analysis using the nine m6AlncRNAs showed that the expression of DIO3 opposite strand upstream RNA (DIO3OS) is closely related to the immune/stromal score and tumor stemness in a variety of cancers. Our results show that m6AlncRNAs are a reliable prognostic tool and can aid treatment decision‐making in 'driver‐gene‐negative' LUAD. DIO3OS is associated with the development of various cancers and has potential clinical applications. [ABSTRACT FROM AUTHOR]

ObjectiveProgrammed cell death 1 (PD-1) inhibitor has been in the market in China for several years, which lacks sufficient domestic evidence regarding its application in lung cancer. Thus, this study intended to assess the treatment outcome and tolerance of PD-1 inhibitor plus chemotherapy in advanced, driver-gene-negative, nonsquamous, non-small-cell lung cancer (NSCLC) patients in a real clinical setting.MethodsThis retrospective cohort study analyzed 68 advanced driver-gene-negative nonsquamous NSCLC patients, among which 38 cases received PD-1 inhibitor plus chemotherapy and 30 cases adopted chemotherapy alone. Disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events were reviewed.ResultsGenerally, PD-1 inhibitor plus chemotherapy achieved a more satisfying ORR compared with chemotherapy alone (52.6% vs. 30.0%, P = 0.061), while the DCR did not vary between PD-1 inhibitor plus chemotherapy and chemotherapy (84.2% vs. 73.3%, P = 0.271). Patients receiving PD-1 inhibitor plus chemotherapy exhibited favorable PFS (median: 10.1 vs. 7.1 months, P = 0.040) and OS (median: 17.4 vs. 13.9 months, P = 0.049) than patients adopting chemotherapy alone. Additionally, after adjustment using multivariable Cox's analyses, PD-1 inhibitor plus chemotherapy (vs. chemotherapy) could independently realize prolonged PFS (P = 0.020) and OS (P = 0.029). Moreover, the majority of adverse events were manageable; meanwhile, grade 3–4 adverse events included leukopenia (13.2%), neutropenia (13.2%), nausea and vomiting (7.9%), anemia (5.3%), elevated transaminase (5.3%), thrombopenia (2.6%), anorexia (2.6%), peripheral neuropathy (2.6%), and rash (2.6%).ConclusionPD-1 inhibitor plus chemotherapy exhibits a better efficacy and equal tolerance compared with chemotherapy alone in advanced driver-gene-negative nonsquamous NSCLC patients.

Objective: Programmed cell death 1 (PD-1) inhibitor has been in the market in China for several years, which lacks sufficient domestic evidence regarding its application in lung cancer. Thus, this study intended to assess the treatment outcome and tolerance of PD-1 inhibitor plus chemotherapy in advanced, driver-gene-negative, nonsquamous, non-small-cell lung cancer (NSCLC) patients in a real clinical setting., Methods: This retrospective cohort study analyzed 68 advanced driver-gene-negative nonsquamous NSCLC patients, among which 38 cases received PD-1 inhibitor plus chemotherapy and 30 cases adopted chemotherapy alone. Disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events were reviewed., Results: Generally, PD-1 inhibitor plus chemotherapy achieved a more satisfying ORR compared with chemotherapy alone (52.6% vs. 30.0%, P  = 0.061), while the DCR did not vary between PD-1 inhibitor plus chemotherapy and chemotherapy (84.2% vs. 73.3%, P  = 0.271). Patients receiving PD-1 inhibitor plus chemotherapy exhibited favorable PFS (median: 10.1 vs. 7.1 months, P  = 0.040) and OS (median: 17.4 vs. 13.9 months, P  = 0.049) than patients adopting chemotherapy alone. Additionally, after adjustment using multivariable Cox's analyses, PD-1 inhibitor plus chemotherapy (vs. chemotherapy) could independently realize prolonged PFS ( P  = 0.020) and OS ( P  = 0.029). Moreover, the majority of adverse events were manageable; meanwhile, grade 3-4 adverse events included leukopenia (13.2%), neutropenia (13.2%), nausea and vomiting (7.9%), anemia (5.3%), elevated transaminase (5.3%), thrombopenia (2.6%), anorexia (2.6%), peripheral neuropathy (2.6%), and rash (2.6%)., Conclusion: PD-1 inhibitor plus chemotherapy exhibits a better efficacy and equal tolerance compared with chemotherapy alone in advanced driver-gene-negative nonsquamous NSCLC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Li, Yang, Zhou, Yang and Wu.)