scholarly journals Comprehensive Comparative Molecular Characterization of Young and Old Lung Cancer Patients

2022 ◽  
Vol 11 ◽  
Author(s):  
Mingming Hu ◽  
Jinjing Tan ◽  
Zhentian Liu ◽  
Lifeng Li ◽  
Hongmei Zhang ◽  
...  

BackgroundYoung lung cancer as a small subgroup of lung cancer has not been fully studied. Most of the previous studies focused on the clinicopathological features, but studies of molecular characteristics are still few and limited. Here, we explore the characteristics of prognosis and variation in young lung cancer patients with NSCLC.MethodsA total of 5639 young lung cancer samples (NSCLC, age ≤40) were screened from the SEER and the same number of the old (NSCLC, age ≥60) were screened by propensity score matching to evaluate the prognosis of two groups. 165 treatment-naïve patients diagnosed with NSCLC were enrolled to explore the molecular feature difference between two age-varying groups. CCLE cell line expression data was used to verify the finding from the cohort of 165 patients.ResultsThe overall survival of the young lung cancer group was significantly better than the old. Germline analysis showed a trend that the young group contained a higher incidence of germline alterations. The TMB of the young group was lower. Meanwhile, the heterogeneity and evolutionary degrees of the young lung cancer group were also lower than the old. The mutation spectrums of two groups exhibited variance with LRP1B, SMARCA4, STK11, FAT2, RBM10, FANCM mutations, EGFR L858R more recurrent in the old group and EML4-ALK fusions, BCL2L11 deletion polymorphism, EGFR 19DEL, 20IN more recurrent in the young group. For the base substitution, the young showed a lower fraction of transversion. Further, we performed a pathway analysis and found the EGFR tyrosine kinase inhibitor resistance pathway enriched in the young lung cancer group, which was validated in gene expression data later.ConclusionsThere were significantly different molecular features of the young lung cancer group. The young lung cancer group had a more simple alteration structure. Alteration spectrums and base substitution types varied between two groups, implying the different pathogenesis. The young lung cancer group had more potential treatment choices. Although young lung patients had better outcomes, there were still adverse factors of them, suggesting that the young group still needs more caution for treatment choice and monitoring after the treatment to further improve the prognosis.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 1527-1527
Author(s):  
Sebastian Yves Friedrich Michels ◽  
Matthias Scheffler ◽  
Masyar Gardizi ◽  
Marc Christiaan Allardt Bos ◽  
Lucia Nogova ◽  
...  

2021 ◽  
Author(s):  
Peiyi Xia ◽  
Lan Zhang ◽  
Pan Li ◽  
Enjie Liu ◽  
Wencai Li ◽  
...  

Abstract Background Complex kinase rearrangement, a mutational process involving one or two chromosomes with clustered rearrangement breakpoints, interferes with the accurate detection of kinase fusions by DNA-based next-generation sequencing (NGS). We investigated the characteristics of complex ALK rearrangements in non-small cell lung cancers using multiple molecular tests. Methods Samples of non-small cell lung cancer patients were analyzed by targeted-capture DNA-based NGS with probes tilling the selected intronic regions of fusion partner genes, RNA-based NGS, RT-PCR, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Results In a large cohort of 6576 non-small cell lung cancer patients, 343 (5.2%) cases harboring ALK rearrangements were identified. Fourteen cases with complex ALK rearrangements were identified by DNA-based NGS and classified into three types by integrating various genomic features, including intergenic (n = 3), intragenic (n = 5) and “bridge joint” rearrangements (n = 6). All thirteen cases with sufficient samples actually expressed canonical EML4-ALK fusion transcripts confirmed by RNA-based NGS. Besides, positive ALK IHC was detected in 13 of 13 cases, and 9 of 11 cases were positive in FISH testing. Patients with complex ALK rearrangements who received ALK inhibitors treatment (n = 6), showed no difference in progression-free survival (PFS) compared with patients with canonical ALK fusions(n = 36, P = 0.9291). Conclusions This study firstly reveals the molecular characteristics and clinical outcomes of complex ALK rearrangements in NSCLC, sensitive to ALK inhibitors treatment, and highlights the importance of utilizing probes tilling the selected intronic regions of fusion partner genes in DNA-based NGS for accurate fusion detection. RNA and protein level assay may be critical in validating the function of complex ALK rearrangements in clinical practice for optimal treatment decision.


2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Xuming Zhu ◽  
Huizhu Song ◽  
Yan Chen ◽  
Feifei Han ◽  
Qiong Wang ◽  
...  

Objective. Inflammation-driven markers play a crucial role in tumorigenesis and tumor progression. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in blood are systemic inflammatory response markers. Some reports have showed that NLR and PLR are related to a poor prognosis in patients with lung cancer. However, little studies have reported whether NLR and PLR can be diagnostic markers for lung cancer. The aim of the current study is to investigate the roles of NLR and PLR in diagnosing lung cancer. Methods. This study analyzed data from lung cancer patients and healthy individuals in Wuxi People’s Hospital Affiliated with Nanjing Medical University. The Mann–Whitney U test was performed to compare differences between the lung cancer group and the control group. Based on white blood cell (WBC) counts, both lung cancer patients and healthy individuals were divided into the low-level group, moderate-level group, and high-level group. The Kruskal-Wallis test was applied to compare differences of NLR and PLR among those groups with different WBC counts. Spearman correlation analysis was used to assess correlations. Receiver operating characteristic (ROC) curves were performed to determine diagnostic accuracy. Results. 210 patients diagnosed with lung cancer and 261 healthy subjects were enrolled in this study. Levels of NLR and PLR increased in the lung cancer group compared with the control group ( P < 0.001 ). For the lung cancer group, NLR levels could rise with the increasing of WBC levels ( P < 0.001 ) while PLR levels had no significant variation with the increasing of WBC levels ( P = 0.206 ). For the control group, NLR levels could rise with the increasing of WBC levels ( P < 0.001 ) while PLR levels would decline with the increasing of WBC levels ( P < 0.001 ). In the lung cancer group, both NLR and PLR had no significant correlations with aspartate transaminase, urea, and glucose. The area under the curve (AUC) with 95% confidence interval (95% CI) of NLR and PLR to distinguish lung cancer patients from healthy subjects was, respectively, 0.684 (0.634-0.735) and 0.623 (0.571-0.674). When NLR and PLR were combined, AUC (95% CI) increased to 0.691 (0.642-0.740). Conclusions. NLR and PLR alone have moderate ability to distinguish lung cancer patients from healthy subjects. Furthermore, combination forms of NLR and PLR can improve diagnostic ability.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17032-17032
Author(s):  
H. Guo ◽  
X. Hu ◽  
Z. Li

17032 Background: To explore the possibility that the standardized uptake value(SUV) of positron emission tomography(PET) could be a prognostic factor for lung cancer and whether it holds more significance than clinical stage,the current predominant prognostic factor for NSCLC patients. To assess the possible connection between the SUV and clinical and histopathologic characteristics of lung cancer patients(especially the histology), in order to build a comprehensive picture for the potential application of SUV. Methods: Eighty-two patients taking PET examination before receiving any treatment were analysed, the majority of which(fifty) consisted of patients treated with multiple modality treatment where surgery played a central role. 1-year and 3-year survival(OS) Rate, Progress Free Survival(PFS) Rate were calculated by Kaplan-Meier method and evaluated with the log-rank test.The prognostic significance was assessed by univariate and multivariate analyses.Nonparametric tests were performed to determine whether there was valuable difference amid each SUV group classified by certain clinical or histopathologic characteristic. Results: A SUV cutoff of 5.0 for the primary tumor showed the greatest discriminative value for overall survival.As for the PFS,the cufoff is 4.0. The SUV for the primary tumor was a significant predictor for both overall survival and PFS, based on the result that the relative risk was 7.075 and 2.719 respectively. As a result of multivariate analyse,the prognostic value of SUV and Clinical Staging was independent of each other, and the value of the SUV was considerably higher than the latter. The SUV for the small-cell lung cancer group was statistically higher than the non-small-cell lung cancer group. And there was significant overall discrepancy across the groups sorted by the degree of differentiation. Conclusions: The SUV of the primary tumor has the potential to be the leading prognostic factor for patients treated by multiple modality treatment, leading to substantially improved management for lung cancer patients. And there could be close connection between SUV and histopathologic or differentiation feature of lung cancer tissue, although it is still open to discussion. Analysis for larger number of cases could settle the issue. No significant financial relationships to disclose.


Sign in / Sign up

Export Citation Format

Share Document