Re-evaluating the need for mediastinal lymph node dissection and exploring lncRNAs as biomarkers of N2 metastasis in T1 lung adenocarcinoma

Abstract

Background: Although a well-acknowledged component of curative surgery for lung cancer, investigators have recently questioned the need for mediastinal lymph node dissection (MLND) in early-stage lung cancer cases. As such, the accurate prediction of N2 stage prior to surgery has become increasingly critical. But diagnostic biomarkers predicting N2 metastases are deficient, which are urgently needed.Methods: We extracted the data of non-small cell lung cancer (NSCLC) patients whose clinical information and follow-up data are complete and without preoperative induction therapy from the Surveillance, Epidemiology, and End Results (SEER) database. The SEER program registries routinely collect demographic and clinic data on patients. And the prognostic differences were analyzed according to the presence or absence of MLND in their lung resection using the R package. Subsequently, the correlations between pN2 metastasis and clinical characteristics were analyzed. In parallel, the long noncoding RNAs (lncRNAs) associated with pN2 status were screened in The Cancer Genome Atlas (TCGA) database by expression difference analysis between pN0-N1 and pN2 patients using limma. Their diagnostic efficiency for detecting N2 metastases was evaluated using receiver operating characteristic (ROC) curves, and a combined diagnostic model was constructed using logistic regression and ROC curve analyses in lung adenocarcinoma (LUAD).Results: There were 16,772 patients in MLND group, and 2,699 cases in no-MLND group. The clinical data from SEER showed that the incidence of N2 metastasis was low in pT1 NSCLC (1,023/16,772, 6.10%), but the prognosis of no-MLND patients was poorer than those who underwent MLND (P<0.001, HR =1.605). Pathological N2 metastasis was correlated with age, histologic type, and tumor size. On the other hand, five lncRNAs (LINC00892, AC099522.2, LINC01481, SCAMP1-AS1, and AC004812.2) were screened and confirmed as potential diagnostic biomarkers for detecting N2 metastasis in pT1 LUAD. The AUC of the combined indicators was 0.857.Conclusions: MLND may be oncologically necessary for selected T1 NSCLC patients based on the

Machine learning-based integration develops an immunogenic cell death-derived lncRNA signature for predicting prognosis and immunotherapy response in lung adenocarcinoma

“…The aberrant upregulation of MIR4435-2HG in LUAD can upregulate related transcription factors and promote the EMT process 49 . LINC00892 has the potential as a biomarker of metastasis in T1 LUAD 50 . LINC00460 is upregulated in the LUAD group and played an important role in the control of oncogenes and tumor suppressors 51 .…”

LINC00669 promotes lung adenocarcinoma growth by stimulating the Wnt/β‐catenin signaling pathway

“… 14 Hao and colleagues found that five lncRNAs ( SCAMP1‐AS1 , LINC00892 , LINC01481 , and AC004812.2 , AC099522.2 ) could be potentially used as diagnostic biological markers for screening N2 metastasis in pT1 lung adenocarcinoma (LUAD). 15 Elevated expression levels of lncRNA LCIIAR foreseen a poor prognosis in lung cancer. 16 Tumor‐suppressing lncRNAs are also reported.…”

“…LncRNA MARCKSL1‐2 was remarkably downregulated in docetaxel (DTX)‐resistant lung adenocarcinoma cells, while overexpression of this lncRNA in tumor cells reversed DTX resistance 14 . Hao and colleagues found that five lncRNAs ( SCAMP1‐AS1 , LINC00892 , LINC01481 , and AC004812.2 , AC099522.2 ) could be potentially used as diagnostic biological markers for screening N2 metastasis in pT1 lung adenocarcinoma (LUAD) 15 . Elevated expression levels of lncRNA LCIIAR foreseen a poor prognosis in lung cancer 16 .…”

Development and validation of a nomogram for predicting overall survival in patients with stage III-N2 lung adenocarcinoma based on the SEER database

“…Lung cancer is the leading cause of cancer-related death worldwide. Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancers, with more than half manifesting histologically as lung adenocarcinoma (LUAD) ( 1 , 2 ). Prognostic factors for LUAD are essential for developing prognostic assessments that might potentially identify patients who will benefit most from aggressive treatment choices while protecting others from the toxicity ( 3 ).…”