CCKAR is a biomarker for prognosis and asynchronous brain metastasis of non-small cell lung cancer

Abstract

BackgroundNon-small cell lung cancer (NSCLC) is the most common histological type of lung cancer, and brain metastasis (BM) is the most lethal complication of NSCLC. The predictive biomarkers and risk factors of asynchronous BM are still unknown.Materials and methodsA total of 203 patients with NSCLC were enrolled into our cohort and followed up. The clinicopathological factors such as tumor size, T stage, lymphatic invasion, metastasis and asynchronous BM were investigated. CCKAR expression in NSCLC and resected BM was assessed by IHC, and CCKAR mRNAs in NSCLC and para-tumor tissues were estimated by qRT-PCR. The correlations between CCKAR expression, BM and other clinicopathological factors were assessed by chi-square test, and prognostic significance of CCKAR was estimated by univariate and multivariate analyses.ResultsCCKAR was highly expressed in NSCLC tissues compared with para-tumor tissues. CCKAR expression in NSCLC was significantly associated with asynchronous BM. The BM percentages for NSCLC patients with low and high CCKAR were surprisingly 5.2% and 66.6%, respectively. CCKAR expression and BM were unfavorable factors predicting unfavorable outcome of NSCLC. Moreover, CCKAR expression in NSCLC was an independent risk factor of asynchronous BM.ConclusionsCCKAR is a prognostic biomarker of NSCLC. CCKAR expression in NSCLC is positively associated with asynchronous BM, and is a risk factor of asynchronous BM from NSCLC.

Value and significance of brain radiation therapy during first‐line EGFR‐TKI treatment in lung adenocarcinoma with EGFR sensitive mutation and synchronous brain metastasis: Appropriate timing and technique

“…However, the potential confounding variables, including the number of BM lesions and the prognostic factors according to graded prognostic assessment (GPA), were imbalanced in this study. Several Chinese expert consensus and guidelines recommend the use of SRS to manage BM in NSCLC patients and saving WBI as a salvage measure 13,14 . We hypothesize that SRS may have resulted in a better OS due to the improved accuracy of the technique, leading to less brain toxicity when compared with WBI.…”

“…Several Chinese expert consensus and guidelines recommend the use of SRS to manage BM in NSCLC patients and saving WBI as a salvage measure. 13,14 We hypothesize that SRS may have resulted in a better OS due to the improved accuracy of the technique, leading to less brain toxicity when compared with WBI.…”

“…As a result, there is still no consensus on the use of upfront brain radiotherapy (RT) for patients with syn-BM treated with first-line therapy of EGFR-TKI, especially when either a SRS or third-generation TKI regimen is used. [9][10][11][12][13][14] Several retrospective studies concluded that the use of first-generation TKIs with upfront brain RT improved intracranial progression-free survival (IC-PFS) but did not always result in an improvement in OS when compared with the use of TKIs alone. [15][16][17][18][19][20] Studies based on second and third-generation EGFR-TKIs are limited.…”

“…New third‐generation TKIs and antiangiogenic drugs with higher intracranial activity could further improve the local control for intracranial lesions. As a result, there is still no consensus on the use of upfront brain radiotherapy (RT) for patients with syn‐BM treated with first‐line therapy of EGFR‐TKI, especially when either a SRS or third‐generation TKI regimen is used 9–14 . Several retrospective studies concluded that the use of first‐generation TKIs with upfront brain RT improved intracranial progression‐free survival (IC‐PFS) but did not always result in an improvement in OS when compared with the use of TKIs alone 15–20 .…”

Exploring the Molecular Tumor Microenvironment and Translational Biomarkers in Brain Metastases of Non-Small-Cell Lung Cancer

“…Brain-derived neurotrophic factor (BDNF) levels in primary LUAD have been linked to a heightened risk of brain metastasis development, with brain metastases expressing higher BDNF levels than their primary lesion counterparts [84]. Furthermore, other tissue markers, including cholecystokinin A receptor (CCKAR) and WD repeat domain 5 (WDR5), are significantly associated with brain metastasis and have emerged as independent risk factors [85,86].…”