Association between EGFR/KRAS mutation and expression of VEGFA, VEGFR and VEGFR2 in lung adenocarcinoma

Yuan, Xianglin; Yang, Jie; Wang, Xin‐Yue; Xiao-ling, Zhang; Qin, Tingting; Li, Kai

doi:10.3892/ol.2018.8901

Cited by 17 publications

(19 citation statements)

References 39 publications

(34 reference statements)

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“…Recently, some clinical trials (6, 9) of PD-1/PD-L1 inhibitors have demonstrated durable clinical benefit in many patients. Several studies reported that the expression of PD-L1 is closely related to EGFR (18) mutations, KRAS (19) mutations, smoking history (19) and advanced tumor stage (18, 20), but we failed to define a significant correlation between PD-L1 expression and these clinical features in LADC, which is concordant with the results of other studies (20, 21). In addition, some studies suggested that VEGFA expression has a significant association with EGFR mutations, advanced clinical stage and lymph node metastasis (21).…”

Section: Discussionsupporting

confidence: 90%

PD-L1 Expression Is Associated With VEGFA and LADC Patients' Survival

et al. 2019

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Objectives: To elucidate the relationship between VEGFA and PD-L1 expression in lung adenocarcinoma (LADC). Methods: PD-L1 and VEGFA expression were determined by immunohistochemistry with H-score on formalin-fixed paraffin-embedded resected LADC specimens of 129 cases. Results: High PD-L1 expression in 53 (41.1%) patients, high VEGFA expression in 65 (50.4%), and co-expression in 18 (14.0%) were observed. Inverse correlation between expression of PD-L1 and VEGFA was found ( P = 0.002, r = −0.274). VEGFA and PD-L1 expression were not significantly associated with the clinicopathological features. High PD-L1 expression was significantly association with all patients' poor progression-free survival and overall survival in a univariate analysis, but there was no significantly association with high VEGFA expression and prognosis. Co-expression of PD-L1 and VEGFA exhibited a worst overall survival compared to negative groups ( P = 0.005). Conclusions: These findings indicate that high PD-L1 expression could impact both poor overall survival and progression-free survival in patients with resected LADC. Co-expression of PD-L1 and VEGFA may be considered as an important prognostic factor for patients with resected lung adenocarcinoma.

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Section: Discussionsupporting

confidence: 90%

PD-L1 Expression Is Associated With VEGFA and LADC Patients' Survival

et al. 2019

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“…To date, there is little evidence on the role of KRAS status in D+R therapy (30). Although KRAS mutations might increase the expression of VEGF, VEGFR1 and VEGFR2 in various tumors including NSCLC, the underlying mechanisms is still unclear (31)(32)(33). In vitro data of ramucirumab showed inferior tumor regression in a KRAS mutated xenograft tumor (NCI-H2122) which could be significantly increased by the combination of ramucirumab with a pan-RAF inhibitor (34).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of docetaxel plus ramucirumab as palliative second-line therapy following first-line chemotherapy plus immune-checkpoint-inhibitor combination treatment in patients with non-small cell lung cancer (NSCLC) UICC stage IV

Brueckl¹,

Reck²,

Rittmeyer³

et al. 2021

Transl Lung Cancer Res

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Background: Chemotherapy plus immune-checkpoint inhibitor (CTx+ICI) therapy has become the preferred 1st line treatment in patients with metastatic NSCLC without oncogenic driven mutations.However, the optimal subsequent 2nd line treatment is not defined and several alternatives exist. The purpose of this analysis was to evaluate the efficacy of 2nd line docetaxel plus ramucirumab (D+R) initiated after failure of 1st line CTx+ICI.Methods: Retrospective data were collected during routine care from German thoracic oncology centers.Only patients who had received at least one course of 2nd line D+R were included. ORR, PFS, OS and numbers of courses of D+R were investigated with PFS after initiation of D+R being the primary endpoint.Results: Seventy-seven patients met the inclusion criteria. 2nd line treatment with D+R achieved an ORR and DCR of 32.5% and 62.4%, respectively. Median PFS for 2nd line therapy was 3.9 months with a DOR of 6.4 months. Median OS of 15.5 and 7.5 months were observed from the start of 1st line therapy and 2nd line treatment, respectively. No unexpected toxicities occurred. Presence of KRAS mutations was associated with significantly worse median PFS to D+R (2.8 vs. 4.5 months in wild-type cases; P=0.021) and was an independent predictor of inferior PFS in multivariate analysis.Conclusions: D+R is an effective and safe 2nd line treatment after failure of 1st line CTx+ICI irrespective of NSCLC histology. However, patients with a KRAS mutation did not benefit from D+R in terms of PFS

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“…Hypoxia is proposed as a mechanism of resistance to anti-EGFR therapies that could be reversed [ 122 , 123 , 124 , 125 , 126 ]. For example, Yuan et al explored associations between angiogenesis-inducible factor expressions and the presence of EGFR and KRAS (Kirsten ras oncogene homolog) mutations to specify the relationship between oncogenic alterations and hypoxia [ 127 ]. EGFR mutations concerning 21 or 20 exons ( p = 0.002) were associated with significantly high levels of VEGF-A.…”

Section: Biological Features Associated With Hypoxia In Nsclcmentioning

confidence: 99%

Hypoxia in Lung Cancer Management: A Translational Approach

Ancel

Perotin

Dewolf

et al. 2021

Cancers

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Lung cancer represents the first cause of death by cancer worldwide and remains a challenging public health issue. Hypoxia, as a relevant biomarker, has raised high expectations for clinical practice. Here, we review clinical and pathological features related to hypoxic lung tumours. Secondly, we expound on the main current techniques to evaluate hypoxic status in NSCLC focusing on positive emission tomography. We present existing alternative experimental approaches such as the examination of circulating markers and highlight the interest in non-invasive markers. Finally, we evaluate the relevance of investigating hypoxia in lung cancer management as a companion biomarker at various lung cancer stages. Hypoxia could support the identification of patients with higher risks of NSCLC. Moreover, the presence of hypoxia in treated tumours could help clinicians predict a worse prognosis for patients with resected NSCLC and may help identify patients who would benefit potentially from adjuvant therapies. Globally, the large quantity of translational data incites experimental and clinical studies to implement the characterisation of hypoxia in clinical NSCLC management.

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Association between EGFR/KRAS mutation and expression of VEGFA, VEGFR and VEGFR2 in lung adenocarcinoma

Cited by 17 publications

References 39 publications

PD-L1 Expression Is Associated With VEGFA and LADC Patients' Survival

PD-L1 Expression Is Associated With VEGFA and LADC Patients' Survival

Efficacy of docetaxel plus ramucirumab as palliative second-line therapy following first-line chemotherapy plus immune-checkpoint-inhibitor combination treatment in patients with non-small cell lung cancer (NSCLC) UICC stage IV

Hypoxia in Lung Cancer Management: A Translational Approach

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