Correlation between the Expression of VEGF and Ki67 and Lymph Node Metastasis in Non-small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

Abstract

Background. Lymph node metastasis is the most common and important way of metastasis in NSCLC and is also the most important factor affecting lung cancer stage and prognosis. It is very important to analyze the relationship between the expression of vascular endothelial growth factor (VEGF) and Ki67 and lymph node metastasis (LNM) in non-small-cell lung cancer (NSCLC). Methods. We searched the PubMed, EMBASE, and Cochrane Library and conducted meta-analyses using the R meta-package. Relative risk (RR) with a 95% confidence interval (95% CI) was the main indicator. Results. Totally, 18 studies were considered eligible, with 4521 patients, including 1518 LNM-positive patients and 3033 LNM-negative patients. The incidence of LNM in Ki67-negative patients was lower than that in Ki67-positive patients (RR = 0.66, 95% CI: 0.44, 0.98). The incidence of LNM in VEGF-A-negative patients was lower than that in VEGF-A-positive patients (RR = 0.64, 95% CI: 0.49, 0.83). The incidence of LNM in VEGF-C negative patients was lower than that in VEGF-C positive patients (RR = 0.68, 95% CI: 0.53, 0.88). The incidence of LNM in VEGF-D negative and positive patients were of no significant differences (RR = 0.84, 95% CI: 0.61, 1.14). Conclusion. The high expression of Ki67, VEGF-A, and VEGF-C significantly increases the risk of lymph node metastasis in NSCLC, while the VEGF-D expression has no correlation with lymph node metastasis. The expression levels of Ki67, VEGF-A, and VEGF-C show a good potential for lymph node metastasis prediction.

Factors correlating the expression of PD-L1

“…These studies indicated that the GGO predicted favorable OS (overall survival) and DFS (disease-free survival). It has also been revealed that PD-L1 and Ki 67 were correlated with poor prognosis [9,10,51]. Furthermore, LUAD with GGO component has been suggested to have low expression of PD-L1 and Ki67, which were poor prognosis biomarkers.…”

“…Ki67 is a DNA-binding nuclear protein, which is expressed throughout the proliferative phases of the cell cycle and absent in the quiescent (G0) phases [7,8]. Furthermore, the literature suggests that Ki67 is correlated with the prognosis of lung cancer [9,10].…”

Diagnostic Performance of Radiomics in Prediction of Ki-67 Index Status in Non-small Cell Lung Cancer: A Systematic Review and Meta-Analysis

“…It is particularly significant in marking cells in the growth phase and is used to determine tumor cell proportions, linking with rapid tumor growth and a worse prognosis. Specifically in lung cancer, cells expressing Ki-67 exhibit heightened proliferation, greater invasiveness, and a higher likelihood of lymph node metastasis (22). Its higher expression might also be an indicator of shortened progression-free survival (PFS) time (23).…”

Prognostic value of cancer-associated fibroblasts-related genes in lung adenocarcinoma

“…Studies have pointed out that VEGFC mediates angiogenesis through VEGFR-2 and lymphatic metastasis formation through VEGFR-3, playing an important role in tumor angiogenesis and lymphatic metastasis, and its expression is a key indicator for judging tumor type and prognosis ( 41 , 42 ). A meta-analysis ( 43 ) pointed out that the incidence of lymph nodes in NSCLC patients with negative VEGFC was lower than that in patients with positive VEGFC , indicating that the expression level of VEGFC had good potential for predicting lymph node metastasis. This study has also revealed that the overexpression of VEGFC predicts a poor prognosis in patients with lung adenocarcinoma, which is similar to previous studies.…”