The Ki-67 Proliferation Index-Related Nomogram to Predict the Response of First-Line Tyrosine Kinase Inhibitors or Chemotherapy in Non-small Cell Lung Cancer Patients With Epidermal Growth Factor Receptor-Mutant Status

Abstract

Background: The correlation between Ki-67 and epidermal growth factor receptor (EGFR)- or Kristen rat sarcoma viral oncogene homolog (KRAS)-mutant status in advanced or postoperative-recurrent non-small cell lung cancer (NSCLC) has fewer studies reported, and the prognostic role of Ki-67 with first-line EGFR-tyrosine kinase inhibitors (TKIs) or chemotherapy remains controversial.Methods: A total of 295 patients were tested for EGFR-mutant status in advanced or postoperative-recurrent NSCLC and received first-line EGFR-TKIs or chemotherapy for treatment. Ki-67 expression was retrospectively analyzed by immunohistochemistry. The Kaplan-Meier method was used to calculate survival rates. The multivariate Cox proportional hazards model was used to generate a nomogram. The established nomogram was validated using the calibration plots.Results: The expression levels of Ki-67 were divided into low (<60%, n = 186) and high (≥60%, n = 109) groups, based on the receiver operating characteristic curve. The expression levels of Ki-67 were found to be higher in patients with KRAS mutations when compared to KRAS wildtype, and EGFR wildtype was higher than EGFR mutations. The median overall survival (OS) of the low Ki-67 expression group was significantly longer than that of the high Ki-67 group, no matter in all NSCLC, EGFR mutations, EGFR wildtype, KRAS-mutant status, EGFR-TKIs, or chemotherapy of patients (P < 0.05). Subgroup analysis showed that the KRAS wildtype or EGFR mutations combine with low Ki-67 expression group had the longest median OS than KRAS mutations or EGFR wildtype combine with Ki-67 high expression group (P < 0.05). In the training cohort, the multivariate Cox analysis identified age, serum lactate dehydrogenase (LDH), serum Cyfra211, EGFR mutations, and Ki-67 as independent prognostic factors, and a nomogram was developed based on these covariates. The calibration curve for predicting the 12-, 24-, and 30-month OS showed an optimal agreement between the predicted and actual observed outcomes.Conclusions: The Ki-67 expression-based nomogram can well predict the efficacy of first-line therapy in NSCLC patients with EGFR- or KRAS-mutant status, high expression levels of Ki-67 correlated with a poor prognosis.

Rapid intraoperative Ki-67 immunohistochemistry for lung cancer using non-contact alternating current electric field mixing

“…By contrast, the presence of KRAS mutations or high expression of Ki-67 are independent predictors of increased risk of local tumor progression and postoperative recurrence in stage I adenocarcinoma [33,34]. As a proliferation index, Ki-67 expression correlates with EGFR and KRAS mutations as well as the efficacy of first-line chemotherapy or EGFR-TKI therapy in advanced or postoperative-recurrent NSCLC [35].…”

Effects of different KRAS mutants and Ki67 expression on diagnosis and prognosis in lung adenocarcinoma

“…The Ki67 marker, which is related to tumor cell proliferation, has been found to be associated with the progression, metastasis, and prognosis of LUAD 37 . In our analysis of clinical patient information, it was observed that age and pathological stage were significantly correlated with the Ki67 IHC index, which is consistent with previous studies.…”

Risk Prediction Model for Synchronous Oligometastatic Non-Small Cell Lung Cancer: Thoracic Radiotherapy May Not Prolong Survival in High-Risk patients

“…Several hematological and clinical factors have been shown to suggest a bad prognosis for lung cancer including hypoalbuminemia (16)(17)(18); increase of C-reactive protein (18,19), lactate dehydrogenase (20), PLR (17,(21)(22)(23), NLR (17,(21)(22)(23)(24), SII (17,21), and tumor biomarkers (20,25); abnormal coagulation and fibrinolysis (26, 27); high T and N stage; liver metastasis; adrenal metastasis (28,29); absence of SMs; smoking history; male; and loss of weight (30). In the present study, 10 variables were included in the Risk-Total formula, and the level of risk score was associated with reduced survival of patients, which was consistentwith previous studies.…”