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. 2020 May;9(5):3491-3498.
doi: 10.21037/tcr.2020.03.72.

Analysis of the relationship between Ki-67 expression and chemotherapy and prognosis in advanced non-small cell lung cancer

Diming Wang  1   2 , Dongmei Chen  2 , Chi Zhang  2 , Mei Chai  2 , Maojing Guan  2 , Zhongyu Wang  2 , Ye Wei  3 , Yiwen Zhang  4 , Qingming Shi  2 , Kangsheng Gu  1
Affiliations

Analysis of the relationship between Ki-67 expression and chemotherapy and prognosis in advanced non-small cell lung cancer

Diming Wang et al. Transl Cancer Res. 2020 May.

Abstract

Background: To analyse the relationship between the Ki-67 index of advanced non-small cell lung cancer (NSCLC) and the objective response rate (ORR) and progression-free survival (PFS) of patients who received chemotherapy.

Methods: The Ki-67 index of advanced NSCLC pathology was established by immunohistochemistry; using univariate and multivariate analyses, we retrospectively analysed the relationship between the Ki-67 index of 112 advanced NSCLC patients in our hospital and chemotherapy response and PFS. Both epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) were found to be wild type in adenocarcinoma patients, and no gene testing was performed for those with squamous cell carcinoma. All selected patients received four cycles of platinum-based chemotherapy, and according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1), the curative effect was evaluated after every two cycles.

Results: In the univariate and multivariate analyses, the Ki-67 index was significantly associated with the objective response to chemotherapy (B =-0.069, P=0.000). Ki-67 expression could also accurately predict the ORR of chemotherapy [P<0.0001, area under the curve (AUC) =0.7467, 95% confidence interval (CI): 0.6578-0.8356]: squamous cell carcinoma group [P=0.0003, AUC =0.8065 (95% CI: 0.6922-0.9208)], adenocarcinoma group [P=0.0193, AUC =0.6810 (95% CI: 0.5360-0.8262)]. The overexpression of Ki-67 was a negative prognostic factor for PFS in advanced NSCLC (P<0.0001): squamous cell carcinoma (P=0.0055), adenocarcinoma (P<0.0001). According to the multivariate Cox analysis, Ki-67 index (P=0.000) and stage (P=0.001) were negative factors of PFS.

Conclusions: The Ki-67 index might be a clinically significant biomarker in advanced NSCLC and may be able to predict the efficacy of chemotherapy. High expression of Ki-67 might also be an indicator of shortened PFS time.

Keywords: Ki-67 index; advanced non-small cell lung cancer (advanced NSCLC); chemotherapy; objective response rate (ORR); progression-free survival (PFS).

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr.2020.03.72). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
High Ki-67 index predicts significant response to chemotherapy. (A) The area under the receiver operating characteristic (ROC) curve using the Ki-67 index to predict the accuracy of the objective therapeutic effect of chemotherapy is shown in the entire experimental group; (B) the area under the ROC curve is shown in the adenocarcinoma (ADC) group; (C) the area under the ROC curve is shown in the squamous cell carcinoma (SQCC) group. CR, complete remission; PR, partial remission; SD, stable disease; PD, progressive disease; AUC, area under the curve.
Figure 2
Figure 2
Low Ki-67 level in squamous cell carcinoma (SQCC) and adenocarcinoma (ADC) is associated with better survival. Kaplan-Meier curves for progression-free survival (PFS) according to the Ki-67 high expression group and the Ki-67 low expression group. (A) Overall population; (B) adenocarcinoma; (C) squamous cell carcinoma.
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