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. 2019 Dec;8(6):959-966.
doi: 10.21037/tlcr.2019.12.01.

Cyclin D1 expression as a potential prognostic factor in advanced KRAS-mutant non-small cell lung cancer

Sutima Luangdilok  1   2 , Passakorn Wanchaijiraboon  2 , Poonchavist Chantranuwatana  3 , Chinachote Teerapakpinyo  4 , Shanop Shuangshoti  3   4 , Virote Sriuranpong  2
Affiliations

Cyclin D1 expression as a potential prognostic factor in advanced KRAS-mutant non-small cell lung cancer

Sutima Luangdilok et al. Transl Lung Cancer Res. 2019 Dec.

Abstract

Background: East Asian, including Thailand, lung cancer population may have a relatively lower prevalence of KRAS mutations than Caucasians. We investigated the prevalence and clinical characteristics of KRAS-driven non-small cell lung cancer (NSCLC) patients and the expression of cyclin D1, one of the KRAS downstream targets.

Methods: Lung cancer patients who received treatment at the King Chulalongkorn Memorial Hospital between January 2015 and July 2017 were enrolled. We identified KRAS mutations using allele specific PCR KRAS mutation testing. Cyclin D1 expression was determined using immunohistochemistry.

Results: After excluding 376 EGFR mutations and inadequate samples, we enrolled 95 patients eligible for KRAS mutation testing. KRAS mutations were identified in 28 out of 95 patients. There were 26 patients with KRAS codon 12/13 and 2 patients with KRAS codon 61 mutations. The prevalence of KRAS mutations among informative samples was 28 out of 357 (7.8%) which was relatively lower than that reported in Caucasian population. Smoking and male were significantly associated with KRAS mutations. The prognosis of KRAS-mutant NSCLC patients in particular codon 61 mutations was worse than that found in KRAS- and EGFR-wild-type (KRAS WT/EGFR WT) NSCLC patients (P=0.048). The levels of cyclin D1 expression in KRAS-mutant NSCLC were significantly higher than those in KRAS WT/EGFR WT NSCLC (P=0.02). A better prognosis of KRAS-mutant NSCLC patients with low cyclin D1 expression was observed when compared with those with high cyclin D1 expression (median overall survival 41.7 vs. 3.5 months, P=0.037).

Conclusions: We found a moderate prevalence of KRAS mutations in lung cancer in Thailand. Clinical characteristics were similar to those of Caucasian population. Most KRAS-mutant NSCLC had high cyclin D1 expression. Cyclin D1 expression may serve as a useful prognostic biomarker in KRAS-mutant lung cancer. Validation of this finding in larger cohort is required.

Keywords: East Asia; Kirsten rat sarcoma (KRAS); Non-small cell lung cancer (NSCLC); cyclin D1.

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Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Immunohistochemical staining of cyclin D1 in lung cancer (∇, ▼, ⇣, ↓ represented negative, 1+, 2+, 3+, respectively).
Figure 2
Figure 2
Patient flow diagram. From January 2015 to July 2017, 471 patients with NSCLC were evaluated for EGFR mutation test. There were 262 (55.6%) patients with EGFR mutations and 209 (44.4%) patients without EGFR mutations. After excluding 114 inadequate DNA specimens, 95 patients were evaluable for KRAS mutation testing. NSCLC, non-small cell lung cancer.
Figure 3
Figure 3
Overall survival of NSCLC patients with KRAS mutation vs. KRAS WT/EGFR WT. NSCLC, non-small cell lung cancer; WT, wild type.
Figure 4
Figure 4
XXXXXXX. (A) Cyclin D1 expression in KRAS-mutant lung cancer (n=24) was significantly higher than those in KRAS WT/EGFR WT lung cancer (n=26); (B,C) overall survival of stage IV NSCLC patients with low cyclin D1 vs. high cyclin D1 in KRAS mutation (n=18) (B) and KRAS WT/EGFR WT (n=19) (C) (log-rank; P=0.037 for KRAS mutation and P=0.645 for KRAS WT/EGFR WT). NSCLC, non-small cell lung cancer; WT, wild type.
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