Clinicopathological Features and Prognosis of Lung Adenocarcinoma Patients With K-RAS Gene Mutation
Authors: Sun Di , Liu Ying , Li Peng , Yang Ping , Yu GuoHua 
Published: June 2023

Objective:
To investigate the relationship between K-RAS gene mutation and clinicopathological features and prognostic factors in lung adenocarcinoma.

Materials and Methods:
A total of 795 patients with lung adenocarcinoma diagnosed and tested for ten genes from January 1, 2016, to December 31, 2019, were reviewed. One hundred forty patients with K-RAS gene mutation lung adenocarcinoma were screened, of which 82 cases were included in this group, and complete follow-up data were obtained. PD-L1 immunohistochemistry was further performed, and the correlation between K-RAS mutation patients and clinicopathological features and related driver genes was analyzed. The survival curve was drawn by Kaplan-Meier curve. The effects of clinicopathological features on patients’ survival were analyzed by Cox univariate and multivariate analysis.

Results:
The age of onset of 82 patients with K-RAS gene mutation lung adenocarcinoma was 46 to 89 years old, and the median age of onset was 69 years old. There were 64 male patients (78.05%) and 18 female patients (21.95%), including 68 smokers (82.93%). Tumor size: 2 to 5.5 cm, with an average tumor size of 3.5 cm. Histopathologic types: solid type in 60 cases (73.17%), micropapillary type in 2 cases (2.43%), and invasive mucinous type in 20 cases (24.39%). The degree of tumor differentiation: well-differentiated: 0 cases, moderately differentiated: 10 cases (12.20%), poorly differentiated: 72 cases (87.80%). Fifty cases (60.98%), 29 cases (35.37%), 29 cases (35.37%), 59 cases (71.95%), and 35 cases (42.68%) were complicated with nerve invasion, vascular invasion, visceral pleura invasion, lymph node metastasis, and distant organ metastasis, respectively. Among them, distant organ metastasis included 24 cases (68.57%) of bone metastasis and 11 cases (36.67%) of brain metastasis. Tumor Ki-67 proliferation index ≥50%: 54 cases (65.85%). Related driver gene mutations: There were 6 cases (7.31%) with a deletion mutation of exon 19 in EGFR or L858R mutation of exon 21 in EGFR, respectively. Immune factor PD-L1 ≥50%: 65 cases (79.27%). The patients were followed up for 402 to 1221 days, with a median follow-up of 612 days. Thirty-five cases died during the follow-up. The 1-, 3-, and 5-year overall survival rates were 100%, 62.20%, and 57.31%, respectively. Cox univariate analysis showed that the degree of tumor differentiation, vascular invasion, distant organ metastasis, Ki-67 index, deletion mutation of exon 19 in EGFR, and high expression of PD-L1 (≥50%) could all affect the prognosis of patients (P < 0.05). Cox multivariate analysis showed that high expression of PD-L1 (≥50%) was an independent predictor of prognosis in patients with K-RAS gene mutation in lung adenocarcinoma.

Conclusions:
K-RAS mutant lung adenocarcinoma is a malignant tumor with high invasiveness and high mortality. The degree of tumor differentiation, vascular invasion, distant organ metastasis, Ki-67 index, deletion mutation of exon 19 in EGFR, and high expression of PD-L1 (≥50%) in patients with K-RAS mutation lung adenocarcinoma can affect the overall survival time of patients. The high expression of PD-L1 (≥50%) is an independent risk factor affecting the prognosis (survival time).