Objective: To analyze the expressions of non-small-cell lung cancer (NSCLC) driver genes and their mutation distribution characteristics in the Yunnan-Kweichow plateau, and to provide evidences for personalized molecular targeted therapy of lung cancer in high-incidence areas. Methods: A retrospective analysis was performed on the medical records of patients with NSCLC who underwent combined lung cancer 8 gene detection, including epidermal growth factor receptor (EGFR), rat sarcoma viral oncogene (RAS), anaplastic lymphoma kinase (ALK), RET proto-oncogene (RET), v-Raf murine sarcoma viral oncogene homolog (BRAF), ROS proto-oncogene 1 (ROS1), human epidermal growth factor receptor-2 (HER-2), and cellular-mesenchymal to epithelial transition factor (MET), from January 2016 to August 2019 in Yunnan Cancer Hospital. Besides, we analyzed the expressions of NSCLC driver genes and their mutation distributions. Results: The positive rate of NSCLC driver genes in Yunnan was 67.05%(1 508/2 249). The mutation rates in Xishuangbanna (76.92%), Yuxi (72.38%), Xuanwei (71.88%), Qujing (71.24%), and Honghe (71.79%) were significantly higher than other areas. The mutation rates of Hui (84.38%), Hani (85.00%), Zhuang (75.00%), Buyi (100%), Manchu (100%), Tujia (100%) and Achang (100%) are significantly higher than the minority national average. Driver gene mutations were related to gender (P<0.001), smoking history (P<0.001), age (P<0.001), pathological type (P<0.001), and whether the Xuanwei area (P=0.027), but not related to the nationality (P=0.748) and family history of lung cancer (P=0.676). The mutation rates of EGFR, RAS, BRAF, HER-2 and MET genes were 44.46%, 10.98%, 1.24%, 0.89% and 0.76%, and the rearrangement rates of ALK, RET and ROS1 genes were 4.67%, 1.29% and 0.89%, respectively.The mutation rate of EGFR in females was 56.67%, which was higher than 33.19% in males (P<0.001). The mutation rate of RAS in males was 12.66%, which was higher than 9.17% in females (P=0.010). The mutation rate of RAS in the Han was 11.49%, which was higher than 7.17% in the minority (P=0.032). The rate of RAS mutation in Xuanwei patients was 24.74%, significantly higher than 8.15% in non-Xuanwei area (P<0.001), and the EGFR mutation rate was 40.63%, which was lower than 45.25% in non-Xuanwei area (P=0.045). The rate of ALK rearrangement in Xuanwei patients was 1.56%, which was significantly lower than 5.31% in the non-Xuanwei area (P<0.001), and no HER-2 mutation patients were detected in Xuanwei area. The mutation rate of EGFR in patients with non-smoking history was 51.10%, significantly higher than 29.70% of patients with smoking history (P<0.001). Meanwhile, the rate of ALK rearrangement with non-smoking history patients was 5.35%, which was also higher than 3.16% of patients with smoking history (P<0.001). The rate of RAS mutation in patients with non-smoking history was 9.34%, lower than 14.63% of patients with smoking history (P=0.008). Conclusions: The positive rate of driven gene expression in NSCLC patients from the Yunnan-Kweichow Plateau is slightly lower than the national average. The rates of EGFR and RAS mutations are similar to the domestic average. The rates of ROS1, ALK and RET genes rearrangements and the rates of BRAF, HER2 and MET gene mutations are slightly lower than the national average. EGFR, RAS and ALK genes in the NSCLC patients from Yunnan-Kweichow Plateau have high positive rates, and display different demographic and clinical characteristics, which are of great significance in the selection of targeted therapy populations.
目的： 探讨云贵高原地区非小细胞肺癌(NSCLC)患者驱动基因的表达情况及其突变分布特征，为高发区肺癌的个体化分子靶向治疗提供依据。 方法： 收集云南省肿瘤医院2016年1月至2019年8月收治的行肺癌8基因[表皮生长因子受体(EGFR)、间变性淋巴瘤激酶(ALK)、鼠类肉瘤病毒癌基因(RAS)、RET原癌基因(RET)、鼠肉瘤病毒v-Raft同源致癌基因(BRAF)、肉瘤致癌因子(ROS1)、人表皮生长因子受体2(HER-2)、细胞间质上皮转化因子(MET)]联合检测的2 249例NSCLC患者的临床病理资料，分析云贵高原地区NSCLC驱动基因的表达情况及其突变分布特征。 结果： 云贵高原地区NSCLC驱动基因表达的阳性率为67.05%(1 508/2 249)，其中西双版纳、玉溪、宣威、红河和曲靖地区的阳性率较高，分别为76.92%、72.38%、71.88%、71.79%和71.24%；回族、哈尼族、壮族、布依族、满族、土家族和阿昌族患者的阳性率较高，分别为84.38%、85.00%、75.00%、100%、100%、100%和100%。NSCLC患者驱动基因的阳性率与性别(P<0.001)、吸烟史(P<0.001)、年龄(P<0.001)、病理类型(P<0.001)及是否宣威地区(P＝0.027)有关，与民族(P＝0.748)和肺癌家族史(P＝0.676)无关。EGFR、RAS、BRAF、HER-2和MET基因突变率分别为44.46%、10.98%、1.24%、0.89%和0.76%，ALK、RET、ROS1基因重排率分别为4.67%、1.29%和0.89%。女性患者EGFR突变率为56.67%，高于男性患者(33.19%，P<0.001)；男性患者RAS突变率为12.66%，高于女性患者(9.17%，P＝0.010)。汉族患者RAS突变率为11.49%，高于少数民族患者(7.17%，P＝0.032)。宣威地区患者RAS突变率为24.74%，高于非宣威地区患者(8.15%，P<0.001)；而EGFR突变率为40.63%，低于非宣威地区患者(45.25%，P＝0.045)；ALK重排率为1.56%，低于非宣威地区患者(5.31%，P<0.001)；宣威地区未检出HER-2突变患者。无吸烟史患者EGFR突变率为51.10%，高于有吸烟史患者(29.70%，P<0.001)；无吸烟史患者ALK重排率为5.35%，也高于有吸烟史患者(3.16%，P<0.001)；无吸烟史患者RAS突变率为9.34%，低于有吸烟史患者(14.63%，P＝0.008)。 结论： 云贵高原地区NSCLC驱动基因表达的阳性率略低于全国平均水平，其中EGFR、RAS突变率与国内平均水平相近，ROS1、ALK和RET基因重排率以及BRAF、HER-2和MET基因突变率略低于全国平均水平。EGFR、RAS、ALK基因在云贵高原地区NSCLC患者中阳性率较高，且具有不同的人口学特征和临床特征，在选择靶向治疗人群中具有重要意义。.
Keywords: Driver gene; Lung neoplasms; Targeted therapy; Yunnan-Kweichow Plateau.