Abstract: Objective　To explore the clinical features and survival prognosis of stage Ⅳ non-small cell lung cancer (NSCLC) and provide a reference for prognosis evaluation and prevention and treatment of the disease. Methods A retrospective analysis was performed on 195 patients with stage Ⅳ NSCLC admitted to the Department of Medical Oncology and the Department of Respiratory Medicine of the First Affiliated Hospital of Hainan Medical University from 2016 to 2020, who were diagnosed pathologically and available for the analysis and study. Patients' hospitalization records and follow-up information were collected to analyze the survival of the patients at the cut-off of follow-up. The Kaplan-Meier method was used to calculate survival rates, and the Log-rank method was employed for univariate analysis of factors affecting survival. The risk factors for patients' survival prognosis were analyzed by multivariate Cox regression model. Results The median survival time for patients with stage Ⅳ NSCLC was 17.05 months (95% CI: 12.64-21.45), with cumulative survival rates of 70.7%, 41.5%, and 22.0% at 1, 2, and 3 years, respectively. The results of multivariate analysis suggested that gender (HR=0.697, 95% CI: 0.486-0.999, P=0.049), functional status scale (Karnofsky, KPS) (HR=1.535, 95% CI: 1.038-2.270, P=0.032), computed tomography (CT) tumor location (HR=1.481, 95%CI:1.003-2.186, P=0.036), pathology type (HR=1.181, 95%CI:0.715-1.950, P=0.019), metastatic site (HR=1.710, 95%CI:1.214-2.409, P=0.002), N stage (HR=2.094, 95%CI:0.973-4.509, P=0.006), gene mutation (HR=2.387, 95%CI:1.590-3.584, P<0.001), treatment with chemotherapy-containing regimen (HR=1.713, 95%CI:1.094-2.683, P= 0.019), and combination therapy (HR=1.874, 95%CI:1.253-2.802, P=0.002) were independent prognostic factors affecting the survival of patients with stage Ⅳ NSCLC (all P<0.05). In the subgroup analysis, metastatic site and chemotherapy-containing treatment regimen were independent prognostic factors affecting the survival of mutation-positive patients with stage Ⅳ NSCLC, and patients who received targeted therapy had longer survival time. The metastatic site, chemotherapy-containing treatment regimen, and combination therapy were prognostic factors affecting the survival prognosis of patients with gene mutation-negative stage Ⅳ NSCLC or unknown status. Conclusions In this study, gender, KPS score, CT tumor location, pathologic type, metastatic site, N stage, gene mutation, treatment with chemotherapy-containing regimen, and combination therapy were the important factors affecting the survival prognosis of patients with stage Ⅳ NSCLC. In terms of treatment options, chemotherapy remains an indispensable basic treatment option. Moreover, comprehensive treatment can prolong survival compared to a single treatment option. Patients with positive gene mutations who received targeted drugs had longer survival times; therefore, detecting gene mutation status and selecting corresponding targeted drugs in the treatment of stage Ⅳ NSCLC could extend survival periods.

This study aims to investigate the function of two SNPs (rs8904C > T and rs696G >A) in 3' untranslated region (3'UTR) of NFKBIA gene by constructing luciferase reporter gene. A patient's genomic DNA with rs8904 CC and rs696 GA genotype was used as the PCR template. Full-length 3'UTR of NFKBIA gene was amplified by different primers. After sequencing validation, these fragments were inserted to the luciferase reporter vector, pGL3-promoter to construct recombinant plasmids containing four kinds of haplotypes, pGL3-rs8904C/rs696G, pGL3-rs8904C/rs696A, pGL3-rs8904T/rs696G and pGL3-rs8904T/rs696A. Then these plasmids were transfected into LS174T cells and the luciferase activity was detected. Compared with pGL3-vector transfected cells (negative control), the luciferase activity of the four kinds of recombinant plasmids was significantly decreased (P < 0.001). For rs696G > A, the luciferase activity of the recombinant plasmids containing A allele (pGL3-rs8904C/rs696A and pGL3-rs8904T/rs696A) was about 45.1% (P < 0.05) and 56.1% (P < 0.001) lower than those containing G allele (pGL3-rs8904C/rs696G and pGL3-rs8904T/rs696G), respectively. For rs8904C > T, there were no significant differences in the luciferase activity between the recombinant plasmids containing T allele and those with C allele. Together, the luciferase reporter gene vectors containing SNPs in NFKBIA gene 3'UTR were constructed successfully and rs696G > A could decrease the luciferase activity while rs8904C >T didn't have much effect on the luciferase activity.