Predictive Value of KIAA1199 and Linc00673 Genes on Chemotherapy Efficacy in Non-small Cell Lung Cancer
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摘要:
目的 探讨KIAA1199基因和Linc00673基因在非小细胞肺癌患者化疗前后的表达变化，并进一步评估这两个基因作为分子标志物在预测化疗疗效方面的潜在价值。 方法 选取2019年8月至2021年8月石家庄市第三医院和华北医疗健康集团峰峰总医院收治的58 例Ⅲ-Ⅳ期非小细胞肺癌患者，分别在治疗前2d和治疗两个周期后获取患者外周血PBMC细胞，检测KIAA1199基因、Linc00673基因表达水平，统计患者化疗疗效，并通过ROC曲线分析KIAA1199基因、Linc00673基因作为分子标志物预测化疗疗效的价值。 结果 经两个周期化疗后，58例患者中20例出现病情进展，占比34.48%。qPCR结果显示，治疗前，进展与未进展患者间KIAA1199基因、Linc00673基因表达水平比较，差异均无统计学意义（P > 0.05）；治疗后，相比于进展患者，未进展患者KIAA1199基因、Linc00673基因表达水平均显著降低（P < 0.01）。ROC曲线分析结果显示，联合检测的AUC均显著高于KIAA1199基因和Linc00673基因（Z = 3.054、5.178，P < 0.05）。 结论 在非小细胞肺癌化疗患者中，KIAA1199基因、Linc00673基因的表达因疗效不同而呈现显著差异，其中KIAA1199基因更适宜作为预测化疗疗效的生物标志物。 Abstract:Objective To explore the expression changes of KIAA1199 and Linc00673 genes in non-small cell lung cancer patients before and after chemotherapy, and to further evaluate the potential value of these two genes as molecular markers in predicting chemotherapy efficacy. Methods : A total of 58 patients with stage Ⅲ-Ⅳ NSCLC admitted to the Third Hospital of Shijiazhuang and Fengfeng General Hospital of North China Medical Health Group from August 2019 to August 2021 were selected. Peripheral blood PBMCs were collected from patients 2 days before treatment and after two cycles of treatment to detect the expression levels of KIAA1199 and Linc00673 genes. The chemotherapy efficacy of patients was statistically analyzed, and the value of KIAA1199 and Linc00673 genes as molecular markers in predicting chemotherapy efficacy was assessed using ROC curve analysis. Results After 2 cycles of chemotherapy, 20 out of 58 patients showed disease progression, accounting for 34.48%. qPCR results showed no statistically significant difference in the expression levels of KIAA1199 and Linc00673 genes between progressed and non-progressed patients before treatmen （P > 0.05）. After treatment, the expression levels of KIAA1199 and Linc00673 genes were significantly lower in non-progressed patients compared to progressed patients （P < 0.01）. ROC curve analysis showed that the AUC of combined detection was significantly higher than that of KIAA1199 gene and Linc00673 gene alone （Z = 3.054, 5.178, P < 0.05）. Conclusion In NSCLC patients undergoing chemotherapy, the expression of KIAA1199 and Linc00673 genes shows significant differences based on therapeutic efficacy, with KIAA1199 being more suitable as a biomarker for predicting chemotherapy efficacy. -
Key words:
- Linc00673 /
- KIAA1199 /
- Non small cell lung cancer /
- Expression level /
- Efficacy prediction
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图 1 化疗前后两组患者外周血KIAA1199基因和Linc00673基因相对表达量分析
A：治疗前后进展组和未进展组KIAA1199相对表达量比较；B：治疗前后进展组和未进展组Linc00673相对表达量比较；与进展组比较，**P < 0.01。
Figure 1. Analysis of the relative expression levels of KIAA1199 and Linc00673 in the peripheral blood of the two groups of patients before and after chemotherapy
图 2 ROC曲线分析KIAA1199基因和Linc00673基因作为分子标志物的预测效果
Figure 2. ROC curve analysis of the predictive effects of KIAA1199 and Linc00673 as molecular markers
表 1 qPCR检测中不同基因的引物序列
Table 1. The primer sequences of different genes in qPCR detection
基因名 引物序列（5'-3'） KIAA1199 正向序列：5′-GCCTGTGGCCTATGCAGTCA-3′ 反向序列：5′-TGCTGTGGCCTGTTCCCACTGCTTAC-3' Linc00673 反向序列: 5′-AATATTAAACGGTCCAGTCCTACAA-3′ 反向序列: 5′-TAGGACTGCCCATTACAGAGGA-3′ GAPDH 正向序列: 5′-CGACTTATACATGGCCTTA-3′ 反向序列: 5′-TTCCGATCACTGTTGGAAT-3′ 
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表 2 患者一般资料比较
Table 2. Comparison of general data of patients
临床病理特征 无进展组
（n = 38）进展组
（n = 20）χ2 P 年龄（岁） 1.277 0.258 < 65 15（39.47） 11（55.00） ≥ 65 23（60.53） 9（45.00） 性别 0.043 0.836 男 32（84.21） 18（90.00） 女 6（15.79） 2（10.00） 吸烟史 0.547 0.460 有 27（71.05） 16（80.00） 无 11（28.95） 4（20.00） TNM分期 3.471 0.062 Ⅲ期 21（55.26） 11（55.00） Ⅳ期 17（44.74） 9（45.00） 病理类型 鳞癌 18（47.37） 10（50.00） 0.036 0.849 腺癌 17（44.74） 9（45.00） 0.000 0.985 其他 3（7.89） 1（5.00） 0.017 0.895
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表 3 患者化疗疗效分析
Table 3. Analysis of the efficacy of chemotherapy in patients
临床病理特征 n 百分比（%） CR 0 0 PR 13 22.4 SD 25 43.1 PD 20 34.4
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表 4 ROC曲线分析KIAA1199基因和Linc00673基因对化疗疗效的预测价值
Table 4. ROC curve analysis of the predictive value of KIAA1199 gene and Linc00673 gene for chemotherapy efficacy
指标 曲线下面积（95%CI） 敏感度（%） 特异度（%） 截断值 约登指数 KIAA1199基因 0.829（0.726～0.932） 90.0（18/20） 31.6（12/38） > 1.270 0.584 Linc00673基因 0.758（0.637～0.878） 100.0（20/20） 52.6（20/38） > 0.955 0.474 联合检测 0.880（0.793～0.966） 100.0（20/20） 26.3（10/38） − 0.737
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[1] Tang A,Ahmad U,Toth AJ,et al. Non-small cell lung cancer in never- and ever-smokers: Is it the same disease? [J]. J Thorac Cardiovasc Surg,2021,161(6): 1903-1917. e9. [2] Alexander M,Kim S Y,Cheng H Y. Update 2020: Management of non-small cell lung cancer[J]. Lung,2020,198(6):897-907. doi: 10.1007/s00408-020-00407-5 [3] Zhou C C,Chen G Y,Huang Y C,et al. Camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in chemotherapy-naive patients with advanced non-squamous non-small-cell lung cancer (CameL): A randomised,open-label,multicentre,phase 3 trial[J]. Lancet Respir Med,2021,9(3):305-314. doi: 10.1016/S2213-2600(20)30365-9 [4] Imyanitov E N,Iyevleva A G,Levchenko E V. Molecular testing and targeted therapy for non-small cell lung cancer: Current status and perspectives[J]. Crit Rev Oncol Hematol,2021,157:103194. doi: 10.1016/j.critrevonc.2020.103194 [5] Redman M W,Papadimitrakopoulou V A,Minichiello K,et al. Biomarker-driven therapies for previously treated squamous non-small-cell lung cancer (Lung-MAP SWOG S1400): A biomarker-driven master protocol[J]. Lancet Oncol,2020,21(12):1589-1601. doi: 10.1016/S1470-2045(20)30475-7 [6] Ito K,Nishida Y,Ikuta K,et al. Overexpression of KIAA1199,a novel strong hyaluronidase,is a poor prognostic factor in patients with osteosarcoma[J]. J Orthop Surg Res,2021,16(1):439. doi: 10.1186/s13018-021-02590-4 [7] Liu JM,Yan W,Han P,et al. The emerging role of KIAA1199 in cancer development and therapy[J]. Biomed Pharmacother,2021,138:111507. doi: 10.1016/j.biopha.2021.111507 [8] Qiao K,Ning S P,Wan L,et al. LINC00673 is activated by YY1 and promotes the proliferation of breast cancer cells via the miR-515-5p/MARK4/Hippo signaling pathway[J]. J Exp Clin Cancer Res,2019,38(1):418 doi: 10.1186/s13046-019-1421-7 [9] Lu W,Zhang H H,Niu Y Q,et al. Long non-coding RNA linc00673 regulated non-small cell lung cancer proliferation,migration,invasion and epithelial mesenchymal transition by sponging miR-150-5p[J]. Mol Cancer,2017,16(1):118. doi: 10.1186/s12943-017-0685-9 [10] Guan H Y,Zhu T,Wu S S,et al. Long noncoding RNA LINC00673-v4 promotes aggressiveness of lung adenocarcinoma via activating WNT/β-catenin signaling[J]. Proc Natl Acad Sci U S A,2019,116(28):14019-14028. doi: 10.1073/pnas.1900997116 [11] Schrank B R,Colbert L E. Genomic biomarkers predict response to combined ATR inhibition and radiotherapy[J]. Clin Cancer Res,2024. [12] Ebrahimpour L,Lemaréchal Y,Yolchuyeva S,et al. The impact of radiomics libraries and gray level discretization on the discovery of immunotherapy biomarkers in NSCLC patients[J] . Br J Radiol,2024: tqae187. [13] Tang Z Y,Ding Y,Shen Q,et al. KIAA1199 promotes invasion and migration in non-small-cell lung cancer (NSCLC) via PI3K-Akt mediated EMT[J]. J Mol Med (Berl),2019,97(1):127-140. doi: 10.1007/s00109-018-1721-y [14] Baran K,Kordiak J,Jabłoński S,et al. Panel of miR-150 and linc00673,regulators of CCR6/CCL20 may serve as non-invasive diagnostic marker of non-small cell lung cancer[J]. Scientific Reports,2023,13(1):9642-9642. doi: 10.1038/s41598-023-36485-7 [15] Yao Y,Zhao Q,Xu F,et al. Enhanced anti-tumor therapy for hepatocellular carcinoma via sorafenib and KIAA1199-siRNA co-delivery liposomes[J]. Saudi Pharm J,2024,32(9):102153. doi: 10.1016/j.jsps.2024.102153 [16] Zhu YR,Zhang ZF,Peng H,et al. Clinicopathological and prognostic significance of LINC00673 in human malignancy: A review and meta-analysis[J]. Biosci Rep,2021,41(7):BSR20211175. doi: 10.1042/BSR20211175 [17] Shen X J,Mo X C,Tan W D,et al. KIAA1199 correlates with tumor microenvironment and immune infiltration in lung adenocarcinoma as a potential prognostic biomarker[J]. Pathol Oncol Res,2022,28:1610754. doi: 10.3389/pore.2022.1610754 [18] Zhang Y B,Yu H L,Guo Z. Circ_KIAA1199 inhibits MSI1 degradation by targeting miR-34c-5p to drive the malignant cell behaviors and tumor growth of colorectal cancer[J]. Anticancer Drugs,2022,33(1):e134-e144. doi: 10.1097/CAD.0000000000001164 [19] Zhu K J,Gong Z J,Li P C,et al. A review of linc00673 as a novel lncRNA for tumor regulation[J]. Int J Med Sci,2021,18(2):398-405. doi: 10.7150/ijms.48134 [20] Shen S Y,Yang C Q,Liu X B,et al. RBFOX1 regulates the permeability of the blood-tumor barrier via the LINC00673/MAFF pathway[J]. Mol Ther Oncolytics,2020,17:138-152. doi: 10.1016/j.omto.2020.03.014 [21] Li N,Cui Z G,Huang D Y,et al. Association of LINC00673 rs11655237 polymorphism with cancer susceptibility: A meta-analysis based on 23478 subjects[J]. Genomics,2020,112(6):4148-4154. doi: 10.1016/j.ygeno.2020.07.015 [22] Wang S S,Chao J S,Wang H,et al. Effectiveness,safety,and biomarker analysis of lenvatinib plus toripalimab as chemo-free therapy in advanced intrahepatic cholangiocarcinoma: A real-world study[J]. Cancer Immunol Immunother,2024,73(12):249. doi: 10.1007/s00262-024-03841-z [23] Zhou C C,Hu Y P,Arkania E,et al. 152P Exploratory biomarker analysis of phase Ⅲ ASTRUM-004 study: Serplulimab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer[J]. Annals of Oncology,2024,35(S2):S276-S276. [24] Solomon B,Wu L Y,Dziadziuszko R,et al. 1206MO ALINA: Exploratory biomarker analyses in patients (pts) with resected ALK+ non-small cell lung cancer (NSCLC) treated with adjuvant alectinib vs chemotherapy (chemo)[J]. Annals of Oncology,2024,35(S2):S775-S775. -
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