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Research ArticleOriginal Article
Open Access

Specific association of MTHFD1 expressions with small cell lung cancer development and chemoradiotherapy outcome

Yujia Hao, Ruichun Lu, Ying Guo and Pengtao Bao
Saudi Medical Journal August 2024, 45 (8) 783-790; DOI: https://doi.org/10.15537/smj.2024.45.8.20230990
Yujia Hao
From the Department of Respiratory Medicine Second Ward (Hao), JinanThird People’s Hospital, Jinan, from the Department of Cadre Healthcare/Geriatrics (Lu), Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, from the Hebei North University (Guo), Zhangjiakou, and from the Department of Pulmonary and Critical Care Medicine (Bao), The Eighth Medical Center of Chinese PLA General Hospital, Beijing, China.
MD, MS
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Ruichun Lu
From the Department of Respiratory Medicine Second Ward (Hao), JinanThird People’s Hospital, Jinan, from the Department of Cadre Healthcare/Geriatrics (Lu), Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, from the Hebei North University (Guo), Zhangjiakou, and from the Department of Pulmonary and Critical Care Medicine (Bao), The Eighth Medical Center of Chinese PLA General Hospital, Beijing, China.
MD, PhD
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Ying Guo
From the Department of Respiratory Medicine Second Ward (Hao), JinanThird People’s Hospital, Jinan, from the Department of Cadre Healthcare/Geriatrics (Lu), Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, from the Hebei North University (Guo), Zhangjiakou, and from the Department of Pulmonary and Critical Care Medicine (Bao), The Eighth Medical Center of Chinese PLA General Hospital, Beijing, China.
MD, BS
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Pengtao Bao
From the Department of Respiratory Medicine Second Ward (Hao), JinanThird People’s Hospital, Jinan, from the Department of Cadre Healthcare/Geriatrics (Lu), Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, from the Hebei North University (Guo), Zhangjiakou, and from the Department of Pulmonary and Critical Care Medicine (Bao), The Eighth Medical Center of Chinese PLA General Hospital, Beijing, China.
MD, PhD
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  • ORCID record for Pengtao Bao
  • For correspondence: [email protected]
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  • Figure 1
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    Figure 1

    - Differential transcripts between small cell lung cancer (SCLC) and lung squamous cell carcinoma (LUSC), and between SCLC and lung adenocarcinoma (LUAD), and the overlapping targets based on the GSE40275 dataset. The volcano maps showing the differential transcripts between A) SCLC and LUSC; and B) between SCLC and LUSC, based on the GSE40275 dataset. The GEO2R tool was used to identify differentially expressed genes. The Venn diagram showing the overlapped C) up-regulated transcripts; and D) down-regulated transcripts among the differential transcripts described in A & B. E) GO enrichment of the overlapped differentially expressed transcripts described in C & D. The plot was calculated and drawn by Metascape Gene List Analysis. LUSC: lung squamous cell carcinoma, LUAD: lung adenocarcinoma, SCLC: small cell lung cancer

  • Figure 2
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    Figure 2

    - MTHFD1 was higher expressed in small cell lung cancer (SCLC) tissues than lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) tissues. Comparing the mRNA levels of DNMT1, MAT2A, HDAC5, METTL3, MECP2, and MTHFD1 between: A) SCLC tissues (n=6) and LUSC tissues (n=6); and B) between SCLC tissues (n=6) and LUAD tissues (n=6) in a small-scale samples. C) Comparing the MTHFD1 levels between tumor tissues and matched adjacent tissues in LUSC (left, n=56), LUAD (middle, n=70), and SCLC (right, n=70) cases in a large-scale samples. D) Comparing the MTHFD1 levels in tissues from healthy controls (HCs, n=33), LUSC (n=56), LUAD (n=70), and SCLC (n=70) cases in a large-scale samples. E-I) The receiver operating characteristic curve for the MTHFD1 levels in distinguishing: E) LUSCs and HCs; F) LUADs and HCs; G) SCLCs and HCs; H) SCLC and LUSCs; and I) SCLC and LUADs. Left: representative stained images among these 4 groups, right: bar chart comparison of differences among these 4 groups, HCs: healthy controls, LUSC: lung squamous cell carcinoma, LUAD: lung adenocarcinoma, SCLC: small cell lung cancer

  • Figure 3
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    Figure 3

    - MTHFD1 levels were specifically associated with prognosis of small cell lung cancer (SCLC) patients after chemoradiotherapy treatment. Kaplan-Meier curves for time to 2-year overall survival of patients with: A) SCLC; B) lung squamous cell carcinoma; and C) lung adenocarcinoma according to MTHFD1 levels. LUSC: lung squamous cell carcinoma, LUAD: lung adenocarcinoma, SCLC: small cell lung cancer, OS: overall survival

  • Figure 4
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    Figure 4

    - Overexpression of MTHFD1 increases radio-resistance in both small cell lung cancer and non-small cell lung cancer in vitro. A) MTHFD1 levels were determined in H69, A549, and BEAS-2B cells. B-C) The H69 and A549 cells were instantly transfected with MTHFD1 over-expressed plasmid for 24 hours, and then the viable cells of B) H69; and C) A549 were detected after treated by different dose irradiation. D-E) The H69 and A549 cells were instantly transfected with MTHFD1 over-expressed plasmid and control plasmid for 24 hours, and then the apoptosis rate of B) H69; and C) A549 were detected after treated by different dose irradiation.

Tables

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    Table 1

    - Clinical indications for included lung cancer patients.

    VariablesLC (n=196)HC (n=33)
    Age
    Above 60121 (61.7)20 (60.6)
    Below 6075 (38.3)13 (39.4)
    Gender
    Male139 (70.9)20 (60.6)
    Female57 (29.1)13 (39.4)
    T stage
    1-294 (48.0)---
    3-4102 (52.0)---
    Metastases
    LM
    Yes145(74.0)---
    No51 (26.0)---
    DM
    Yes96 (48.9)---
    No100 (51.1)---
    Tumor subtype
    LUAD70 (35.7)---
    LUSC56 (28.6)---
    SCLC70 (35.7)---

    Values are presented as numbers and percentages (%). LC: lung cancer, LUAD: lung adenocarcinoma, LUSC: lung squamous cell carcinoma, SCLC: small cell lung cancer, LM: lymphatic metastasis, DM: distant metastasis

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      Table 2

      - Association of MTHFD1 levels with clinical indications for small cell lung cancer, lung squamous cell carcinoma and lung adenocarcinoma patients.

      VariablesSCLC (n=70)LUSC (n=56)LUAD (n=70)
      MTHFD1 high (n=31)MTHFD1 low (n=39)P-valuesMTHFD1 high (n=22)MTHFD1 low (n=34)P-valuesMTHFD1 high (n=25)MTHFD1 low (n=45)P-values
      T stage
      1-29 (29.0)25 (64.1)0.0039 (40.9)20 (50.8)0.1908 (32.0)25 (55.6)0.058
      3-422 (71.0)14 (35.9)13 (59.1)14 (41.2)17 (68.0)20 (44.4)
      Metastases
      LM
      Yes25 (80.6)27 (69.2)0.27818 (81.8)26 (76.5)0.63420 (80.0)29 (64.4)0.173
      No6 (19.4)12 (30.8)4 (18.2)8 (23.5)5 (20.0)16 (35.1)
      DM
      Yes20 (64.5)15 (38.5)0.03014 (63.6)13 (38.2)0.06315 (60.0)19 (42.2)0.154
      No11 (35.5)24 (61.5)8 (36.4)21 (61.8)10 (40.0)26 (57.8)

      Values are presented as numbers and percentages (%). LC: lung cancer, LUAD: lung adenocarcinoma, LUSC: lung squamous cell carcinoma, SCLC: small cell lung cancer, LM: lymphatic metastasis, DM: distant metastasis

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      Specific association of MTHFD1 expressions with small cell lung cancer development and chemoradiotherapy outcome
      Yujia Hao, Ruichun Lu, Ying Guo, Pengtao Bao
      Saudi Medical Journal Aug 2024, 45 (8) 783-790; DOI: 10.15537/smj.2024.45.8.20230990

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      Specific association of MTHFD1 expressions with small cell lung cancer development and chemoradiotherapy outcome
      Yujia Hao, Ruichun Lu, Ying Guo, Pengtao Bao
      Saudi Medical Journal Aug 2024, 45 (8) 783-790; DOI: 10.15537/smj.2024.45.8.20230990
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      Keywords

      • biomarker
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