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Evaluation of GREM1 and THBS2 as prognostic markers in in non-small cell lung cancer

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Abstract

Objective

To analyze the correlation between bone morphogenetic protein (BMP) antagonist Gremlin 1 (GREM1), Thrombospondin-2 (THBS2) and immune cell infiltration in non-small cell lung cancer (NSCLC) and the related clinical significance.

Methods

A total of 150 NSCLC patients admitted to our hospital during May 2019–January 2022 were picked. The expression of GREM1 and THBS2 and the infiltration of immune cells in tumor tissues were detected through immunohistochemistry (IHC). These objects were graded as GREM1-positive group (n = 97), GREM1-negative group (n = 53), THBS2-positive group (n = 102) and THBS2-negative group (n = 48) according to the expression of GREM1 and THBS2. The correlation between the expression of GREM1 and THBS2 with immune cell infiltration and clinicopathological indicators was analyzed. Kaplan–Meier survival analysis was adopted to analyze the relationship between the expression of GREM1 and THBS2 and the prognosis in NSCLC tissues. The overall progression-free survival (PFS) of the two groups were compared by log-rank test.

Results

The results of IHC showed that the positive expression rate of GREM1 was 64.67% (97/150) in cancer tissues and 36.00% (54/150) in adjacent tissues. The positive expression rate of THBS2 was 68.00% (102/150) in cancer tissues and 25.33% (38/150) in adjacent tissues. The positive expression rate of GREM1 and THBS2 in cancer tissues was both much higher than that in adjacent tissues (P < 0.01). GREM1-positive group had much higher proportion of tumor diameter ≥ 2 cm, stage III–IV and lymph-node metastasis than GREM1-negative group (P < 0.05). THBS2-positive group had markedly higher proportion of tumor diameter ≥ 2 cm, stage III–IV, lymph-node metastasis and high differentiation than THBS2-negative group (P < 0.01). GREM1-positive group had much higher level of CD3 + T, and sharply lower level of CD8 + T and CD11c + DCs than GREM1-negative group (P < 0.01). THBS2-positive group had much higher level of CD3 + T, and sharply lower level of CD8 + T and CD11c + DCs than THBS2-negative group (P < 0.01). According to Kaplan–Meier survival analysis, the overall median progression-free survival (PFS) was 7.45 months. Log-rank test showed that NSCLC patients with positive GREM1 and THBS2 had much shorter PFS than negative patients (P < 0.01). Log-rank test showed that the expression of GREM1 and THBS2 was related to the PFS of patients (P < 0.01).

Conclusion

GREM1 and THBS2 were highly expressed in NSCLC tissues and acted as pro-oncogenes in the development and progression of NSCLC, which aggravated the disease by mediating immune cell infiltration.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

No external funding received to conduct this study.

Author information

Author notes

  1. Yufang Bao and Ershuai Yan have contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine, Huanghe S & T University, No. 666, Zijingshan South Road, Zhengzhou, 450000, Henan Province, People’s Republic of China

    Yufang Bao

  2. Department of Thoracic Surgery, The First Affiliated Hospital of XinXiang Medical University, No. 88, Jian Kang Road, Weihui City, 453100, Henan Province, People’s Republic of China

    Yufang Bao & Ershuai Yan

  3. Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China

    Na Wang

  4. Institutes of Integrative Medicine, Fudan University, Shanghai, 200433, People’s Republic of China

    Na Wang

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  1. Yufang Bao
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  2. Ershuai Yan
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  3. Na Wang
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Contributions

YFB and ESY conceived the idea and conceptualised the study. YFB and ESY collected the data. ESY and NW analysed the data. YFB and NW drafted the manuscript, then NW reviewed the manuscript. All authors read and approved the final draft.

Corresponding author

Correspondence to Na Wang.

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The authors declare that they have no competing interests.

Ethical approval and consent to participate

This study was conducted with approval from the Ethics Committee of our hospital. This study was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participants.

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Bao, Y., Yan, E. & Wang, N. Evaluation of GREM1 and THBS2 as prognostic markers in in non-small cell lung cancer. J Cancer Res Clin Oncol 149, 7849–7856 (2023). https://doi.org/10.1007/s00432-023-04746-7

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  • DOI: https://doi.org/10.1007/s00432-023-04746-7

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