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TEP linc-GTF2H2-1, RP3-466P17.2, and lnc-ST8SIA4-12 as novel biomarkers for lung cancer diagnosis and progression prediction

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Platelets contain a rich repertoire of RNA species, such as mRNAs and long non-coding RNAs. During the development of tumors, platelets are “educated” by cancer cells, altering their transcriptome and molecular content, thereby, tumor educated platelet (TEP) lncRNA profile has the potential to diagnose lung cancer. The current study was aimed to examine whether TEPs might be a potential biomarker for lung cancer.

Methods

Platelet precipitation was obtained by low-speed centrifugation. TEP linc-GTF2H2-1, RP3-466P17.2, and lnc-ST8SIA4-12 were selected by lncRNA microarray and validated by qPCR in a large cohort of lung cancer patients and healthy donors. Besides, we analyzed the association of their expression levels with clinicopathological features.

Results

TEP linc-GTF2H2-1 and RP3-466P17.2 were significantly downregulated, while lnc-ST8SIA4-12 was significantly upregulated in patients with lung cancer or with early-stage lung cancer as compared to healthy donors, possessing AUCs of 0.781, 0.788, 0.725 for lung cancer and 0.704, 0.771, 0.768 for early-stage lung cancer, respectively. Notably, their combination demonstrated the markedly elevated AUCs of 0.921 for lung cancer and 0.895 for early-stage lung cancer. Besides, the combination of TEP linc-GTF2H2-1 was capable to facilitate diagnostic efficiencies of CEA, Cyfra21-1, or NSE to distinguish advanced-stage lung cancer patients from early ones, with an AUC of 0.899 based on the integration of these four factors.

Conclusion

Our data suggested that lncRNAs sequestered in TEPs enabled blood-based lung cancer diagnosis and progression prediction.

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Availability of data and material

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

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Funding

This work was supported by the National Natural Science Foundation of China (81972014, 81672104, 8150111724), the Shandong Provincial Key Research and Development Program (2017CXGC1207, 2016GSF201146), Shandong Provincial Natural Science Foundation (ZR2019MH004 and ZR2019LZL016).

Author information

Authors and Affiliations

  1. Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 Ji-Yan Road, Jinan, 250117, Shandong Province, People’s Republic of China

    Xinyi Li, Lele Liu, Xingguo Song, Kangyu Wang, Limin Niu, Li Xie & Xianrang Song

  2. Department of Clinical Laboratory, Kunshan Hospital of Traditional Chinese Medicine, Kunshan, Jiangsu, People’s Republic of China

    Lele Liu

  3. Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China

    Xingguo Song & Xianrang Song

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  1. Xinyi Li
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  2. Lele Liu
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  4. Kangyu Wang
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  5. Limin Niu
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Contributions

XrS and XgS designed the experiments. XL and LL carried out the experiments. XL and XgS wrote the manuscript and prepared the figures. KW, LN and LX contributed to analysis the experimental data. All authors reviewed the manuscript and approved the final manuscript.

Corresponding author

Correspondence to Xianrang Song.

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The authors declare that there are no conflicts of interest.

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The studies involving human participants were reviewed and approved by Shandong Cancer Hospital Affiliated to Shandong First Medical University and Shandong Academy of Medical Sciences of Committee.

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Written informed consent to participate was obtained from all participants in this study.

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432_2020_3502_MOESM1_ESM.jpg

Figure S1: Platelet quality control. (A) Platelet purity was detected by Wright-Giemsa staining under a microscope; (B) Bioanalyzer graphs manifesting the quality of isolated platelet RNA associated with array samples; (C) Pearson correlation (color bar) matrix of publicly available datasets (columns and rows), consisting of five datasets with platelets (numbered 1-5, respectively), and one dataset containing seven different circulating immune cells (numbered 6), and the obtained microarray data in our study (highlighted in red). If applicable, the number of individuals per dataset was noted. The different platelet datasets were highly correlated, whereas no correlation was observed with circulating immune cells. PRP: platelet rich plasma; LC: lung cancer patients; HD: healthy donors; TEP: tumor educated platelets. (JPG 1626 KB)

432_2020_3502_MOESM2_ESM.jpg

Figure S2: GO analysis of target genes of TEP differential lncRNAs. (A) Over 250 target genes of TEP differential lncRNAs were involved in protein binding; (B) Cell adhesion and platelet activation were mainly involved in TEP lncRNA functions in lung cancer. (JPG 1483 KB)

432_2020_3502_MOESM3_ESM.jpg

Figure S3: Sanger sequencing performed on the PCR products of the three lncRNAs. PCR products of linc-GTF2H2-1 (A), RP3-466P17.2 (B) and lnc-ST8SIA4-12 (C) were verified pure and specific by Sanger sequencing. (JPG 2361 KB)

432_2020_3502_MOESM4_ESM.jpg

Figure S4: The differential levels of three blood markers between early-stage and advanced-stage lung cancer. The levels of CEA (A), Cyfra21-1 (B) and NSE (C) were increased in advanced-stage lung cancer patients compared with early-stage individuals. ****P<0.0001. (JPG 366 KB)

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Li, X., Liu, L., Song, X. et al. TEP linc-GTF2H2-1, RP3-466P17.2, and lnc-ST8SIA4-12 as novel biomarkers for lung cancer diagnosis and progression prediction. J Cancer Res Clin Oncol 147, 1609–1622 (2021). https://doi.org/10.1007/s00432-020-03502-5

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  • DOI: https://doi.org/10.1007/s00432-020-03502-5

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