Abstract
Background
This study was designed to detect patients with early NSCLC with tentatively using the stem signatures associated autoantibodies (AAbs), and to evaluate its latent values in the early diagnosis and precise prognosis prediction.
Methods
The serum concentrations of selective antibodies were quantitated by enzyme-linked immunosorbent assay (ELISA), and a total of 458 cases were enrolled (training set = 401; validation set = 57). TCGA databases were used to analyze the distinct expressions and prognostic values of related genes. The optimal cut-off values were 11.60 U/ml for P53, 4.90 U/ml for MAGEA1, 3.85 U/ml for SOX2, and 7.05U/ml for PGP9.5.
Results
We found that the stem signatures associated antibodies of MAGEA1, PGP9.5, SOX2, and TP53 exhibited high expressions in NSCLC, negatively correlating with the overall survival (OS) (P < 0.05). In the test groups, the diagnosis sensitivity of P53, PGP9.5, SOX2, and MAGEA1 reached to 21.5%, 39.0%, 50.3%, and 35.0%, respectively, and the specificity reached to 98.7%, 99.4%, 92.2%, and 97.4%. The four candidates’ panel gave a sensitivity of 71.8% with a specificity of 89%. In the validation group, the detection of the four antibodies in early diagnosis of NSCLC also exhibited high specificity and sensitivity, further consolidating their potential application.
Conclusions
The detection regarding stem signatures associated antibodies could be used as effective tools in early NSCLC diagnosis, but not for localized screening of cancers, and their abnormal expression was in accordance with poorer survival.
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Acknowledgements
The authors acknowledge assistants in the Center for Translational Medicine of First Affiliated Hospital of Xi’an Jiaotong University, for their technical assistance. The authors are very appreciative of the great help they received from the staffs of the Thoracic Department and Oncology Department. This experiment was supported by the National Science Foundation for Young Scientists of China, grant No. 81602597 (Referred to Xin Sun), and Foundation Research Project of Shaanxi Province (The Natural Science Fund No. 2018JM7017 (Referred to Xin Sun).
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432_2020_3325_MOESM1_ESM.tif
Figure S1 Expression patterns of Stem signatures associated antibodiesThe stem cells potency associated UCHL1, SOX2, TP53, MAGEA1, SOX4, WNT1, TCF4, NOTCH1, KLF4, MYC, LIN28A, LIN28B, SNAI1, PROM1, ALDH1A1, CD44, CREBBP, were all applied for expression, and the results were exhibited in heatmap. Detections regarding to stem cells potency associated members were universally deregulated, enhanced with mutated or overexpressed status
432_2020_3325_MOESM2_ESM.tif
Figure S2 Protein expression patterns of Stem signatures associated antibodies A. Strong cytoplasmic staining of PGP9.5 was found in cases of gliomas, malignant, testis, cervical and lung cancers. The positivity was often accompanied with weak to moderate nuclear immunoreactivity. B. Strong nuclear positivity of SOX2 was mainly observed in several cases of glioma, testis cancer and squamous cell carcinoma. C. Many malignant cells displayed moderate to strong nuclear positivity of TP53. D. Moderate to string cytoplasmic and nuclear immunoreactivity of MAGEA1 was observed in a few cases of testicular, skin, lung and head & neck cancers. Remaining malignant cells were generally negative
432_2020_3325_MOESM3_ESM.tif
Figure S3 The expressions of four Stem signatures associated genes in multiple malignanciesThe graph shows the number of analyses meeting the threshold with statistically significant over-expression (red) or down-regulated expression (blue) of the target gene. Cell color is determined by the best gene rank percentile for the analyses within the cell. (A) MAGEA1, (B) PGP9.5, (C) SOX2, (D) TP53 expressions associated genes in multiple malignancies
432_2020_3325_MOESM4_ESM.tif
Figure S4 Expressions of four genes in LUAD and LUSC Box plots were used to compare the distinct expressions of MAGEA1 (A), PGP9.5 (B), SOX2 (C) and TP53 (D), either between LUSC and normal tissues, or between LUAD and normal tissues, by analyzing the GEPIA database. The threshold was set as Log2FC=1, p = 0.05. T was tumor. N was normal. * P value <0.05.
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Chen, SS., Li, K., Wu, J. et al. Stem signatures associated antibodies yield early diagnosis and precise prognosis predication of patients with non-small cell lung cancer. J Cancer Res Clin Oncol 147, 223–233 (2021). https://doi.org/10.1007/s00432-020-03325-4
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DOI: https://doi.org/10.1007/s00432-020-03325-4