4.6 Article

Radiotranscriptomics signature-based predictive nomograms for radiotherapy response in patients with nonsmall cell lung cancer: Combination and association of CT features and serum miRNAs levels

Journal

CANCER MEDICINE
Volume 9, Issue 14, Pages 5065-5074

Publisher

WILEY
DOI: 10.1002/cam4.3115

Keywords

CT texture features; miRNAs; nomogram; nonsmall cell lung cancer; radiotherapy response

Categories

Funding

  1. Taishan Scholar Construction Project [ts20120505]
  2. National Key Research and Develop Program of China [2016YFC0105106]
  3. Key Research and Development Program of Shandong Province of China [2016GSF201123, 2017CXZC1206]
  4. National Natural Science Foundation of China [81530060, 81874224]
  5. Academic promotion program of Shandong First Medical University [2019LJ004]

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Purpose We aimed to establish radiotranscriptomics signatures based on serum miRNA levels and computed tomography (CT) texture features and develop nomogram models for predicting radiotherapy response in patients with nonsmall cell lung cancer (NSCLC). Methods We first used established radioresistant NSCLC cell lines for miRNA selection. At the same time, patients (103 for training set and 71 for validation set) with NSCLC were enrolled. Their pretreatment contrast-enhanced CT texture features were extracted and their serum miRNA levels were obtained. Then, radiotranscriptomics feature selection was implemented with the least absolute shrinkage and selection operator (LASSO), and signatures were generated by logistic or Cox regression for objective response rate (ORR), overall survival (OS), and progression-free survival (PFS). Afterward, radiotranscriptomics signature-based nomograms were constructed and assessed for clinical use. Results Four miRNAs and 22 reproducible contrast-enhanced CT features were used for radiotranscriptomics feature selection and we generated ORR-, OS-, and PFS- related radiotranscriptomics signatures. In patients with NSCLC who received radiotherapy, the radiotranscriptomics signatures were independently associated with ORR, OS, and PFS in both the training (OR: 2.94, P < .001; HR: 2.90, P < .001; HR: 3.58, P = .001) and validation set (OR: 2.94, P = .026; HR: 2.14, P = .004; HR: 2.64, P = .016). We also obtained a satisfactory nomogram for ORR. The C-index values for the ORR nomogram were 0.86 [95% confidence interval (CI), 0.75 to 0.92] in the training set and 0.81 (95% CI, 0.69 to 0.89) in the validation set. The calibration-in-the-large and calibration slope performed well. Decision curve analysis indicated a satisfactory net benefit. Conclusions The radiotranscriptomics signature could be an independent biomarker for evaluating radiotherapeutic responses in patients with NSCLC. The radiotranscriptomics signature-based nomogram could be used to predict patients' ORR, which would represent progress in individualized medicine.

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