Uncovering key molecular mechanisms in the early and late-stage of papillary thyroid carcinoma using association rule...

Thyroid Cancer (TC) is the most frequent endocrine malignancy neoplasm. It is the sixth cause of cancer in women worldwide. The treatment process could be expedited by identifying the controlling molecular mechanisms at the early and late stages, which can contribute to the acceleration of treatment schemes and the improvement of patient survival outcomes. In this work, we study the significant mRNAs through Machine Learning Algorithms in both the early and late stages of Papillary Thyroid Cancer (PTC).

During the course of our study, we investigated various methods and techniques to obtain suitable results. The sequence of procedures we followed included organizing data, using nested cross-validation, data cleaning, and normalization at the initial stage. Next, to apply feature selection, a t-test and binary Non-Dominated Sorting Genetic Algorithm II (NSGAII) were chosen to be employed. Later on, during the analysis stage, the discriminative power of the selected features was evaluated using machine learning and deep learning algorithms. Finally, we considered the selected features and utilized Association Rule Mining algorithm to identify the most important ones for improving the decoding of dominant molecular mechanisms in PTC through its early and late stages.

The SVM classifier was able to distinguish between early and late-stage categories with an accuracy of 83.5% and an AUC of 0.78 based on the identified mRNAs. The most significant genes associated with the early and late stages of PTC were identified as (e.g., ZNF518B, DTD2, CCAR1) and (e.g., lnc-DNAJB6-7:7, RP11-484D2.3, MSL3P1), respectively.

Current study reveals a clear picture of the potential candidate genes that could play a major role not only in the early stage, but also throughout the late one. Hence, the findings could be of help to identify therapeutic targets for more effective PTC drug developments.