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Performing Data Mining And Integrative Analysis Of Biomarker in Breast Cancer Using Multiple Publicly Accessible Databases
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Performing Data Mining And Integrative Analysis Of Biomarker in Breast Cancer Using Multiple Publicly Accessible Databases

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tRNA-Derived Fragments as Novel Predictive Biomarkers for Trastuzumab-Resistant Breast Cancer

Chunxiao Sun1,2, Fan Yang1,2, Yanhong Zhang1,2

  • 1Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
|August 29, 2018
PubMed
Abstract

Insights

Two tRNA-derived fragments, tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN, are linked to trastuzumab resistance in HER-2 positive breast cancer. Higher levels of these fragments indicate poorer response to trastuzumab therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Trastuzumab resistance is a significant obstacle in treating HER-2 positive breast cancer.
  • The mechanisms underlying trastuzumab resistance are not fully understood.
  • tRNA-derived small non-coding RNAs (sncRNAs) are emerging as key players in cancer progression.

Purpose of the Study:

  • To investigate the role of tRNA-derived fragments (tRFs) in trastuzumab resistance in HER-2 positive breast cancer.
  • To identify potential biomarkers for predicting response to trastuzumab therapy.

Main Methods:

  • High-throughput sequencing to detect tRF expression in breast cancer cell lines.
  • Quantitative reverse transcription PCR (qRT-PCR) to validate tRF levels in patient serum.
  • Receiver operating characteristic (ROC) curve analysis to assess diagnostic power.
  • Cox-regression analysis for progression-free survival (PFS).

Main Results:

  • tRFs were differentially expressed in trastuzumab-sensitive and -resistant cell lines.
  • tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN were significantly upregulated in trastuzumab-resistant patients.
  • ROC analysis confirmed the association of these tRFs with trastuzumab resistance.
  • Elevated levels of tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN correlated with shorter PFS in metastatic HER-2 positive breast cancer patients.

Conclusions:

  • tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN are implicated in trastuzumab resistance.
  • Patients with high expression of these tRFs may benefit less from trastuzumab treatment.
  • These tRFs show potential as biomarkers and therapeutic targets for trastuzumab-resistant breast cancer.
Keywords:
Breast cancerTrastuzumab resistancetRNA-derived fragments

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