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Peer-reviewedCC BY 4.0Oncology Research

A Key Biomarker lnc-ABCA12-5:2 Compensating Diagnostic Deficiencies for Indeterminate Thyroid Nodules and Genetically Wild-Type Thyroid Malignancies

  • Xuan Su1,2
  • Wen-na Xu1,3
  • Bu Zou1,2
  • Chan Huang4,5
  • Cai-yun He1,6
  • Zu-lu Ye1,6
6 affiliations
  1. 1State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
  2. 2Department of Head and Neck, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China
  3. 3Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China
  4. 4Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
  5. 5Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
  6. 6Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China
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Abstract

Background: Preoperative fine-needle aspiration (FNA) cytology and conventional genetic testing often fail on indeterminate thyroid nodules and malignancies lacking typical driver mutations. We validated two candidate lncRNAs, lnc-ABCA12-5:2 and lnc-MPEG1-1:1, initially screened in papillary thyroid carcinoma (PTC) tissues, using preoperative FNA and postoperative formalin-fixed paraffin-embedded (FFPE) specimens. Methods: Diagnostic performance was assessed in two independent cohorts encompassing diverse Bethesda categories and thyroid carcinoma subtypes. Molecular correlations and clinicopathological associations were also examined. Results: Both lncRNAs exhibited excellent diagnostic efficacy for PTC in preoperative FNA samples (area under the curve values: 0.923 and 0.968; sensitivity > 0.85; specificity > 0.90). lnc-ABCA12-5:2 achieved 100% specificity and 100% positive predictive value in Bethesda III–IV nodules, and was an independent predictor alongside BRAF V600E. Integrating lnc-ABCA12-5:2 with BRAF V600E testing raised diagnostic accuracy in indeterminate nodules from 89.5% to 95.0% (95.7% sensitivity, 92.9% specificity). lnc-ABCA12-5:2 positivity increased progressively with higher Bethesda grades (p-trend < 0.001), achieved 100% positivity in high-grade aggressive carcinomas, and remained elevated (83.6%) in genetically wild-type malignant nodules. Its expression strongly correlated with aggressive molecular signatures (including TERT, TP53, PI3K/AKT/PTEN alterations), yielding 100% positivity in such cases. In vitro cellular functional assays further confirmed that lnc-ABCA12-5:2 overexpression significantly promoted cell proliferation, colony formation, and migration in PTC cell lines. Conclusions: lnc-ABCA12-5:2 and lnc-MPEG1-1:1 are robust preoperative biomarkers for PTC. lnc-ABCA12-5:2 fills critical diagnostic gaps in indeterminate and genetically wild-type thyroid malignancies, and correlates with aggressive tumor molecular profiles, underscoring its translational potential for clinical risk stratification.

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Cite

BibTeXRIS
BibTeX
@article{su2026biomarker,
  title = {{A Key Biomarker lnc-ABCA12-5:2 Compensating Diagnostic Deficiencies for Indeterminate Thyroid Nodules and Genetically Wild-Type Thyroid Malignancies}},
  author = {Xuan Su and Wen-na Xu and Bu Zou and Chan Huang and Cai-yun He and Zu-lu Ye},
  journal = {Oncology Research},
  year = {2026},
  month = oct,
  doi = {10.32604/or.2026.088872},
  url = {https://doi.org/10.32604/or.2026.088872},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - A Key Biomarker lnc-ABCA12-5:2 Compensating Diagnostic Deficiencies for Indeterminate Thyroid Nodules and Genetically Wild-Type Thyroid Malignancies
AU  - Xuan Su
AU  - Wen-na Xu
AU  - Bu Zou
AU  - Chan Huang
AU  - Cai-yun He
AU  - Zu-lu Ye
PY  - 2026
DA  - 2026/10/28
JO  - Oncology Research
DO  - 10.32604/or.2026.088872
UR  - https://doi.org/10.32604/or.2026.088872
AB  - Background: Preoperative fine-needle aspiration (FNA) cytology and conventional genetic testing often fail on indeterminate thyroid nodules and malignancies lacking typical driver mutations. We validated two candidate lncRNAs, lnc-ABCA12-5:2 and lnc-MPEG1-1:1, initially screened in papillary thyroid carcinoma (PTC) tissues, using preoperative FNA and postoperative formalin-fixed paraffin-embedded (FFPE) specimens. Methods: Diagnostic performance was assessed in two independent cohorts encompassing diverse Bethesda categories and thyroid carcinoma subtypes. Molecular correlations and clinicopathological associations were also examined. Results: Both lncRNAs exhibited excellent diagnostic efficacy for PTC in preoperative FNA samples (area under the curve values: 0.923 and 0.968; sensitivity > 0.85; specificity > 0.90). lnc-ABCA12-5:2 achieved 100% specificity and 100% positive predictive value in Bethesda III–IV nodules, and was an independent predictor alongside BRAF V600E. Integrating lnc-ABCA12-5:2 with BRAF V600E testing raised diagnostic accuracy in indeterminate nodules from 89.5% to 95.0% (95.7% sensitivity, 92.9% specificity). lnc-ABCA12-5:2 positivity increased progressively with higher Bethesda grades (p-trend < 0.001), achieved 100% positivity in high-grade aggressive carcinomas, and remained elevated (83.6%) in genetically wild-type malignant nodules. Its expression strongly correlated with aggressive molecular signatures (including TERT, TP53, PI3K/AKT/PTEN alterations), yielding 100% positivity in such cases. In vitro cellular functional assays further confirmed that lnc-ABCA12-5:2 overexpression significantly promoted cell proliferation, colony formation, and migration in PTC cell lines. Conclusions: lnc-ABCA12-5:2 and lnc-MPEG1-1:1 are robust preoperative biomarkers for PTC. lnc-ABCA12-5:2 fills critical diagnostic gaps in indeterminate and genetically wild-type thyroid malignancies, and correlates with aggressive tumor molecular profiles, underscoring its translational potential for clinical risk stratification.
SN  - 0965-0407
SN  - 1555-3906
ER  -