Expression of long non‑coding RNAs DIAPH3‑AS1, HMMR‑AS1, and SPATA3‑AS1 in patients with colorectal cancer: association with chemotherapy response and clinicopathological features.
Antisense long non-coding RNAs (lncRNAs) may fine-tune expression of their overlapping sense genes in cancer. DIAPH3-AS1, HMMR-AS1, and SPATA3-AS1 remain uncharacterized in colorectal cancer (CRC), and SPATA3-AS1 has not been studied in any malignancy.
Ninety CRC patients were enrolled, with paired tumor biopsies collected before and after capecitabine-based chemotherapy; 71 healthy individuals served as controls. Expression of the three lncRNAs was measured by qRT-PCR and normalized to β-actin (2 - ΔCt method). Group and paired comparisons used the Mann-Whitney U and Wilcoxon signed-rank tests, and diagnostic value was assessed by ROC analysis. All three lncRNAs were significantly overexpressed in pre-treatment CRC tissue versus healthy mucosa (fold-changes 2.22-2.87; p < 0.001). After chemotherapy, HMMR-AS1 fell significantly (1.60-fold, p = 0.0012), becoming indistinguishable from controls (p = 0.133), whereas DIAPH3-AS1 and SPATA3-AS1 remained elevated. HMMR-AS1 was also higher in well/moderately differentiated than poorly differentiated tumors (p = 0.0067); none of the three transcripts was associated with TNM stage, lymph node metastasis, tumor site, or treatment response. ROC analysis showed modest baseline discrimination (AUC 0.652-0.699), and HMMR-AS1's diagnostic performance declined after treatment (AUC 0.569), consistent with its chemo-responsiveness.
DIAPH3-AS1, HMMR-AS1, and SPATA3-AS1 are consistently upregulated in CRC tissue at diagnosis, but only HMMR-AS1 is sensitive to chemotherapy and differentiation grade, indicating transcript-specific roles for antisense lncRNAs in CRC biology.
Ninety CRC patients were enrolled, with paired tumor biopsies collected before and after capecitabine-based chemotherapy; 71 healthy individuals served as controls. Expression of the three lncRNAs was measured by qRT-PCR and normalized to β-actin (2 - ΔCt method). Group and paired comparisons used the Mann-Whitney U and Wilcoxon signed-rank tests, and diagnostic value was assessed by ROC analysis. All three lncRNAs were significantly overexpressed in pre-treatment CRC tissue versus healthy mucosa (fold-changes 2.22-2.87; p < 0.001). After chemotherapy, HMMR-AS1 fell significantly (1.60-fold, p = 0.0012), becoming indistinguishable from controls (p = 0.133), whereas DIAPH3-AS1 and SPATA3-AS1 remained elevated. HMMR-AS1 was also higher in well/moderately differentiated than poorly differentiated tumors (p = 0.0067); none of the three transcripts was associated with TNM stage, lymph node metastasis, tumor site, or treatment response. ROC analysis showed modest baseline discrimination (AUC 0.652-0.699), and HMMR-AS1's diagnostic performance declined after treatment (AUC 0.569), consistent with its chemo-responsiveness.
DIAPH3-AS1, HMMR-AS1, and SPATA3-AS1 are consistently upregulated in CRC tissue at diagnosis, but only HMMR-AS1 is sensitive to chemotherapy and differentiation grade, indicating transcript-specific roles for antisense lncRNAs in CRC biology.
Authors
Houshmand Houshmand, Safaralizadeh Safaralizadeh, Khalaj-Kondori Khalaj-Kondori
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