Changes in telomere length and mitochondrial DNA copy number in the colorectal adenoma-carcinoma sequence

Colorectal adenomas are anomalous growths of the intestinal epithelium and are considered precursors to colorectal cancer (CRC). Identifying early-stage CRC biomarkers is essential for reducing its high mortality rate. This study hypothesizes that the association of telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN) could serve as a biomarker for the adenoma or CRC formation. TL, mtDNA-CN, telomerase reverse transcriptase (TERT), and mitochondrial transcription factor A (TFAM) expressions were studied in 132 adenoma and 95 early-stage CRC patients. TL and mtDNA-CN were measured by multiplex quantitative polymerase chain reaction (qPCR). Expression of TERT and TFAM was measured by reverse transcription-qPCR. Significant TL shortening was observed in adenomas (P = 8.96e-14), tumor-node-metastasis (TNM) I (P = 3.49e-05), and TNM II (P = 2.29e-04) stages compared to the adjacent mucosa. This tendency was also contingent on TERT expression. Differential TFAM expression was observed in all groups, but an elevated relative mtDNA-CN was, compared to the adjacent mucosa, detected only in adenomas (P = 1.50e-08), where it correlated with TL (P = 4.10e-03). Notably, mtDNA-CN levels were significantly higher in adenomas than in early-stage tumors (TNM I, P = 2.00e-02; TNM II, P = 2.40e-02), suggesting a progressive decline during tumorigenesis. We have provided fresh insights into the crosstalk between telomere and mitochondrial biology in CRC precursors. These findings hold promise in understanding adenoma formation and CRC progression, as mtDNA-CN elevation and its association with TL were specific to precancerous lesions and were lost with progression to tumor.