Mzahma Raja, Kharrat Maher, Fetiriche Fadhel, Ben Moussa Mounir, Ben Safta Zoubeir, Dziri Chadli, Zaouche AbdelJelil, Chaabouni-Bouhamed Habiba
Human Genetics Laboratory, Faculty of Medicine of Tunis, 15 rue Djebel Lakdhar La Rabta, Tunis, 1007, Tunisia.
Department of General Surgery A, La Rabta Hospital, Tunis, 1007, Tunisia.
Tumour Biol. 2015 Nov;36(11):8703-13. doi: 10.1007/s13277-015-3545-5. Epub 2015 Jun 6.
Alterations in telomere dynamics have emerged as having a causative role in carcinogenesis. Both the telomere attrition contribute to tumor initiation via increasing chromosomal instability and that the telomere elongation induces cell immortalization and leads to tumor progression. The objectives of this study are to investigate the dynamics of telomere length in colorectal cancer (CRC) and the clinicopathological parameters implicated. We measured the relative telomere length (RTL) in cancerous tissues and in corresponding peripheral blood leukocytes (PBL) using quantitative PCR (Q-PCR) from 94 patients with CRC. Telomere length correlated significantly in cancer tissues and corresponding PBL (r = 0.705). Overall, cancer tissue had shorter telomeres than PBL (p = 0.033). In both cancer tissue and PBL, the RTL was significantly correlated with age groups (p = 0.008 and p = 0.012, respectively). The RTL in cancer tissue was significantly longer in rectal tumors (p = 0.04) and in the late stage of tumors (p = 0.01). In PBL, the RTL was significantly correlated with the macroscopic aspect of tumors (p = 0.02). In addition, the telomere-length ratio of cancer to corresponding PBL increased significantly with late-stage groups. Shortening of the telomere was detected in 44.7%, elongation in 36.2%, and telomeres were unchanged in 19.1% of 94 tumors. Telomere shortening occurred more frequently in the early stage of tumors (p = 0.01). This study suggests that the telomere length in PBL is affected by the macroscopic aspect of tumors and that telomere length in cancer tissues is a marker for progression of CRC and depends on tumor-origin site.
端粒动态变化已被证明在癌症发生过程中具有致病作用。端粒磨损通过增加染色体不稳定性促进肿瘤起始，而端粒延长则诱导细胞永生化并导致肿瘤进展。本研究的目的是调查结直肠癌（CRC）中端粒长度的动态变化以及相关的临床病理参数。我们使用定量PCR（Q-PCR）对94例CRC患者的癌组织和相应的外周血白细胞（PBL）中的相对端粒长度（RTL）进行了测量。癌组织和相应的PBL中的端粒长度显著相关（r = 0.705）。总体而言，癌组织的端粒比PBL短（p = 0.033）。在癌组织和PBL中，RTL均与年龄组显著相关（分别为p = 0.008和p = 0.012）。癌组织中的RTL在直肠肿瘤中显著更长（p = 0.04），在肿瘤晚期也显著更长（p = 0.01）。在PBL中，RTL与肿瘤的大体形态显著相关（p = 0.02）。此外，癌组织与相应PBL的端粒长度比随分期增加而显著升高。在94个肿瘤中，44.7%检测到端粒缩短，36.2%检测到端粒延长，19.1%的端粒无变化。端粒缩短在肿瘤早期更频繁发生（p = 0.01）。本研究表明，PBL中的端粒长度受肿瘤大体形态影响，癌组织中的端粒长度是CRC进展的标志物，且取决于肿瘤起源部位。
