Goossens-Beumer Inès J, Oosting Jan, Corver Wim E, Janssen Marjolein J F W, Janssen Bart, van Workum Wilbert, Zeestraten Eliane C M, van de Velde Cornelis J H, Morreau Hans, Kuppen Peter J K, van Wezel Tom
Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Department of Pathology, L1-Q, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands.
BMC Genomics. 2015 Jun 6;16(1):438. doi: 10.1186/s12864-015-1550-0.
In rectal cancer, total mesorectal excision surgery combined with preoperative (chemo)radiotherapy reduces local recurrence rates but does not improve overall patient survival, a result that may be due to the harmful side effects and/or co-morbidity of preoperative treatment. New biomarkers are needed to facilitate identification of rectal cancer patients at high risk for local recurrent disease. This would allow for preoperative (chemo)radiotherapy to be restricted to high-risk patients, thereby reducing overtreatment and allowing personalized treatment protocols. We analyzed genome-wide DNA copy number (CN) and allelic alterations in 112 tumors from preoperatively untreated rectal cancer patients. Sixty-six patients with local and/or distant recurrent disease were compared to matched controls without recurrence. Results were validated in a second cohort of tumors from 95 matched rectal cancer patients. Additionally, we performed a meta-analysis that included 42 studies reporting on CN alterations in colorectal cancer and compared results to our own data.
The genomic profiles in our study were comparable to other rectal cancer studies. Results of the meta-analysis supported the hypothesis that colon cancer and rectal cancer may be distinct disease entities. In our discovery patient study cohort, allelic retention of chromosome 7 was significantly associated with local recurrent disease. Data from the validation cohort were supportive, albeit not statistically significant, of this finding.
We showed that retention of heterozygosity on chromosome 7 may be associated with local recurrence in rectal cancer. Further research is warranted to elucidate the mechanisms and effect of retention of chromosome 7 on the development of local recurrent disease in rectal cancer.
在直肠癌中，全直肠系膜切除术联合术前（化疗）放疗可降低局部复发率，但并不能提高患者的总体生存率，这一结果可能归因于术前治疗的有害副作用和/或合并症。需要新的生物标志物来帮助识别局部复发性疾病高危的直肠癌患者。这将使术前（化疗）放疗仅限于高危患者，从而减少过度治疗并实现个性化治疗方案。我们分析了112例未经术前治疗的直肠癌患者肿瘤的全基因组DNA拷贝数（CN）和等位基因改变。将66例发生局部和/或远处复发性疾病的患者与未复发的匹配对照进行比较。结果在来自95例匹配直肠癌患者的第二批肿瘤队列中得到验证。此外，我们进行了一项荟萃分析，该分析纳入了42项报告结直肠癌CN改变的研究，并将结果与我们自己的数据进行比较。
我们研究中的基因组图谱与其他直肠癌研究相当。荟萃分析结果支持结肠癌和直肠癌可能是不同疾病实体的假设。在我们的发现患者研究队列中，7号染色体的等位基因保留与局部复发性疾病显著相关。验证队列的数据支持这一发现，尽管无统计学意义。
我们表明，7号染色体杂合性的保留可能与直肠癌的局部复发有关。有必要进一步研究以阐明7号染色体保留对直肠癌局部复发性疾病发展的机制和影响。
