Zhang W, Ye Y J, Ren X W, Huang J, Shen Z L
Department of Surgical Oncology, Peking University People's Hospital, Beijing 100044, China.
Department of Gastrointestinal Surgery, Peking University People's Hospital, Beijing 100044, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2019 Jun 18;51(3):542-547. doi: 10.19723/j.issn.1671-167X.2019.03.025.
To detect the preoperative chemoradiotherapy sensitivity molecular characteristics of rectal cancer by transcriptome second generation sequencing.
The clinicopathological data of 30 patients with locally advanced rectal cancer were collected prospectively, including 9 indicators (general conditions, imaging data before radiotherapy and chemotherapy, pathological data of biopsy before radiotherapy and chemotherapy, and tumor differentiation degree, etc.), in order to analyze the correlation between them and tumor regression grading (TRG) after radiotherapy and chemotherapy for rectal cancer. At the same time, frozen specimens of colonoscopy biopsy before neoadjuvant therapy were collected from these 30 patients, and transcriptome second-generation sequencing was performed for bioinformatics analysis to screen out the genes that might drive the radio chemotherapy sensitivity of rectal cancer.
Among the 30 patients with rectal cancer, 9 had complete pathological remission, 12 had partial remission, and 9 had poor remission. The degree of pathological TRG remission after radiotherapy and chemotherapy for rectal cancer was negatively correlated with the preoperative MRI T stage (P=0.046), and positively correlated with preoperative MRI rectal cancer extravascular invasion (EMVI) (P=0.003). Transcriptome second-generation sequencing of the obtained 217 transcripts (P<0.05) for signal pathway enrichment analysis, and multiple cell signal transduction pathways related to antigen presentation could be found. The high expression of HSPA1A, HSPA1B and EXOSC2 was positively correlated with postoperative pathological remission (P<0.05). The high expression of DNMBP, WASH8P, FAM57A, and SGSM2 was positively correlated with postoperative pathological remission (P<0.05).
Preoperative NMR detection of extra-tumoral vascular invasion (EMVI-positive) in patients with rectal cancer was significantly better than that of EMVI-negative patients after chemoradiotherapy. Patients with high expressions of HSPA1A, HSPA1B and EXOSC2 had poor postoperative pathological remission, while patients with high expressions of genes, such as DMNMB, WASH8P, FAM57A, and SGSM2 had good postoperative pathological remission. Based on the molecular characteristics of rectal cancer radiotherapy and chemotherapy, attempts to block or enhance the molecular pathways associated with chemosensitivity of rectal cancer, are to be made to further explore new candidate therapeutic targets that can increase the sensitivity of radiotherapy and chemotherapy for rectal cancer.
通过转录组二代测序检测直肠癌术前放化疗敏感性分子特征。
前瞻性收集30例局部晚期直肠癌患者的临床病理资料，包括9项指标（一般情况、放化疗前影像学资料、放化疗前活检病理资料、肿瘤分化程度等），分析其与直肠癌放化疗后肿瘤退缩分级（TRG）的相关性。同时，收集这30例患者新辅助治疗前结肠镜活检的冰冻标本，进行转录组二代测序及生物信息学分析，筛选出可能驱动直肠癌放化疗敏感性的基因。
30例直肠癌患者中，9例达到完全病理缓解，12例部分缓解，9例缓解较差。直肠癌放化疗后病理TRG缓解程度与术前MRI T分期呈负相关（P = 0.046），与术前MRI直肠癌血管外侵犯（EMVI）呈正相关（P = 0.003）。对获得的217条转录本进行转录组二代测序（P < 0.05）进行信号通路富集分析，可发现多条与抗原呈递相关的细胞信号转导通路。HSPA1A、HSPA1B及EXOSC2高表达与术后病理缓解呈正相关（P < 0.05）。DNMBP、WASH8P、FAM57A及SGSM2高表达与术后病理缓解呈正相关（P < 0.05）。
术前NMR检测直肠癌患者肿瘤外血管侵犯（EMVI阳性）者放化疗后明显优于EMVI阴性者。HSPA1A、HSPA1B及EXOSC2高表达患者术后病理缓解较差，而DMNMB、WASH8P、FAM57A及SGSM2等基因高表达患者术后病理缓解较好。基于直肠癌放化疗的分子特征，尝试阻断或增强与直肠癌化疗敏感性相关的分子通路，进一步探索可提高直肠癌放化疗敏感性的新候选治疗靶点。
