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Journal of Peking University(Health Sciences) ›› 2019, Vol. 51 ›› Issue (3): 542-547. doi: 10.19723/j.issn.1671-167X.2019.03.025

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Detection of preoperative chemoradiotherapy sensitivity molecular characteristics of rectal cancer by transcriptome second generation sequencing

Wei ZHANG1,Ying-jiang YE2,Xian-wen REN3,Jing HUANG4,Zhan-long SHEN1△()   

  • Received:2019-03-25 Online:2019-06-18 Published:2019-06-26
  • Supported by:
    Supported by the Fundamental Research Funds for the Central Universities: Peking University Clinical Medicine Plus X-Young Scholars Project (PKU2018LCXQ021)

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Abstract: Objective: To detect the preoperative chemoradiotherapy sensitivity molecular characteristics of rectal cancer by transcriptome second generation sequencing.Methods: 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 can-cer. Results: 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).Conclusion: 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 characte-ristics 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.

Key words: Rectal neoplasms, Neoadjuvant therapy, Transcriptome sequencing, Tumor regression grading

CLC Number: 

  • R735.3

Table 1

Relationship between clinicopathological data and TRG classification in patients with colorectal cancer"

Clinical pathological data Number Complete remission Partial emission Non-remission P value
n % n % n %
Total 30 9 30.0 12 40.0 9 30.0
Gender 0.860
Male 23 6 26.1 10 43.5 7 30.4
Female 7 3 33.3 2 64.3 2 22.2
Age/years 0.732
<65 17 4 23.5 7 41.2 6 35.3
≥65 13 5 38.5 5 38.5 3 23.0
BMI >0.999
<18.5 1 0 0 1 100.0 0 0
18.5-23.9 11 4 36.4 4 36.4 3 27.2
≥24 18 5 27.8 7 38.9 6 33.3
MRI T staging 0.046
cT1 1 1 100.0 0 0 0 0
cT2 2 1 50.0 1 50.0 0 0
cT3 13 5 38.5 6 46.2 2 15.3
cT4 14 1 7.1 5 35.7 8 57.2
MRI N staging 0.926
cN0 16 5 31.3 6 37.5 5 31.3
cN+ 11 3 27.2 4 36.4 4 36.4
Undecided 3 1 33.3 2 66.7 0 0
EMVI 0.003
Positive 17 8 47.1 8 47.1 1 5.8
Negative 13 1 7.7 4 30.8 8 61.5
Tumormaximum diameter 0.898
>5 cm 11 3 27.2 4 36.4 4 36.4
≤5 cm 19 6 31.6 8 42.1 5 26.3
Pathological type 0.867
Adenocarcinoma 21 6 28.6 9 42.4 6 28.6
Mucinous adenocarcinoma 8 3 37.5 2 25.0 3 37.5
Signet ring cell carcinoma 1 0 0 1 100 0 0
Degree of differentiation 0.923
Low 6 1 16.7 3 50.0 2 33.3
Middle 11 3 27.2 5 45.5 3 27.2
High 13 5 38.5 4 30.7 4 30.7

Figure 1

Transcript expression associated with pathologic remission of preoperative chemoradiotherapy CR, complete remission group; PR, partial remission group; NR, non-remission group; TPM, transcripts per million."

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