Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 1-15 |
| Number of pages | 15 |
| Journal | JCO Precision Oncology |
| Volume | 2018 |
| Issue number | 2 |
| Early online date | 13 Jun 2018 |
| DOIs | |
| Publication status | Published - 2018 |
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Transcriptional subtyping and CD8 immunohistochemistry identifies poor prognosis stage II/III colorectal cancer patients who benefit from adjuvant chemotherapy. / Allen, W. L.; Dunne, P. D.; McDade, S.; Scanlon, E.; Loughrey, Maurice; Coleman, Helen; McCann, C.; McLaughlin, K.; Nemeth, Z.; Syed, N.; Jithesh, P.; Arthur, K.; Wilson, R.; Coyle, Vicky; McArt, Darragh; Murray, Graeme; Samuel, Leslie; Nuciforo, P.; Jimenez, J.; Argiles, G.; Dienstmann, R.; Tabernero, J.; Picariello, L.; Messerini, L.; Nobili, S.; Mini, E.; Sheahan, K.; Ryan, E.; Johnston, P. G. ; Van Schaeybroeck, S.; Lawler, Mark; Longley, D. B. .
In: JCO Precision Oncology, Vol. 2018, No. 2, 2018, p. 1-15.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Transcriptional subtyping and CD8 immunohistochemistry identifies poor prognosis stage II/III colorectal cancer patients who benefit from adjuvant chemotherapy
AU - Allen, W. L.
AU - Dunne, P. D.
AU - McDade, S.
AU - Scanlon, E.
AU - Loughrey, Maurice
AU - Coleman, Helen
AU - McCann, C.
AU - McLaughlin, K.
AU - Nemeth, Z.
AU - Syed, N.
AU - Jithesh, P.
AU - Arthur, K.
AU - Wilson, R.
AU - Coyle, Vicky
AU - McArt, Darragh
AU - Murray, Graeme
AU - Samuel, Leslie
AU - Nuciforo, P.
AU - Jimenez, J.
AU - Argiles, G.
AU - Dienstmann, R.
AU - Tabernero, J.
AU - Picariello, L.
AU - Messerini, L.
AU - Nobili, S.
AU - Mini, E.
AU - Sheahan, K.
AU - Ryan, E.
AU - Johnston, P. G.
AU - Van Schaeybroeck, S.
AU - Lawler, Mark
AU - Longley, D. B.
N1 - This work was funded by Cancer Research UK: C212/A13721 and C11884/A24387
PY - 2018
Y1 - 2018
N2 - Purpose: Transcriptomic profiling of colorectal cancer (CRC) has led to identification of four consensus molecular subtypes (CMS1-4), which have prognostic value in stage II/III disease. More recently, the Colorectal Cancer Intrinsic Subtypes (CRIS) classification system has helped to define the biology specific to the epithelial component of colorectal tumors. However, the clinical value of these classification systems in predicting response to standard of-care adjuvant chemotherapy remains unknown.Patients and Methods: Using samples from 4 European sites, we assembled a novel stage II/III CRC patient cohort (156 samples) and performed transcriptomic profiling, targeted sequencing and generated a tissue microarray to enable integrated “multi-omics” analyses. We also accessed data from 2 published stage II/III CRC patient cohorts: GSE39582 and GSE14333 (479 and 185 samples respectively).Results: The epithelial-rich CMS2 subtype of CRC benefitted significantly from adjuvant chemotherapy treatment in both stage II and III disease (p=0.02 and p<0.0001 respectively), while the CMS3 subtype significantly benefitted in stage III only (p=0.00073). Following CRIS sub-stratification of CMS2, we observed that only the CRIS-C subtype significantly benefitted from adjuvant chemotherapy in stage II and III disease (p=0.0081 and p<0.0001 respectively), while CRIS-D significantly benefitted in stage III only (p=0.0034). We also observed that CRIS-C patients with low levels of CD8+ tumor-infiltrating lymphocytes were most at risk of relapse in both stage II and III disease (log rank p=0.0031; Hazard ratio=12.18, 95%CI 1.51-98.58).Conclusion: Patient stratification using a combination of transcriptional subtyping and CD8 immunohistochemistry analyses is capable of identifying poor prognostic stage II/III patients who benefit from adjuvant standard-of-care chemotherapy. These findings are particularly relevant for stage II disease, where the overall benefit of adjuvant chemotherapy is marginal.
AB - Purpose: Transcriptomic profiling of colorectal cancer (CRC) has led to identification of four consensus molecular subtypes (CMS1-4), which have prognostic value in stage II/III disease. More recently, the Colorectal Cancer Intrinsic Subtypes (CRIS) classification system has helped to define the biology specific to the epithelial component of colorectal tumors. However, the clinical value of these classification systems in predicting response to standard of-care adjuvant chemotherapy remains unknown.Patients and Methods: Using samples from 4 European sites, we assembled a novel stage II/III CRC patient cohort (156 samples) and performed transcriptomic profiling, targeted sequencing and generated a tissue microarray to enable integrated “multi-omics” analyses. We also accessed data from 2 published stage II/III CRC patient cohorts: GSE39582 and GSE14333 (479 and 185 samples respectively).Results: The epithelial-rich CMS2 subtype of CRC benefitted significantly from adjuvant chemotherapy treatment in both stage II and III disease (p=0.02 and p<0.0001 respectively), while the CMS3 subtype significantly benefitted in stage III only (p=0.00073). Following CRIS sub-stratification of CMS2, we observed that only the CRIS-C subtype significantly benefitted from adjuvant chemotherapy in stage II and III disease (p=0.0081 and p<0.0001 respectively), while CRIS-D significantly benefitted in stage III only (p=0.0034). We also observed that CRIS-C patients with low levels of CD8+ tumor-infiltrating lymphocytes were most at risk of relapse in both stage II and III disease (log rank p=0.0031; Hazard ratio=12.18, 95%CI 1.51-98.58).Conclusion: Patient stratification using a combination of transcriptional subtyping and CD8 immunohistochemistry analyses is capable of identifying poor prognostic stage II/III patients who benefit from adjuvant standard-of-care chemotherapy. These findings are particularly relevant for stage II disease, where the overall benefit of adjuvant chemotherapy is marginal.
U2 - 10.1200/PO.17.00241
DO - 10.1200/PO.17.00241
M3 - Article
VL - 2018
SP - 1
EP - 15
JO - JCO Precision Oncology
JF - JCO Precision Oncology
SN - 2473-4284
IS - 2
ER -