TY - JOUR
T1 - Young-onset Rectal Cancer
T2 - Unique Tumoral Microbiome and Correlation With Response to Neoadjuvant Therapy
AU - White, Michael G.
AU - Damania, Ashish
AU - Alshenaifi, Jumanah
AU - Sahasrabhojane, Pranoti
AU - Peacock, Oliver
AU - Losh, Jillian
AU - Wong, Matthew C.
AU - Lutter-Berkova, Zuzana
AU - Chang, George J.
AU - Futreal, Andrew
AU - Wargo, Jennifer A.
AU - Ajami, Nadim J.
AU - Kopetz, Scott
AU - You, Y. Nancy
N1 - Publisher Copyright:
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2023/10/1
Y1 - 2023/10/1
N2 - Objective: External exposures, the host, and the microbiome interact in oncology. We aimed to investigate tumoral microbiomes in young-onset rectal cancers (YORCs) for profiles potentially correlative with disease etiology and biology. Background: YORC is rapidly increasing, with 1 in 4 new rectal cancer cases occurring under the age of 50 years. Its etiology is unknown. Methods: YORC (<50 y old) or later-onset rectal cancer (LORC, ≥50 y old) patients underwent pretreatment biopsied of tumor and tumor-adjacent normal (TAN) tissue. After whole genome sequencing, metagenomic analysis quantified microbial communities comparing tumors versus TANs and YORCs versus LORCs, controlling for multiple testing. Response to neoadjuvant therapy (NT) was categorized as major pathological response (MPR, ≤10% residual viable tumor) versus non-MPR. Results: Our 107 tumors, 75 TANs from 37 (35%) YORCs, and 70 (65%) LORCs recapitulated bacterial species were previously associated with colorectal cancers (all P<0.0001). YORC and LORC tumoral microbiome signatures were distinct. After NT, 13 patients (12.4%) achieved complete pathologic response, whereas MPR occurred in 47 patients (44%). Among YORCs, MPR was associated with Fusobacterium nucleaum, Bacteroides dorei, and Ruminococcus bromii (all P<0.001), but MPR in LORC was associated with R. bromii (P<0.001). Network analysis of non-MPR tumors demonstrated a preponderance of oral bacteria not observed in MPR tumors. Conclusions: Microbial signatures were distinct between YORC and LORC. Failure to achieve an MPR was associated with oral bacteria in tumors. These findings urge further studies to decipher correlative versus mechanistic associations but suggest a potential for microbial modulation to augment current treatments.
AB - Objective: External exposures, the host, and the microbiome interact in oncology. We aimed to investigate tumoral microbiomes in young-onset rectal cancers (YORCs) for profiles potentially correlative with disease etiology and biology. Background: YORC is rapidly increasing, with 1 in 4 new rectal cancer cases occurring under the age of 50 years. Its etiology is unknown. Methods: YORC (<50 y old) or later-onset rectal cancer (LORC, ≥50 y old) patients underwent pretreatment biopsied of tumor and tumor-adjacent normal (TAN) tissue. After whole genome sequencing, metagenomic analysis quantified microbial communities comparing tumors versus TANs and YORCs versus LORCs, controlling for multiple testing. Response to neoadjuvant therapy (NT) was categorized as major pathological response (MPR, ≤10% residual viable tumor) versus non-MPR. Results: Our 107 tumors, 75 TANs from 37 (35%) YORCs, and 70 (65%) LORCs recapitulated bacterial species were previously associated with colorectal cancers (all P<0.0001). YORC and LORC tumoral microbiome signatures were distinct. After NT, 13 patients (12.4%) achieved complete pathologic response, whereas MPR occurred in 47 patients (44%). Among YORCs, MPR was associated with Fusobacterium nucleaum, Bacteroides dorei, and Ruminococcus bromii (all P<0.001), but MPR in LORC was associated with R. bromii (P<0.001). Network analysis of non-MPR tumors demonstrated a preponderance of oral bacteria not observed in MPR tumors. Conclusions: Microbial signatures were distinct between YORC and LORC. Failure to achieve an MPR was associated with oral bacteria in tumors. These findings urge further studies to decipher correlative versus mechanistic associations but suggest a potential for microbial modulation to augment current treatments.
KW - colorectal cancer
KW - microbiome
KW - neoadjuvant therapy
KW - rectal cancer
KW - young-onset rectal cancers
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U2 - 10.1097/SLA.0000000000006015
DO - 10.1097/SLA.0000000000006015
M3 - Article
C2 - 37465976
AN - SCOPUS:85170295344
SN - 0003-4932
VL - 278
SP - 538
EP - 548
JO - Annals of surgery
JF - Annals of surgery
IS - 4
ER -