Enhanced Clinical Utility of Molecular Budding Signature as a Recurrence Risk Determinant in Stage II and III Colon Cancer Patients

• Published in: Annals of surgical oncology Vol. 30; no. 8; pp. 5239 - 5247
• Main Authors: Shinto, Eiji, Oki, Eiji, Shimokawa, Mototsugu, Yamaguchi, Shigeki, Ishiguro, Megumi, Hasegawa, Seiji, Takii, Yasumasa, Ishida, Hideyuki, Kusumoto, Tetsuya, Morita, Masaru, Tomita, Naohiro, Shiozawa, Manabu, Tanaka, Masafumi, Ozawa, Heita, Hashiguchi, Yojiro, Ohnuma, Shinobu, Tada, Sachiyo, Matsushima, Tomoko, Yamagishi, Keisuke, Hase, Kazuo
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.08.2023; Springer Nature B.V
• Subjects: Cbfa-1 protein; Chemotherapy; Colon cancer; Colorectal cancer; Medicine; Medicine & Public Health; Oncology; Paraffin; Patients; Surgery; Surgical Oncology; Translational Research
• ISSN: 1068-9265; 1534-4681; 1534-4681
• DOI: 10.1245/s10434-023-13594-1

Background A molecular budding signature (MBS), which consists of seven tumor budding-related genes, was recently presented as a prominent prognostic indicator in colon cancer (CC) using microarray data acquired from frozen specimens. This study aimed to confirm the predictive power of MBS for recurrence risk based on formalin-fixed, paraffin-embedded (FFPE) materials. Methods This research utilized the same microarray data from a prior multicenter study using FFPE whole tissue sections, which retrospectively reviewed 232 stage II CC patients without adjuvant chemotherapy and 302 stage III CC patients with adjuvant chemotherapy. All patients underwent upfront curative surgery without neoadjuvant therapy between 2009 and 2012. An MBS score was calculated using the mean of log2 [each signal] of seven genes ( MSLN , SLC4A11 , WNT11 , SCEL , RUNX2 , MGAT3 , and FOXC1 ) as described before. Results The MBS-low group exhibited a better relapse-free survival (RFS) than the MBS-high group in stage II ( P  = 0.0077) and in stage III CC patients ( P  = 0.0003). Multivariate analyses revealed that the MBS score was an independent prognostic factor in both stage II ( P  = 0.0257) and stage III patients ( P  = 0.0022). Especially among T4, N2, or both (high-risk) stage III patients, the MBS-low group demonstrated markedly better RFS compared with the MBS-high group ( P  = 0.0013). Conclusions This study confirmed the predictive power of the MBS for recurrence risk by employing FFPE materials in stage II/III CC patients.