scholarly journals Upregulated MUC2 Is an Unfavorable Prognostic Indicator for Rectal Cancer Patients Undergoing Preoperative CCRT

2021 ◽  
Vol 10 (14) ◽  
pp. 3030
Author(s):  
Chia-Lin Chou ◽  
Tzu-Ju Chen ◽  
Yu-Feng Tian ◽  
Ti-Chun Chan ◽  
Cheng-Fa Yeh ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Cancer Patients ◽  
Locally Advanced ◽  
Treatment Resistance ◽  
Radical Resection ◽  
Advanced Rectal Cancer ◽  
Prognostic Indicator ◽  
Locally Advanced Rectal Cancer ◽  
Free Survival ◽  
Muc2 Expression

For locally advanced rectal cancer patients, introducing neoadjuvant concurrent chemoradiotherapy (CCRT) before radical resection allows tumor downstaging and increases the rate of anus retention. Since accurate staging before surgery and sensitivity prediction to CCRT remain challenging, a more precise genetic biomarker is urgently needed to enhance the management of such situations. The epithelial mucous barrier can protect the gut lumen, but aberrant mucin synthesis may defend against drug penetration. In this study, we focused on genes related to maintenance of gastrointestinal epithelium (GO: 0030277) and identified mucin 2 (MUC2) as the most significantly upregulated gene correlated with CCRT resistance through a public rectal cancer transcriptome dataset (GSE35452). We retrieved 172 records of rectal cancer patients undergoing CCRT accompanied by radical resection from our biobank. We also assessed the expression level of MUC2 using immunohistochemistry. The results showed that upregulated MUC2 immunoexpression was considerably correlated with the pre-CCRT and post-CCRT positive nodal status (p = 0.001 and p < 0.001), advanced pre-CCRT and post-CCRT tumor status (p = 0.022 and p < 0.001), vascular invasion (p = 0.015), and no or little response to CCRT (p = 0.006). Upregulated MUC2 immunoexpression was adversely prognostic for all three endpoints, disease-specific survival (DSS), local recurrence-free survival (LRFS), and metastasis-free survival (MeFS) (all p < 0.0001), at the univariate level. Moreover, upregulated MUC2 immunoexpression was an independent prognostic factor for worse DSS (p < 0.001), LRFS (p = 0.008), and MeFS (p = 0.003) at the multivariate level. Collectively, these results imply that upregulated MUC2 expression is characterized by a more advanced clinical course and treatment resistance in rectal cancer patients undergoing CCRT, revealing the potential prognostic utility of MUC2 expression.

scholarly journals An Integrated Model of Pathological Complete Response and Postoperative CEA Predicts Survival and Benefit of Adjuvant Chemotherapy for Locally Advanced Rectal Cancer

2021 ◽  
Author(s):  
Shu-Biao Ye ◽  
Dong-Wen Chen ◽  
Pei-Si Li ◽  
Zhen-Sen Lin ◽  
Jia-Hui Long ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Cancer Patients ◽  
Pathological Complete Response ◽  
Locally Advanced ◽  
Biological Response ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Integrated Model ◽  
Free Survival

Abstract Background: Pathological complete response (pCR) and postoperative carcinoembryonic antigen (CEA) respectively represent pathological and biological response to treatment and prognostic indictors for locally advanced rectal cancer. However, the prognostic significance of integrated pCR and postoperative CEA model is rarely investigated. Methods: This big-data intelligence platform-based cohort biomarker study extracted clinicopathological characteristics and postoperative CEA of 919 locally advanced (clinical stage II-III) rectal cancer patients receiving neoadjuvant treatment from 6125 cases between April 2011 through September 2018 at Sun Yat-sen University, the Sixth Affiliated Hospital. An integrated model was constructed using pCR combined with the cut-off value of postoperative CEA generated from the receiver operating characteristic (ROC) curve. The model stratified locally advanced rectal cancer patients into four groups. Results: Both pathological response-pCR and biological response-postoperative CEA were independent prognostic indicators. In all patients, the 3-year distant metastasis-free survival (DMFS) (70.0%) and disease-free survival (DFS) (64.8%) rates were significantly lower in patients without pCR and postoperative CEA > 2.78 ng/ml (all p values < 0.05). Among patients treated with < 3 months of postoperative adjuvant chemotherapy (ACT), all others had higher 3-year DMFS and DFS rates. Among patients receiving ≥ 3 months of ACT, those without pCR had similar 3-year DMFS rates regardless of postoperative CEA level. Conclusions: The response integrated model with pCR and postoperative CEA not just effectively predict DMFS and DFS in locally advanced rectal cancer patients, but also was a predictive tool to potentially modify the optimal duration of ACT for locally advanced rectal cancer patients.

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