Mesothelin Expression is Correlated with Chemoresistance in Stage IV Colorectal Cancer

• Published in: Annals of surgical oncology Vol. 28; no. 13; pp. 8579 - 8586
• Main Authors: Nagata, Ken, Shinto, Eiji, Shiraishi, Takehiro, Yamadera, Masato, Kajiwara, Yoshiki, Mochizuki, Satsuki, Okamoto, Koichi, Einama, Takahiro, Kishi, Yoji, Ueno, Hideki
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.12.2021; Springer Nature B.V
• Subjects: Biomarkers, Tumor; Cell surface; Chemoresistance; Chemotherapy; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Disease control; Drug Resistance, Neoplasm; GPI-Linked Proteins; Humans; Medical prognosis; Medicine; Medicine & Public Health; Mesothelin; Metastases; Oncology; Prognosis; Solid tumors; Surgery; Surgical Oncology; Translational Research
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-021-10507-y

Background Mesothelin (MSLN) is a cell-surface glycoprotein present on mesothelial cells; its expression in several epithelial cancers generally portends an unfavorable prognosis. We investigated MSLN as a surrogate chemopredictive biomarker and examined the impact of MSLN expression in stage IV colorectal cancer (CRC). Methods We recruited 254 patients with CRC who received systemic chemotherapy following primary tumor resection between 2000 and 2019. Resected specimens were immunostained for MSLN and stratified by MSLN expression. The associations of tumor MSLN expression with tumor response in metastatic lesions and survival were evaluated. Results Of the 247 patients with stage IV CRC, 41 (16.1%) and 213 (83.9%) had high and low MSLN expression, respectively. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, the investigator-assessed objective response rate was 22.0% in the high MSLN expression group and 45.5% in the low MSLN expression group ( p  = 0.0050). The disease control rates in these groups were 65.9% and 85.9%, respectively ( p  = 0.00019). In the patients with high MSLN expression, the conversion rate among those with initially unresectable metastases was 0% versus 14% in the patients with low MSLN expression ( p  = 0.0053). The median overall survival (OS) was 1.5 years (95% confidence interval [CI] 1.1–2.8) in the high MSLN expression group versus 2.6 years (95% CI 2.2–3.0) in the low MSLN expression group. The 3-year OS rates in these groups were 23.5 and 41.5%, respectively ( p  = 0.0120). Conclusions High MSLN expression is correlated with chemoresistance and poor prognoses in stage IV CRC.