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Significance of mesothelin expression in preoperative endoscopic biopsy specimens for colorectal cancer prognosis.

ABSTRACT: Mesothelin (MSLN) is a cell surface glycoprotein that is normally expressed in the mesothelial cells but highly expressed in several malignant tumors, where the high expression is generally associated with poor prognosis. In this work, 512 patients with stage III colorectal cancer (CRC) were examined to ascertain the prognostic value of MSLN expression in preoperative endoscopic biopsy specimens. MSLN expression was evaluated by immunohistochemical staining. The tumor cells were MSLN-positive in 61 of the 512 patients (11.9%). MSLN expression was associated with a shorter disease-specific survival (DSS) period (5-year DSS = 68.7%, P = 0.0008). Besides, by multivariate analysis, MSLN expression was identified to be a marker of poor prognosis by multivariate analysis (P = 0.0033, hazard ratio (HR) = 2.31) as well as macroscopic type (P = 0.047, HR = 1.82) among the factors that can be evaluated preoperatively. MSLN-positive patients had a significantly poorer prognosis regardless of adjuvant chemotherapy administration (P = 0.0081 and P = 0.0018 for surgery alone and chemotherapy, respectively). MSLN-positive patients in the adjuvant chemotherapy group exhibited a significantly lower risk of recurrence when compared with those in the surgery alone group (P = 0.0090). In conclusion, high MSLN expression observed in preoperative endoscopic biopsy specimens of stage III CRC was an independent poor prognostic factor. Preoperative evaluation of MSLN by immunohistochemical staining might be applied to select individuals for intensive preoperative chemotherapy among the stage III CRC patients.

SUBMITTER: Shiraishi T

PROVIDER: S-EPMC7597413 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Significance of mesothelin expression in preoperative endoscopic biopsy specimens for colorectal cancer prognosis.

Shiraishi Takehiro T Shinto Eiji E Yamadera Masato M Nagata Ken K Tsuda Hitoshi H Mochizuki Satsuki S Kajiwara Yoshiki Y Okamoto Koichi K Einama Takahiro T Kishi Yoji Y Ueno Hideki H

Oncotarget 20201027 43

Mesothelin (MSLN) is a cell surface glycoprotein that is normally expressed in the mesothelial cells but highly expressed in several malignant tumors, where the high expression is generally associated with poor prognosis. In this work, 512 patients with stage III colorectal cancer (CRC) were examined to ascertain the prognostic value of MSLN expression in preoperative endoscopic biopsy specimens. MSLN expression was evaluated by immunohistochemical staining. The tumor cells were MSLN-positive in ...[more]

PMID: 33196692

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Project description:ObjectiveThe aim of this study is to explore the consistency of P53 immunohistochemical expression between preoperative biopsy and final pathology in endometrial cancer (EC), and to predict the prognosis of patients based on the 4-tier P53 expression and classic clinicopathological parameters.MethodsThe medical data of patients with stage I-III EC who received preoperative biopsy and initial surgical treatment in two medical centers was retrospectively collected. The consistency of P53 immunohistochemistry expression between preoperative biopsy and final pathology was compared using Cohen's kappa coefficient and Sankey diagram, then 4-tier P53 expression was defined (P53wt/P53wt, P53abn/P53wt, P53wt/P53abn, and P53abn/P53abn). Univariate and multivariate Cox regression analysis was used to determine the correlation between 4-tier P53 expression and the prognosis of patients. On this basis, the nomogram models were established to predict the prognosis of patients by combining 4-layer P53 expression and classic clinicopathological parameters, then risk stratification was performed on patients.ResultsA total of 1186 patients were ultimately included in this study through inclusion and exclusion criteria. Overall, the consistency of P53 expression between preoperative biopsy and final pathology was 83.8%, with a kappa coefficient of 0.624. ROC curve suggested that the AUC of 4-tier P53 expression to predict the prognosis of patients was better than AUC of P53 expression in preoperative biopsy or final pathology alone. Univariate and multivariate Cox regression analysis suggested that 4-tier P53 expression was an independent influencing factor for recurrence and death. On this basis, the nomogram models based on 4-tier P53 expression and classical clinicopathological factors were successfully established. ROC curve suggested that the AUC (AUC for recurrence and death was 0.856 and 0.838, respectively) of the models was superior to the single 4-tier P53 expression or the single classical clinicopathological parameters, which could provide a better risk stratification for patients.ConclusionThe expression of P53 immunohistochemistry had relatively good consistency between preoperative biopsy and final pathology of EC. Due to the discrepancy of P53 immunohistochemistry between preoperative biopsy and final pathology, the prognosis of patients can be better evaluated based on the 4-layer P53 expression and classic clinical pathological parameters.

Project description:Rationale: Cancer phosphoproteomics can provide insights regarding kinases that can be targeted for therapeutic applications. Monitoring the phosphoproteomics in cancer is expected to play a key role in optimizing treatments with kinase inhibitors. Clinical phosphoproteomics in surgical tissues and patient-derived models has been studied intensively. However, the reported data may not accurately reflect the phosphosignaling status in patients due to the effect of ischemia occurring during surgery or changes in the characteristics of cancer cells when establishing the models. In contrast, endoscopic biopsies have an advantage for clinical phosphoproteomics because they can be rapidly cryo-preserved. We aimed to develop a highly sensitive method for phosphoproteomics in endoscopic biopsies of gastric cancer. Methods: Three tumor biopsies and three normal gastric biopsies were obtained by endoscopy at one time, and subjected to our optimized phosphoproteomics. Phosphopeptides were enriched with an immobilized metal affinity chromatography, and labeled with Tandem Mass Tag reagent. Quantified phosphosites were compared between the pairs of tumor/normal biopsies within same patient. Cancer-specific activated pathways and kinases were identified by pathway enrichment analysis and kinase-substrate enrichment analysis. Results: Our protocol enabled the identification of more than 10,000 class 1 phosphosites from endoscopic biopsies. A comparison between samples from cancer tissue and normal mucosa demonstrated differences in the phosphosignaling, including biomarkers of response to DNA damage. Finally, cancer-specific activation of DNA damage response signaling was validated by additional phosphoproteomics of other patients and western blotting of gastric cancer/normal cells. Conclusion: In summary, our pioneering approach will facilitate more accurate clinical phosphoproteomics in endoscopic biopsies, which can be applied to monitor the activities of therapeutic kinases and, ultimately, can be a useful tool to precision medicine.

Dataset Information

Significance of mesothelin expression in preoperative endoscopic biopsy specimens for colorectal cancer prognosis.

Publications

Significance of mesothelin expression in preoperative endoscopic biopsy specimens for colorectal cancer prognosis.

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