Management of Non-Colorectal Digestive Cancers with Microsatellite Instability

Zhu, Mojun; Jin, Zhaohui; Hubbard, Joleen M.

doi:10.3390/cancers13040651

Cited by 11 publications

(8 citation statements)

References 172 publications

(237 reference statements)

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“…Immune checkpoint inhibitors (ICIs), which represent a new method for developing immunotherapies, have become a potential weapon in fighting different cancers [33]. The TMB and MSI are predictive biomarkers in patients with tumors receiving immunotherapy [34][35][36]. Patients with a high TMB or MSI are more likely to experience a long-term survival benefit from immunotherapy [37,38].…”

Section: Discussionmentioning

confidence: 99%

METTL7B is a novel prognostic biomarker of lower-grade glioma based on pan-cancer analysis

Jiang

Zhu³

et al. 2021

Cancer Cell Int

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Methyltransferase-like 7B (METTL7B) is a member of the methyltransferase-like protein family that plays an important role in the development and progression of tumors. However, its prognostic value and the correlation of METTL7B expression and tumor immunity in some cancers remain unclear. By analyzing online data, we found that METTL7B is abnormally overexpressed in multiple human tumors and plays an important role in the overall survival (OS) of patients with 8 cancer types and disease-free survival (DFS) of patients with 5 cancer types. Remarkably, METTL7B expression was positively correlated with the OS and DFS of patients with lower-grade glioma (LGG). In addition, a positive correlation between METTL7B expression and immune cell infiltration in LGG was observed. Moreover, we identified a strong correlation between METTL7B expression and immune checkpoint gene expression in kidney chromophobe (KICH), LGG and pheochromocytoma and paraganglioma (PCPG). Furthermore, METTL7B was involved in the extracellular matrix (ECM) and immune-related pathways in LGGs. Finally, in vitro experiments showed that knockdown of METTL7B inhibited the growth, migration, invasion and the epithelial–mesenchymal transition (EMT) of LGG cells. METTL7B expression potentially represents a novel prognostic biomarker due to its significant association with immune cell infiltration in LGG.

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Section: Discussionmentioning

confidence: 99%

METTL7B is a novel prognostic biomarker of lower-grade glioma based on pan-cancer analysis

Jiang

Zhu³

et al. 2021

Cancer Cell Int

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“…This recommendation is emphasized by the recent evidence of MSI as a predictive factor for response to ICI [ 18 ]. For example, the Food and Drug Administration has recently approved pembrolizumab as first-line therapy for MSI-H/dMMR metastatic colorectal cancer [ 19 ]. The prevalence of MSI-H/dMMR deficiency differs between gastrointestinal cancers.…”

Section: Discussionmentioning

confidence: 99%

“…The prevalence of MSI-H/dMMR deficiency differs between gastrointestinal cancers. It occurs most frequently in colorectal (up to 15%) and gastric cancer (about 10%) [ 19 ], and less frequently in hepatocellular-/cholangiocarcinoma and esophageal and pancreatic adenocarcinoma (< 5%) [ 19 ]. With the dramatic response of MSI-H/dMMR-deficient tumors to ICI, MSI/MMR testing has, however, increased significantly in many solid tumors.…”

Section: Discussionmentioning

confidence: 99%

Expression of Mismatch Repair Proteins in Merkel Cell Carcinoma

Gambichler

Rached

Tannapfel

et al. 2021

Cancers

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We aimed to assess for the first time the mismatch repair (MMR) protein expression in Merkel cell carcinoma (MCC). Immunohistochemistry was performed for MLH1, MSH2, MSH6, and PMS2 on patients’ tumor tissue (n = 56), including neighbored healthy control tissue. In cases with low-level MMR expression (<10th percentile), we performed multiplex PCR in combination with high-resolution capillary electrophoresis in order to confirm microsatellite instability (MSI). Microscopic evaluation revealed a high median expression for all MMR proteins studied (91.6–96.3%). However, six patients (56/10.7%) had low-level MLH1 expression, six (55/10.9%) had low-level MSH2 expression, five (56/8.9%) had low-level MSH6 expression, and six (54/11.1%) had low-level PMS2 expression. Together, we observed nine (56/16.1%) patients who had low-level MMR expression of at least one protein. Of the patients with low-level MMR expression, MSI evaluation was possible in five cases, revealing one case with high-level MSI. In all MMR proteins assessed, low-level expression was significantly (p = 0.0004 to p < 0.0001) associated with a negative Merkel cell polyomavirus (MCPyV) status. However, the expression profiles of the MMR proteins did not correlate with clinical outcome measures such as disease relapse or death (p > 0.05). MCC appears to be a malignancy characterized by low-level MMR rather than completely deficient MMR in a subset of cases, predominantly affecting MCPyV-negative tumors. Future studies will establish whether this subset of MCC patients respond better to immune checkpoint inhibitor therapy.

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“…ICIs are a type of immunotherapy with demonstrated efficacy and safety in multiple cancers ( He and Xu, 2020 ). Patients with high TMB or MSI are more likely to experience long-term survival benefits from immunotherapy ( Samstein et al, 2019 ; Zhu et al, 2021 ). To date there have been no studies on the relationship between TMB and MSI and PBK expression in cancers.…”

Section: Discussionmentioning

confidence: 99%

Omics- and Pharmacogenomic Evidence for the Prognostic, Regulatory, and Immune-Related Roles of PBK in a Pan-Cancer Cohort

Liu

Xiang

Peng

et al. 2021

Front. Mol. Biosci.

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PDZ-binding kinase (PBK) is known to regulate tumor progression in some cancer types. However, its relationship to immune cell infiltration and prognosis in different cancers is unclear. This was investigated in the present study by analyzing data from TCGA, GEO, GETx, TIMER, CPTAC, GEPIA2, cBioPortal, GSCALite, PROGNOSCAN, PharmacoDB, STRING, and ENCORI databases. PBK was overexpressed in most tumors including adenocortical carcinoma (hazard ratio [HR] = 2.178, p < 0.001), kidney renal clear cell carcinoma (KIRC; HR = 1.907, p < 0.001), kidney renal papillary cell carcinoma (HR = 3.024, p < 0.001), and lung adenocarcinoma (HR = 1.255, p < 0.001), in which it was associated with poor overall survival and advanced pathologic stage. PBK methylation level was a prognostic marker in thyroid carcinoma (THCA). PBK expression was positively correlated with the levels of BIRC5, CCNB1, CDC20, CDK1, DLGAP5, MAD2L1, MELK, PLK1, TOP2A, and TTK in 32 tumor types; and with the levels of the transcription factors E2F1 and MYC, which regulate apoptosis, the cell cycle, cell proliferation and invasion, tumorigenesis, and metastasis. It was also negatively regulated by the microRNAs hsa-miR-101-5p, hsa-miR-145-5p, and hsa-miR-5694. PBK expression in KIRC, liver hepatocellular carcinoma, THCA, and thymoma was positively correlated with the infiltration of immune cells including B cells, CD4+T cells, CD8+ T cells, macrophages, monocytes, and neutrophils. The results of the functional enrichment analysis suggested that PBK and related genes contribute to tumor development via cell cycle regulation. We also identified 20 drugs that potentially inhibit PBK expression. Thus, PBK is associated with survival outcome in a variety of cancers and may promote tumor development and progression by increasing immune cell infiltration into the tumor microenvironment. These findings indicate that PBK is a potential therapeutic target and has prognostic value in cancer treatment.

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Management of Non-Colorectal Digestive Cancers with Microsatellite Instability

Cited by 11 publications

References 172 publications

METTL7B is a novel prognostic biomarker of lower-grade glioma based on pan-cancer analysis

METTL7B is a novel prognostic biomarker of lower-grade glioma based on pan-cancer analysis

Expression of Mismatch Repair Proteins in Merkel Cell Carcinoma

Omics- and Pharmacogenomic Evidence for the Prognostic, Regulatory, and Immune-Related Roles of PBK in a Pan-Cancer Cohort

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