Correlations between microsatellite instability and the biological behaviour of tumours

Yang, Guang; Zheng, Ru-yi; Jin, Zaishun

doi:10.1007/s00432-019-03053-4

Cited by 110 publications

(93 citation statements)

References 55 publications

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“…Other than TMB, many signatures could also be applied to predict the response to immunotherapy in patients with cancer [ 4 , 5 , 20 – 22 ]. For example, microsatellite instability (MSI), caused by a deficient DNA mismatch repair system, could identify good responders to immunotherapy in multiple cancers [ 23 ]. Alternatively, higher expression of PDL1 also predicted better efficacy of immunotherapy across many cancers [ 6 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Role of tumor mutation burden-related signatures in the prognosis and immune microenvironment of pancreatic ductal adenocarcinoma

et al. 2021

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Background High tumor mutation burden (TMB) has gradually become a sensitive biomarker for predicting the response to immunotherapy in many cancers, including lung, bladder and head and neck cancers. However, whether high TMB predicts the response to immunotherapy and prognosis in pancreatic ductal adenocarcinoma (PDAC) remained obscure. Hence, it is significant to investigate the role of genes related to TMB (TRGs) in PDAC. Methods The transcriptome and mutation data of PDAC was downloaded from The Cancer Genome Atlas-Pancreatic Adenocarcinoma (TCGA). Five independent external datasets of PDAC were chosen to validate parts of our results. qRT-PCR and immunohistochemical staining were also performed to promote the reliability of this study. Results The median overall survival (OS) was significantly increased in TMB_low group compared with the counterpart with higher TMB score after tumor purity adjusted (P = 0.03). 718 differentially expressed TRGs were identified and functionally enriched in some oncogenic pathways. 67 TRGs were associated with OS in PDAC. A prognostic model for the OS was constructed and showed a high predictive accuracy (AUC = 0.849). We also found TMB score was associated with multiple immune components and signatures in tumor microenvironment. In addition, we identified a PDAC subgroup featured with TMBlowMicrosatellite instabilityhigh (MSIhigh) was associated with prolonged OS and a key molecule, ANKRD55, potentially mediating the survival benefits. Conclusion This study analyzed the biological function, prognosis value, implications for mutation landscape and potential influence on immune microenvironment of TRGs in PDAC, which contributed to get aware of the role of TMB in PDAC. Future studies are expected to investigate how these TRGs regulate the initiation, development or repression of PDAC.

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Section: Introductionmentioning

confidence: 99%

Role of tumor mutation burden-related signatures in the prognosis and immune microenvironment of pancreatic ductal adenocarcinoma

et al. 2021

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“…Microsatellite instability detection plays an essential role in tumor research [ 32 ], as does MSI status evaluation for each tumor. However, neither MSI-H or MSI-L were observed in the tumor, regardless of GI cancer type ( Table 2 ).…”

Section: Discussionmentioning

confidence: 99%

Investigation of an Alternative Marker for Hypermutability Evaluation in Different Tumors

Chen

Zhang

Xiong

et al. 2021

Genes

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A growing number of studies have shown immunotherapy to be a promising treatment strategy for several types of cancer. Short tandem repeats (STRs) have been proven to be alternative markers for the evaluation of hypermutability in gastrointestinal (GI) cancers. However, the status of STRs and microsatellite instability (MSI) in other tumors have not yet been investigated. To further compare STR and MSI alterations in different tumors, a total of 407 paired DNAs were analyzed from the following eight tumor types: breast cancer (BC), hepatocellular cancer (HCC), pancreatic cancer (PC), colorectal cancer (CRC), gastric cancer (GC), lung cancer (LC), esophageal cancer (EC), and renal cell cancer (RCC). The STR alteration frequencies varied in different tumors as expected. Interestingly, none of the patients possessed MSI-low (MSI-L) or MSI-high (MSI-H), except for the GI patients. The highest STR alteration was detected in EC (77.78%), followed by CRC (69.77%), HCC (63.33%), GC (54.55%), LC (48.00%), RCC (40.91%), BC (36.11%), and PC (25.71%). The potential cutoff for hypermutability was predicted using the published objective response rate (ORR), and the cutoff of LC and HCC was the same as that of GI cancers (26.32%). The cutoffs of 31.58% and 10.53% should be selected for BC and RCC, respectively. In summary, we compared MSI and STR status in eight tumor types, and predicted the potential threshold for hypermutability of BC, HCC, CRC, GC, LC, EC, and RCC.

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“…Fourthly, selection bias might exist after the case screening. Besides, there were no information of their genotypes, genetic data among these histologic subtypes that may be the prognosis factors, such as human epidermalgrowth-factor receptor 2 (HER-2), Microsatellite instable (MSI) and Epstein Barr Virus (EBV) [21][22][23].…”

Section: Discussionmentioning

confidence: 99%

Adenocarcinoma with mixed subtypes in the early and advanced gastric cancer.

Zhao

Yang

et al. 2021

Preprint

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Background Based on the WHO classification, adenocarcinoma with mixed subtypes (AM) is a histological classification. We aimed to compare the prognosis among AM, classic adenocarcinoma (CA), mucinous adenocarcinoma (MAC), and signet-ring cell carcinoma (SRCC) in early and advanced gastric cancer (EGC, AGC), respectively. Methods We compared the clinicopathologic features and prognosis between AM and other histologic subtypes of CA, SRCC and MAC in ECG and ACG, respectively. A nomogram was established to predict the cancer-specific survival (CSS) of gastric cancer (GC) patients with AM. C-index, calibration curves, Receiver Operating Characteristic (ROC) and Decision Curve Analysis (DCA) curves were applied to examine the accuracy and clinical benefits. Results In the prognosis among these four histological subtypes in EGC patients, there are no differences. For AGC patients, AM had a significantly poorer prognosis compared with CA and MAC (P = 0.003, 0.029), but similar prognosis to SRCC. A nomogram based on race, T stage, N stage, M stage and surgical modalities were proposed to predict 1- and 3- year CSS for GC patients with AM (C-index: training cohort: 0.804, validation cohort: 0.748. 1-, 3-year CSS AUC: training cohort: 0.871, 0.914, validation cohort: 0.810, 0.798). 1- and 3-year CSS DCA curves showed good net benefits. Conclusions EGC patients with AM had similar survival to those with CA, MAC and SRCC. AM was an independent predictor of poor prognosis in AGC. A nomogram for predicting the prognosis of GC patients with AM was proposed to quantitatively assess the long-term survival.

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Correlations between microsatellite instability and the biological behaviour of tumours

Cited by 110 publications

References 55 publications

Role of tumor mutation burden-related signatures in the prognosis and immune microenvironment of pancreatic ductal adenocarcinoma

Role of tumor mutation burden-related signatures in the prognosis and immune microenvironment of pancreatic ductal adenocarcinoma

Investigation of an Alternative Marker for Hypermutability Evaluation in Different Tumors

Adenocarcinoma with mixed subtypes in the early and advanced gastric cancer.

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