MYC Up-regulation Is a Useful Biomarker for Preoperative Neoadjuvant Chemotherapy Combined With Anti-EGFR in Liver Metastasis from Colorectal Cancer

Kato, Takazumi; Matsuhashi, Nobuhisa; Tomita, Hiroyuki; Takahashi, Tsuyoshi; Iwata, Yoshinori; Fukada, Masahiro; Yasufuku, Itaru; Suetsugu, Tomonari; Imai, Takeharu; Mori, Rintaro; Imai, Hisashi; Tanaka, Yoshihiro; Okumura, Naoki; Hara, Akira; Yoshida, Kazuhiro

doi:10.21873/invivo.12249

Cited by 6 publications

(4 citation statements)

References 23 publications

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“…For example, cancer cells were sensitive to oxaliplatin with the elevated expression of MYC, whereas they were insensitive with the increased expression of ACSS2. MYC upregulation is a valuable biomarker for neoadjuvant chemotherapy in primary colorectal cancer with liver metastasis (39). These findings might be excellent markers for assessing the response to targeted therapy to facilitate the development of personalized treatment for osteosarcoma.…”

Section: B Amentioning

confidence: 99%

Comprehensive analysis of fatty acid and lactate metabolism–related genes for prognosis value, immune infiltration, and therapy in osteosarcoma patients

Han²,

Su³

et al. 2022

Front. Oncol.

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Osteosarcoma is the most frequent bone tumor. Notwithstanding that significant medical progress has been achieved in recent years, the 5-year overall survival of osteosarcoma patients is inferior. Regulation of fatty acids and lactate plays an essential role in cancer metabolism. Therefore, our study aimed to comprehensively assess the fatty acid and lactate metabolism pattern and construct a fatty acid and lactate metabolism–related risk score system to predict prognosis in osteosarcoma patients. Clinical data and RNA expression data were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases. We used the least absolute shrinkage and selection operator (LASSO) and Cox regression analyses to construct a prognostic risk score model. Relationships between the risk score model and age, gender, tumor microenvironment characteristics, and drug sensitivity were also explored by correlation analysis. We determined the expression levels of prognostic genes in osteosarcoma cells via Western blotting. We developed an unknown fatty acid and lactate metabolism–related risk score system based on three fatty acid and lactate metabolism–related genes (SLC7A7, MYC, and ACSS2). Survival analysis showed that osteosarcoma patients in the low-risk group were likely to have a better survival time than those in the high-risk group. The area under the curve (AUC) value shows that our risk score model performs well in predicting prognosis. Elevated fatty acids and lactate risk scores weaken immune function and the environment of the body, which causes osteosarcoma patients’ poor survival outcomes. In general, the constructed fatty acid and lactate metabolism–related risk score model can offer essential insights into subsequent mechanisms in available research. In addition, our study may provide rational treatment strategies for clinicians based on immune correlation analysis and drug sensitivity in the future.

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Section: B Amentioning

confidence: 99%

Comprehensive analysis of fatty acid and lactate metabolism–related genes for prognosis value, immune infiltration, and therapy in osteosarcoma patients

Han²,

Su³

et al. 2022

Front. Oncol.

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“…Recent studies reported an association of circulating tumor DNA (ctDNA) with recurrence in patients with CRC, and a strategy based on ctDNA detection was recommended (40) (41). We also reported previously that MYC up-regulation is a useful biomarker for selecting anti-EGFR combination therapy in PC for CRLMs (42), and evaluation of genomic information has become essential in planning CRC treatment.…”

Section: Discussionmentioning

confidence: 86%

The Prognostic Significance of a Histological Response to Preoperative Chemotherapy in Patients With Synchronous Colorectal Liver Metastases

Tanaka

Imai

Matsuhashi

et al. 2021

International Surgery

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Objective: Preoperative chemotherapy (PC) for colorectal liver metastasis (CRLM) is widely used to improve prognosis, but its clinical benefit has not been fully established. This study aimed to assess the effectiveness of PC for synchronous CRLM and the correlation between the histological response to PC and survival. Summary of Background Data: We enrolled 69 patients who underwent initial hepatectomy for synchronous CRLM between 2004 and 2018 at Gifu University Hospital. Methods: We retrospectively analyzed the clinicopathological factors and outcomes of 69 patients who underwent hepatectomy after receiving PC (PC group: n = 43) or who underwent upfront hepatectomy (non-PC group: n = 26). In the PC group, the patients were divided into the Grade 1 (n = 27) and Grade 2/3 (n = 16) groups according to their histological responses to PC. Results: The median survival and 5-year overall survival (OS) rates were 80.9 months and 61.5%, respectively, in the PC group and 71.7 months and 61.5%, respectively, in the non-PC group ( P = 0.867). Regarding recurrence-free survival (RFS) and remnant liver-RFS, there were no significant differences between the two groups ( P = 0.087 and 0.291). However, in a subgroup analysis, the median 5-year OS, RFS, and remnant liver RFS were significantly longer in the Grade 2/3 than Grade 1 group ( P = 0.008, P = 0.002, and P < 0.001, respectively). Conclusions: Some patients benefit from PC, and the histological response to PC had prognostic significance for patients with synchronous CRLM.

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“…In this study, genomic alterations of the Myc pathway, all of which were MYC amplification, were identified in 13 of 128 Taiwanese patients with mCRC. Several investigators examined the clinical impact of Myc expression on CRC; however, this evidence remains inconclusive [ 38 , 39 , 40 , 41 , 42 ]. The prognostic impact discordance between these studies is related to distinct analytic tools in Myc expression detection (e.g., immunohistochemistry and in situ hybridization), patients with dissimilar disease stages, and limited sample size.…”

Section: Discussionmentioning

confidence: 99%

Association between Altered Oncogenic Signaling Pathways and Overall Survival of Patients with Metastatic Colorectal Cancer

Huang

Lin

et al. 2021

Diagnostics

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Systemic characterization of genomic alterations into signaling pathways helps to understand the molecular pathogenies of colorectal cancer; however, their clinical implications remain unclear. Here, 128 patients with metastatic colorectal cancer (mCRC) receiving targeted next generation sequencing were retrospectively enrolled to analyze the impact of altered oncogenic pathways on clinical outcome. The datasets from Memorial Sloan Kettering Cancer Center were used for validation. In 123 patients with non-MSI-high tumor, the most common mutated gene was TP53 (84.6%), followed by APC (78.0%), KRAS (49.6%), and SMAD4 (22.8%). When mutated genes were allocated into signaling pathways defined as The Cancer Genome Atlas Pan-Cancer Analysis Project, alterations of cell cycle, Wnt, p53, RTK-RAS, PI3K, TGF-β, Notch, and Myc pathways were identified in 88%, 87%, 85%, 75%, 28%, 26%, 17%, and 10% of mCRC tissues, respectively. The survival analyses revealed that Myc and TGF-β pathway alterations were associated with a shorter overall survival (OS) (hazard ratio [HR]: 2.412; 95% confidence interval [CI]: 1.139–5.109; p = 0.018 and HR: 2.754; 95% CI: 1.044–7.265; p = 0.033, respectively). The negative prognostic impact of altered TGF-β pathway was maintained in patients receiving an anti-EGFR antibody. The OS of patients with mCRC carrying MYC and BRAF mutation was shorter than those with either MYC or BRAF mutation (HR: 4.981, 95% CI: 0.296–83.92; p = 0.02). These findings have clinical implications, such as prognosis prediction, treatment guidance, and molecular-targeted therapy development.

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MYC Up-regulation Is a Useful Biomarker for Preoperative Neoadjuvant Chemotherapy Combined With Anti-EGFR in Liver Metastasis from Colorectal Cancer

Cited by 6 publications

References 23 publications

Comprehensive analysis of fatty acid and lactate metabolism–related genes for prognosis value, immune infiltration, and therapy in osteosarcoma patients

Comprehensive analysis of fatty acid and lactate metabolism–related genes for prognosis value, immune infiltration, and therapy in osteosarcoma patients

The Prognostic Significance of a Histological Response to Preoperative Chemotherapy in Patients With Synchronous Colorectal Liver Metastases

Association between Altered Oncogenic Signaling Pathways and Overall Survival of Patients with Metastatic Colorectal Cancer

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