Clinicopathologic and Prognostic Association of GRP94 Expression in Colorectal Cancer with Synchronous and Metachronous Metastases

Patients with advanced colorectal cancer (CRC) with distant metastases have a poor prognosis. We evaluated the clinicopathological relevance of GRP94 expression in these cases. The immunohistochemical expression of GRP94 was studied in 189 CRC patients with synchronous (SM; n = 123) and metachronous metastases (MM; n = 66), using tissue microarray; the association between GRP94 expression, outcome, and tumor-infiltrating lymphocytes (TILs) was also evaluated. GRP94 was expressed in 64.6% (122/189) patients with CRC; GRP94 positivity was found in 67.5% and 59.1% patients with SM and MM, respectively. In the SM group, high GRP94 expression was more common in patients with a higher density of CD4+ TILs (p = 0.002), unlike in the MM group. Survival analysis showed that patients with GRP94 positivity had significantly favorable survival (p = 0.030); after multivariate analysis, GRP94 only served as an independent prognostic factor (p = 0.034; hazard ratio, 0.581; 95% confidence interval, 0.351–0.961) in the SM group. GRP94 expression was detected in 49.4% of metastatic sites and showed significant heterogeneity between primary and metastatic lesions (p = 0.012). GRP94 is widely expressed in CRC with distant metastases; its expression was associated with favorable prognosis in the SM group, unlike in the MM group.

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Review for "Relationship between T cell receptor clonotype and PD‐1 expression of tumor‐infiltrating lymphocytes in colorectal cancer"

10.1002/eji.201948399/v2/review1 ◽

2020 ◽

Author(s):

Lei Zhang

Keyword(s):

Colorectal Cancer ◽

T Cell ◽

T Cell Receptor ◽

Tumor Infiltrating Lymphocytes ◽

Cell Receptor ◽

Infiltrating Lymphocytes

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Identification of biomarkers related to Tumor-Infiltrating Lymphocytes (TILs) infiltration with gene co-expression network in colorectal cancer

Bioengineered ◽

10.1080/21655979.2021.1921551 ◽

2021 ◽

Vol 12 (1) ◽

pp. 1676-1688

Author(s):

Rong Liao ◽

Qi-Zhi Ma ◽

Cong-Ya Zhou ◽

Jun-Jun Li ◽

Ning-Na Weng ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Infiltrating Lymphocytes ◽

Infiltrating Lymphocytes

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Perioperative beta-adrenergic blockade and COX2 inhibition in colorectal cancer patients improves pro-metastatic indices in the excised tumor: EMT, tumor infiltrating lymphocytes (TILs), and gene regulatory pathways

Brain Behavior and Immunity ◽

10.1016/j.bbi.2017.07.046 ◽

2017 ◽

Vol 66 ◽

pp. e9 ◽

Cited By ~ 6

Author(s):

R. Haldar ◽

I. Ricon ◽

S. Cole ◽

O. Zmora ◽

S. Ben-Eliyahu

Keyword(s):

Colorectal Cancer ◽

Cancer Patients ◽

Tumor Infiltrating Lymphocytes ◽

Adrenergic Blockade ◽

Beta Adrenergic ◽

Regulatory Pathways ◽

Gene Regulatory ◽

Colorectal Cancer Patients ◽

Infiltrating Lymphocytes

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Association of KMT2C/D loss-of-function mutations with tumor infiltrating lymphocytes and response to immune checkpoint inhibitors in solid tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.2587 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 2587-2587

Author(s):

Ruiqi Liu ◽

Yanling Niu ◽

Xin Zhang ◽

Tonghui Ma

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

T Cells ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Tumor Infiltrating Lymphocytes ◽

Loss Of Function ◽

Cancer Types ◽

Immune Related Genes ◽

Infiltrating Lymphocytes

2587 Background: Dysregulation of HMTs plays an important role in tumorigenesis. KMT2C and KMT2D are enzymatically active scaffold proteins that form the core of mammalian COMPASS complexes, which methylate the histone 3 lysine 4. Both KMT2C and KMT2D are involved in the regulation of gene expression. Therefore, we explored the associations of KMT2C/D loss-of-function (LOF) mutations with the expression of immune-related genes, the levels of tumor infiltrating lymphocytes (TILs), and response to immune checkpoint inhibitors (ICIs). Methods: KMT2C/D LOF mutations were defined as nonsense, frameshift, splice site variants within consensus regions, start lost, and stop lost/gained variants. An ICIs treatment cohort from the MSKCC was used for exploring the associations between KMT2C/D LOF mutations and ICIs efficacy. The RNA-Seq data obtained from the TCGA cohort was used for analysis of gene expression and the levels of TILs using CIBERSORT. Results: In MSKCC pan-cancer dataset, patients with KMT2C/D LOF mutations had a relatively longer median overall survival (OS) compared to those with non-LOF mutations, although the result did not reach statistical significance (P = 0.0832). Then we analyzed the predictive roles of KMT2C/D LOF mutations for each cancer type. The results showed that the predictive role of KMT2C/D LOF mutations for the clinical efficacy of ICIs therapy was only observed in colorectal cancer (P = 0.045). However, we did not find the associations of KMT2C/D LOF mutations with ICIs efficacy in bladder cancer, breast cancer, melanoma, glioma, head and neck cancer, renal cell carcinoma, NSCLC, and esophagogastric cancer. Consistently, analysis of TILs in colorectal cancer revealed that KMT2C/D LOF was associated with increased infiltration of several types of immune cells, such as CD8+ T cells (P = 0.0001), activated NK cells (P = 0.0001), M1 macrophage (P = 0.0005), M2 macrophage (P = 0.0115), and neutrophils (P = 0.0209). Meanwhile, regulatory T cells (Tregs) (P = 0.0048) and M0 macrophage (P = 0.0043) were dramatically decreased in KMT2C/D LOF group for colorectal cancer. Moreover, there were no significant relationships between KMT2C/D LOF and the levels of TILs in other cancer types. Our data also demonstrated that KMT2C and KMT2D could regulate the expression of more than 30 immune-related genes in colorectal cancer. Conclusions: Our data indicated that KMT2C/D LOF mutations were significantly correlated with better outcomes of ICIs therapy in colorectal cancer, suggesting it can be as a useful predictor for response to ICIs in colorectal cancer. Meanwhile, we found the associations of KMT2C/D LOF with the levels of TILs in colorectal cancer, but not in other cancer types, indicating that the efficacy of ICIs was consistent with the levels of TILs.

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