TABLE 1.
ASC/TSM1 up- and down-regulation (methylation status) and clinical correlates in human cancers.
| Tumor type | Expression/methylation status in normal tissue | Expression/methylation status in cancer tissue | Clinical correlates | Clinical outcome | References |
| Breast cancer | Unmethylated in normal breast tissue (n = 3) | Methylation in 40% (11 of 27) of tumors and 44.4% (8 of 18) of paired adjacent tissues | NE | NE | Conway et al., 2000 |
| SCLC, NSCL, breast cancer | Unmethylated in normal lung tissue (n = 18) and 7% (2 of 30) of normal breast tissues | Methylation in 41% (13 of 32) of SCLC, 40% (28 of 70) of NCSLC and 32% (20 of 63) of breast cancer | None | NE | Virmani et al., 2003 |
| NSCLC | Methylation in 12.9% (9 of 70) of normal lung tissues | Methylation in 47.1% (33 of 70) of lung tumors | Methylation as an independent unfavorable prognostic factor | Patients with unmethylated tumors had better survival | Zhang et al., 2006 |
| Lung cancer | Expressed in normal tissue (n = 6) and pre-cancerous lesions (n = 10) Methylation in 1 of 23 pre-cancerous lesions | Reduced expression in 75% (30 of 40) of tumors Methylation in 27% (41 of 152) of tumors | Methylation correlates with lymphatic invasion, lymph node metastases and advanced stage | Methylation in sputum DNA predicts prognosis in patients resected for early stage disease | Machida et al., 2006 |
| Colorectal cancer | Methylation in 12.5% (2 of 16) normal tissue | Methylation in 25% (4 of 16) of tumors | Methylation associates with lack of nodal metastases | NE | Ohtsuka et al., 2006 |
| Colorectal cancer | Methylation in 20% (2 of 10) of adjacent normal tissues | Partial methylation in 60% (6 of 10) of tumors | NE | NE | Yokoyama et al., 2003 |
| Colorectal cancer | Unmethylated in normal tissue (n = 11) and adenomas (n = 30) | Methylation in 17% (20 of 115) of tumors | Methylation more common in right-sided tumors and in late stages | NE | Riojas et al., 2007 |
| Melanoma | Highly expressed in melanocytic nevi (n = 18) | Absent or reduced in 62.5% (20 of 32) of melanomas | NE | NE | Guan et al., 2003 |
| Melanoma | Highly expressed in normal melanocytes | Downregulated in primary (n = 6) and in metastatic lesions (n = 6) | NE | NE | Liu et al., 2013 |
| Ovarian cancer | Unmethylated in normal ovary tissue (n = 4) | Methylation in 19% (15 of 80) of tumors | Methylation correlates with clear cell-type tumors | No correlation with prognosis | Terasawa et al., 2004 |
| Ovarian cancer | NE | Methylation in 40% (8 of 20) of tumors | NE | NE | Akahira et al., 2004 |
| Glioblastoma | Expressed and unmethylated in normal brain (astrocytes) | Methylation in 43% (10 of 23) of tumors | None | Increased survival in patients with unmethylated tumors | Stone et al., 2004 |
| Glioblastoma | NE | Methylation in 21.05% (12 of 57) of tumors | Methylation increased (4 of 7) in long-term survivors | Increased survival in patients with methylated tumors | Martinez et al., 2007 |
| Neuroblastoma | NE | Methylation in 31% (45 of 145) of tumors | Methylation correlates with advanced disease | Methylation associates with reduced survival | Alaminos et al., 2004 |
| Medulloblastoma | NE | Expression in 60% (9 of 11) of tumor samples | NE | NE | Knight et al., 2015 |
| Prostate cancer | Unmethylated in normal tissues (n = 14) Methylation in 28% (11 of 40) of adjacent tissue | Methylation in 65% (38 of 58) of tumors and 64% (7 of 11) of high-grade intraepithelial neoplasia | Methylation in adjacent tissue correlates with biochemical recurrence | None | Collard et al., 2006 |
| Prostate cancer | NE | Methylation in 63.6% (42 of 66) of tumors and 35% (12 of 34) of prostate hyperplasia | Methylation more prevalent in the white race | NE | Das et al., 2006 |
| Gastric cancer | NE | Methylation in 32.1% (20 of 80) of tumors | None | Reduced survival for patients with methylation | Kato et al., 2008 |
| Gastric cancer | Expression higher than in tumor tissue and unmethylated (n = 40) | Methylation in 34% (68 of 200) of tumors | Methylation correlates with tumor size and lymph node metastases | Reduced survival for patients with methylation | Wu L. et al., 2016 |
| Gastric cancer | Expression lower than in tumors in two patient cohorts (n = 10 and n = 18) | Expression higher than in non-tumor adjacent tissues in the same patient cohorts | Correlation between ASC and IL18 mRNA levels | NE | Deswaerte et al., 2018 |
| Cervical cancer | Methylation in 2.5% (2 of 80) of non-tumor adjacent tissue | Methylation in 6.2% (5 of 80) of tumors | None | NE | Kordi Tamandani et al., 2009 |
| Renal cell carcinoma | Highly expressed in adjacent non-cancerous tissues (n = 67) Methylation in 12% of normal tissue | Downregulation in tumor compared to normal tissues (n = 67) Methylation in 41.1% (83 of 202) of tumors | Methylation correlates with higher nuclear grade | NE | Liu et al., 2015 |
| Oral squamous cell carcinoma | Highly expressed in normal oral mucosa (n = 6) | Downregulation in tumors as a function of differentiation grade | Correlation with clinical features | Better survival in patients with higher ASC score (% of positive cells) | Shimane et al., 2013 |
| Oral squamous cell carcinoma | Downregulated in normal tissue compared to tumors (n = 20) | Upregulated in tumors compared to normal mucosa (n = 111) | ASC increased expression as an independent predictor of survival | ASC expression correlated with reduced survival | Wu C.S. et al., 2016 |
| Cutaneous squamous cell carcinoma | Expressed in normal tissue | Loss of expression in de-differentiated G3 tumors | None | NE | Meier et al., 2016 |
| Pancreatic ductal adeno-carcinoma | Weak staining in adjacent non-tumor tissue (n = 41) | ASC expression in all tumor samples; i.e., 90% (37 of 41) of tumor cells and 100% of TAMs (n = 41) | NE | Increased survival in patients with ASC mRNA expression inferior to the median values | Brunetto et al., 2019 |
NE, not evaluated.