The Clinical and Theranostic Values of Activated Leukocyte Cell Adhesion Molecule (ALCAM)/CD166 in Human Solid Cancers
Abstract
:Simple Summary
Abstract
1. Introduction
2. ALCAM, Its Discovery and Cellular Connections
3. ALCAM Expression Pattern in Cells and Tissues and Influence on Other Genetic and Biochemical Events
4. ALCAM Protein as a Receptor for Tumour Cell Homing
5. ALCAM Expression and Its Functional Influence in Cancer Cells
6. ALCAM Expression in Human Solid Malignant Tumours and the Clinical/Prognostic Significance
6.1. Pancreatic Cancer
6.2. Colorectal Cancer
6.3. Gastric Cancer
6.4. Breast Cancer
6.5. Sarcomas
6.6. Myeloma
6.7. Prostate Cancer
6.8. Thyroid Cancers
6.9. Ovarian Cancer
6.10. Endometrial Cancers
6.11. Hepatocellular Carcinoma
6.12. Neurological Cancers
6.13. Lung Cancer
6.14. Mesothelioma
6.15. Oesophageal Cancer
6.16. Head and Neck SCC (HNSCC) and Laryngeal Squamous Cell Carcinoma (SCC)
6.17. Cutaneous Melanoma
6.18. Oral Squamous Cell Carcinoma
6.19. Bladder Cancer
7. ALCAM and Cancer Metastasis
7.1. Liver Metastases
7.2. Brain Metastasis
7.3. Lung Metastases
7.4. Skin Metastasis
8. Circulating and Soluble ALCAM
9. ALCAM and Diagnostic and Therapeutic Considerations
9.1. ALCAM as a Therapeutic Target
9.2. Truncated ALCAM
9.3. Targeting ALCAM Partner Proteins
9.4. ALCAM as Therapeutic Response Indicator
9.5. ALCAM and Chemoresistance
10. Conclusions and Perspectives
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Tumour Type | Study Methods | Findings | References |
---|---|---|---|
Colorectal cancer | IHC (n = 111) | Both membranous and cytoplasmic staining of ALCAM are seen in colon cancer tissues. However, membranous ALCAM is linked with shortened survival of the patients. | [36] |
IHC (n = 9 pairs) | Tumour tissues showed highly stained ALCAM compared with normal tissues. | [37] | |
IHC and PCR (n = 58) | ALCAM-positive staining is seen in 43%. ALCAM-negative tumours had greater incidence of lymph node metastasis, a link greatly increased when there is concurrent KRAS mutation. | [38] | |
IHC (n = 112) | High levels of ALCAM were associated with longer recurrence-free survival. | [39] | |
Gene expression (n = 250), IHC (n = 105) and ELISA (n = 91) | ALCAM is highly expression in tumour tissues and is linked to shorter survival of the patients. | [40] | |
IHC (n = 299) | More than 70% and 60% of primary and secondary tumours stained positive for ALCAM, respectively. Positive ALCAM staining is a positive prognostic factor for the patients. | [41] | |
Gene array (n = 64) | ALCAM transcripts were significantly raised in colorectal tissues compared with normal tissues. | [42] | |
Germline polymorphism of peripheral blood of patients who resisted 5-FU therapies (n = 234) | Polymorphisms of ALCAM, along with LGR5, CD44, and ALDH1, form an independent signature in predicting the time to recurrence of patients with colon cancer who received 5-FU-based chemotherapies. | [43] | |
Metastatic liver tumours from colorectal cancer | Paired primary and secondary (n = 9 pairs), IHC | Stepwise increase in ALCAM protein from normal colorectal tissues, primary colorectal cancer tissues to metastatic liver tumours. | [37] |
Oesophageal SCC | IHC (n = 299) | High levels of ALCAM in primary tumours associated with recurrence-free and overall survival of the patients. | [44] |
IHC (n = 65) | ALCAM staining was seen in 87.69% of tumours, compared with negative staining in control normal tissues. ALCAM linked to tumour grade, TNM staining, and survival. | [45] | |
IHC and PCR (n = 65) | ALCAM expression is increased in SCC compared with control tissues, and the increase is seen with nodal metastasis and late clinical stages. | [46] | |
Laryngeal, head, and neck SCC | IHC and RNAseq (n = 44) and gene array | Membranous staining of ALCAM. High levels of staining associated with shorter survival of the patients. | [47] |
IHC (n = 400) | A total of 70% of HNSCC tumours stained positive for ALCAM, including 12.4% membranous, 40.1% cytoplasmic, and mixed membranous/cytoplasmic in 17.9%. | [48] | |
IHC (n = 96) | Patients with high levels of ALCAM staining in HNSCC (n = 96) had shorter survival. Primary HNSCC (n = 68) had significantly lower ALCAM staining than the recurrent HNSCC (n = 36) tumours. | [49] | |
Oral dysplasia and cancer | IHC (n = 105) | ALCAM total and cytoplasmic staining were correlated with loss of membranous E-cadherin and beta-catenin in oral squamous cell carcinoma. ALCAM expression together with cytoplasmic/nucleus beta-catenin is an indicator of nodal metastasis and late-stage tumours. | [50] |
Oral melanoma | IHC (n = 35) | ALCAM-positive staining in oral melanoma is associated with vascular invasion. | [51] |
Non-small cell lung cancer and brain metastasis | IHC (n = 143 comprised of 51 primary NSCLC, 15 metastatic nodes and 76 metastatic brain tumours) | Metastatic brain tumours and metastatic lymph nodes stained higher for ALCAM compared with primary NSCLC. High staining in NSCLC and in metastatic brain lesions associated with poor survival. | [11] |
Breast cancer | IHC and QPCR (n = 120 tumour and 32 normal) | ALCAM transcript expression was lower in tumours with lymph node metastasis compared to those without. ALCAM levels were also lower in high-grade/TNM stage compared to lower stage/grade samples. ALCAM levels were lower in those with poorer outcomes. | [52] |
IHC (n = 162) | Cytoplasmic staining of ALCAM is associated with shorten survival, nodal status, and early recurrence. | [53] | |
Protein blotting (n = 160) and gene microarray | Neither protein nor mRNA expressions are linked to pathological factors. Protein ALCAM is seen more in ER-positive tumours. High levels of ALCAM mRNA, when receiving chemotherapy, have better clinical survival, but those who did not receive chemotherapy had worse survival. | [54] | |
Gene microarray(n = 481) | Low ALCAM expression, together with the status of ER, Her2, and osteopontin, identified a set of patients with markedly shorter survival from three separate cohorts with combined number of 481 patients. | [55] | |
GWS (6,669) | ALCAM is a new foci associated with breast cancer (Japan), and together with CLIC6-RUNX1, it makes susceptibility SNPs of breast cancer. | [56] | |
IHC (n = 153) | ALCAM is largely membranous when present. Seventy out of 153 stained positive for ALCAM and the remaining 83 negatives, and the staining has an intimate relationship with the levels of Wnt5a. | [15] | |
IHC and microarray (n = 110) | Patients with high levels of ALCAM transcript had longer disease-free survival. The correlation is more significant in patients with high levels of membranous ALCAM and high levels of mannonidase (MAN1A). | [57] | |
Transcript analysis and IHC (n = 47) | Breast tumour tissues had higher levels of ALCAM gene methylation than normal tissues, and the raised ALCAM gene methylation was seen with lower levels of ALCAM transcript. | [58] | |
IHC (n = 161) | Patients had highly raised circulating levels of soluble ALCAM and had a potential diagnostic value of breast cancer amongst the particular ethnic population (Saudi patients). | [59] | |
IHC (n = 2,197) | Reduced/loss of ALCAM staining was seen in most tumour types and was linked to high tumour grade and poor OS and RFS. | [60] | |
Pancreatic cancer | Circulating cancer cells (CTC) (n = 20) | Patients with circulating cancer cells showing high levels of ALCAM had shorter survival. | [61] |
IHC (n = 264) and ELISA (n = 116) | At the tissue level, there was no significant correlation between tumour grade and staging. However, the circulating levels of ALCAM were significantly higher than the control and those with pancreatitis. | [62] | |
IHC (n = 97) | Patients who died of pancreatic cancer had high levels of ALCAM staining in pancreatic cancer cells. | [14] | |
IHC (n = 98) | A total of 12% of pancreatic cancers were positive for ALCAM staining, compared with none in normal pancreatic tissues. | [63] | |
Ampulla of Vater | IHC | In a rather large series of this uncommon cancer, there was a progressive increase in ALCAM staining from normal mucosa (n = 152) to adenoma (n = 111) to carcinoma of ampulla of Vater (n = 175). | [64] |
Lung cancer | IHC (n = 147 NSCLC) | Membrane ALCAM staining is seen in 44.9% of NSCLC tumours and is an independent prognostic factor for shorter overall survival of the patients. | [65] |
Small intestinal adenocarcinoma | IHC (n = 191) | A total of 42% of the tumours stained positive. | [66] |
Ovarian cancer | IHC (n = 204) | Concurrent high levels of ALCAM and mannosidase MAN1A1 linked to shorter relapse-free survival of the patients, yet low levels of MAN1A1 and high levels of ALCAM linked to better survival of the patients. | [13] |
IHC (n = 109) | Cytoplasmic staining or loss of membrane staining of ALCAM is a prognostic factor for patients with ovarian cancer. | [67] | |
Endometrial cancer | IHC | For early endometrioid endometrial cancer (n = 174), positive ALCAM (76.2%) is seen in patients with short recurrence-free survival. Of all the tumours (n = 116), 67.4% stained positive for ALCAM with remaining negative. Weak or negative staining was seen at the invading front of cancer tissues. | [68,69] |
Oral squamous cell carcinoma (OSCC) | IHC (n = 41) | Staining of ALCAM on the membrane of the leading front of the SCC cells was seen in tumours with node involvement and high tumour grade. | [70] |
IHC (n = 101) | Less than half (47.5%) of the oral SCC tumours stained positive for ALCAM. | [16] | |
IHC (n = 107) | Membranous and cytoplasmic staining was seen in OSCC. Cytoplasmic staining was associated with clinical outcomes and survival of the patients. | [32] | |
Giant cell bone tumours | IHC (n = 64) | Patients with high levels of ALCAM staining in the giant cell tumour had shorter disease-free survival. | [71] |
Bladder cancer | TCGA analysis and cell work | Bladder cancer cells and bladder tumour tissues expressed high levels of an ALCAM variant (ALCAM-iso2), which is subject to easy shedding in response to MMP14. | [72] |
IHC (n = 198) and ELISA (n = 120) | Bladder tumours had reduced ALCAM staining with increased staging. Both circulating and urinary soluble ALCAM seen to markedly increase in patients with bladder cancer. | [73] | |
Thyroid cancer | IHC (n = 158) | Total ALCAM in poorly differential thyroid tumours was markedly lower than those with well/moderately differentiated tumours, and the reduction was associated with distant metastasis and shortened survival. | [74] |
Prostate cancer | IHC (n = 54 pairs) | Over 80% of tumours have raised ALCAM staining, which is largely seen in low grade and low Gleason scores. | [75] |
IHC (n = 2,390) | Approximate 70% had membrane ALCAM staining. High ALCAM expression was associated with less aggressive tumour phenotypes, pre-operative PSA (prostate-specific antigen) levels, and a reduced risk of biochemical recurrence. | [76] | |
Gene microarray and IHC (n = 42 pairs) | A total of 86% of prostate tumours are positive for ALCAM and are a prognostic marker for prostate cancer. | [77] | |
Public microarray analysis | ALCAM mRNA enhanced in metastatic disease. High mRNA expression of ALCAM corresponded with poor outcomes. | [78] | |
IHC (n = 48) and ELISA (n = 229) | Patients with metastatic disease, nodal-positive tumours, and who died from prostate cancer had high ALCAM staining. Circulating ALCAM has a prognostic value on the survival of the patients. | [79] | |
Nasopharyngeal carcinoma | ELISA (n = 60) | Patients with radioresistant response had high levels of circulating ALCAM. High staining of ALCAM is linked to favourable clinical and pathological features and with low risk of biochemical recurrence of the patients. | [80] |
Mesothelioma of the pleural cavity | IHC (n = 175) | ALCAM-positive mesotheliomas had a significantly shorter survival of the patients. | [81] |
Intracranial meningioma | IHC (n = 20) | Meningioma tissues had significantly higher levels of ALCAM compared with normal tissues. | [82] |
Neuroblastoma | IHC (n = 66) | Weak ALCAM staining is linked to a short RFS and OS. | [83] |
Glioblastoma | IHC (n = 39) | Tumours rich in ALCAM had shorter overall and disease-free survival. | [84] |
Medulloblastoma | IHC (n = 45) | Majority of the tumours (67%) were negative for ALCAM staining. The positive stained tumours (18) were seen in the WNT group and SHH group. The presence of ALCAM is associated with CTNNB1 and nuclear β-catenin expression. | [85] |
Melanoma | IHC | There is a progressively increased staining of ALCAM from nevi (15%, n = 71), primary melanoma (53%, n = 71) to metastatic melanoma (69%, n = 84). | [86] |
IHC (n = 104) | High levels of ALCAM staining seen in patients with shorter overall and disease-free survivals. In addition, low ALCAM staining in metastatic lymph nodes is also seen with shorter overall survival of the patients. | [87] | |
IHC (n = 110) | A total of 65% melanoma were positive for ALCAM compared with 74% nevi. | [88] | |
Hepatocellular carcinoma (HCC) | IHC and ELISA | HCC tumours stained more strongly for ALCAM than normal liver tissues, and HCC patients had markedly high levels of circulating HCC. | [89] |
IHC (n = 129) | In recurrent hepatocellular carcinoma (RHCC), positive ALCAM was associated with time to recurrence and microvascular invasion. | [22] | |
Salivary gland tumours | IHC (n = 45) | Adenoid cystic carcinoma and mucoepidermoid carcinoma ALCAM staining were markedly higher than benign pleomorphic adenomas and normal tissues. High-grade and late-stage malignant tumours had higher staining than early stages. | [90] |
Gastric cancer | IHC (n = 142) | Both membrane and cytoplasmic staining are present and linked to nodal metastasis and vascular invasion. | [91] |
IHC and PCR (n = 66), ELISA (n = 72) | Both protein (IHC staining) and transcript expression of ALCAM were highly raised in gastric cancer compared with control tissues. The patients also had significantly higher levels of circulating ALCAM than controls and those with non-cancerous conditions. | [92] | |
Ewing’s sarcoma | ChIP-seq and gene profiling (n = 98) | Most sarcomas stained positively for membranous ALCAM, and high levels of staining seen in patients with suitable MFS survival. Furthermore, high levels of HDGF (an ALCAM transcription suppressor) and low levels of ALCAM collectively present in patients with the worse prognosis. | [93] |
Osteosarcoma | IHC (n = 10) | Membrane and cytoplasmic staining are seen in both primary and metastatic tumours. | [94] |
Malignant mesothelioma | IHC (n = 55) | A total of 55% of the 47 malignant mesotheliomas stained positive for ALCAM. Overexpression is linked to shorter survival. | [95] |
Cervical cancer | IHC (n = 233) | Over half (58.4%) of tumours were strongly positive for ALCAM. | [96] |
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Yang, Y.; Sanders, A.J.; Dou, Q.P.; Jiang, D.G.; Li, A.X.; Jiang, W.G. The Clinical and Theranostic Values of Activated Leukocyte Cell Adhesion Molecule (ALCAM)/CD166 in Human Solid Cancers. Cancers 2021, 13, 5187. https://doi.org/10.3390/cancers13205187
Yang Y, Sanders AJ, Dou QP, Jiang DG, Li AX, Jiang WG. The Clinical and Theranostic Values of Activated Leukocyte Cell Adhesion Molecule (ALCAM)/CD166 in Human Solid Cancers. Cancers. 2021; 13(20):5187. https://doi.org/10.3390/cancers13205187
Chicago/Turabian StyleYang, Yiming, Andrew J. Sanders, Q. Ping Dou, David G. Jiang, Amber Xinyu Li, and Wen G. Jiang. 2021. "The Clinical and Theranostic Values of Activated Leukocyte Cell Adhesion Molecule (ALCAM)/CD166 in Human Solid Cancers" Cancers 13, no. 20: 5187. https://doi.org/10.3390/cancers13205187