Overview of TEP mRNA cancer biomarker studies
| mRNA TEP biomarkers . | Cancer type . | Findings . | Putative predominant biomarker origin . | Detection method . | References . | Predictive value . |
|---|---|---|---|---|---|---|
| Panel of mRNAs | NSCLC | Detection of metastatic lung cancer | Endogenous | Microarray | 108 | 200 transcripts DE between NSCLC and controls with P < 1 × 10−4 |
| EGFRvIII and PCA3 | Glioma and PCa | Tumor-derived (mutant) RNAs are transferred into platelets | Transferred | RT-PCR | 95 | EGFRvIII present in 80% of the platelets derived from patients who are EGFRvIII positive |
| EML4-ALK | NSCLC | Biomarker for monitoring of chemotherapy response (crizotinib) | Transferred | qRT-PCR | 110 | RT-PCR demonstrated 65% sensitivity and 100% specificity for the detection of EML4-ALK rearrangements in platelets |
| Panel of mRNAs | NSCLC, CRC, GBM, BrCa, PAAD, HBC | Cancer detection and identification location primary tumor. Identification of MET or HER2-positive, and mutant KRAS, EGFR, or PIK3CA tumors | Endogenous | RNA-seq | 65 | 96% accuracy to distinguish patients with localized and metastasized tumors from healthy individuals; 71% accuracy to identify primary tumor location across 6 different tumor types |
| KLK2, KLK3, FOLH1, and NPY | PCa | Biomarkers for treatment response (abiraterone) | Transferred | ddPCR | 112 | Combining KLK3, FOLH1, and NPY separates long-term responders from short-term responders with 87% sensitivity and 82% specificity |
| Panel of mRNAs | NSCLC | Detection of early- and late-stage NSCLC | Endogenous | RNA-seq | 64 | Accuracy 88%, AUC 0.94, 95% CI 0.92-0.96, P < .001 for detection of late-stage NSCLC; accuracy 81%, AUC 0.89, 95% CI 0.83-0.95, P < .001 for detection of early-stage NSCLC |
| Panel of mRNAs | NSCLC | Early detection of NSCLC | Endogenous | RNA-seq | 125 | Sensitivity 0.925, specificity 0.827, accuracy 0.889, and Matthews correlation coefficients 0.760 for detection of NSCLC |
| EGFRvIII | NSCLC | Biomarker for identification of appropriate treatment selection | Transferred | RT-PCR | 109 | EGFRvIII was detected in 1.5% of all patients analyzed |
| Panel of mRNAs | MM | Transcripts involved in platelet activation, signaling, and aggregation were upregulated in SMM/MM patient platelets compared with HD platelets | Endogenous | RNA-seq | 23 | Panel of 336 transcripts increased and 441 transcripts decreased |
| ALK rearrangement | NSCLC | Diagnosis of ALK-positive NSCLC and predictive value for ALK inhibitors treatment | Transferred | RT-PCR | 111 | Accuracy 80.3% for detection of ALK rearrangements using platelets |
| ITGA2B | NSCLC | Identification of stage I NSCLC and differentiate malignant from benign lung nodules | Endogenous | RNA-seq, qRT-PCR, and ddPCR | 91 | AUC 0.888, sensitivity 91.2%, and specificity 56.5% for detection of NSCLC by qRT-PCR |
| MAX, MTURN, HLA-B | Lung cancer | Detection of early-stage lung cancer patients and predictive response of chemotherapy treatment | Endogenous | Microarray, qRT-PCR | 117 | AUC 0.734, sensitivity of 60.6%, specificity of 81.7% for detection of lung cancer patients compared with healthy controls |
| AUC 0.787, sensitivity of 72.7%, specificity of 85.4%, for detection in early-stage lung cancer compared healthy donors | ||||||
| TIMP1 | CRC | TIMP1 is expressed at high levels in CRC patients; TIMP1 mRNA can be transferred to CRC cells and promote tumor growth in vivo and in vitro | Transferred | RNA-seq and qRT-PCR | 86 | AUC 0.9583 (95%CI, 0.9363–0.9803) |
| TPM3 | BrCa | TPM3 is present at high level in patients with BrCa; TPM3 mRNA is transferred through microvescicles and enhances cancer cell migration | Transferred | RNA-seq and qRT-PCR | 85 | AUC 0.9705 (95% CI, 0.9494-0.9823) for detection of BrCa |
| AUC 0.8404 (95% CI, 0.7566-0.9242) for detection of metastatic BrCa | ||||||
| Panel of mRNAs | Sarcoma | Diagnosis of sarcoma patients | Endogenous | RNA-seq | 126 | Accuracy of 87%, AUC 0.93 (95% CI, 0.86-1) |
| mRNA TEP biomarkers . | Cancer type . | Findings . | Putative predominant biomarker origin . | Detection method . | References . | Predictive value . |
|---|---|---|---|---|---|---|
| Panel of mRNAs | NSCLC | Detection of metastatic lung cancer | Endogenous | Microarray | 108 | 200 transcripts DE between NSCLC and controls with P < 1 × 10−4 |
| EGFRvIII and PCA3 | Glioma and PCa | Tumor-derived (mutant) RNAs are transferred into platelets | Transferred | RT-PCR | 95 | EGFRvIII present in 80% of the platelets derived from patients who are EGFRvIII positive |
| EML4-ALK | NSCLC | Biomarker for monitoring of chemotherapy response (crizotinib) | Transferred | qRT-PCR | 110 | RT-PCR demonstrated 65% sensitivity and 100% specificity for the detection of EML4-ALK rearrangements in platelets |
| Panel of mRNAs | NSCLC, CRC, GBM, BrCa, PAAD, HBC | Cancer detection and identification location primary tumor. Identification of MET or HER2-positive, and mutant KRAS, EGFR, or PIK3CA tumors | Endogenous | RNA-seq | 65 | 96% accuracy to distinguish patients with localized and metastasized tumors from healthy individuals; 71% accuracy to identify primary tumor location across 6 different tumor types |
| KLK2, KLK3, FOLH1, and NPY | PCa | Biomarkers for treatment response (abiraterone) | Transferred | ddPCR | 112 | Combining KLK3, FOLH1, and NPY separates long-term responders from short-term responders with 87% sensitivity and 82% specificity |
| Panel of mRNAs | NSCLC | Detection of early- and late-stage NSCLC | Endogenous | RNA-seq | 64 | Accuracy 88%, AUC 0.94, 95% CI 0.92-0.96, P < .001 for detection of late-stage NSCLC; accuracy 81%, AUC 0.89, 95% CI 0.83-0.95, P < .001 for detection of early-stage NSCLC |
| Panel of mRNAs | NSCLC | Early detection of NSCLC | Endogenous | RNA-seq | 125 | Sensitivity 0.925, specificity 0.827, accuracy 0.889, and Matthews correlation coefficients 0.760 for detection of NSCLC |
| EGFRvIII | NSCLC | Biomarker for identification of appropriate treatment selection | Transferred | RT-PCR | 109 | EGFRvIII was detected in 1.5% of all patients analyzed |
| Panel of mRNAs | MM | Transcripts involved in platelet activation, signaling, and aggregation were upregulated in SMM/MM patient platelets compared with HD platelets | Endogenous | RNA-seq | 23 | Panel of 336 transcripts increased and 441 transcripts decreased |
| ALK rearrangement | NSCLC | Diagnosis of ALK-positive NSCLC and predictive value for ALK inhibitors treatment | Transferred | RT-PCR | 111 | Accuracy 80.3% for detection of ALK rearrangements using platelets |
| ITGA2B | NSCLC | Identification of stage I NSCLC and differentiate malignant from benign lung nodules | Endogenous | RNA-seq, qRT-PCR, and ddPCR | 91 | AUC 0.888, sensitivity 91.2%, and specificity 56.5% for detection of NSCLC by qRT-PCR |
| MAX, MTURN, HLA-B | Lung cancer | Detection of early-stage lung cancer patients and predictive response of chemotherapy treatment | Endogenous | Microarray, qRT-PCR | 117 | AUC 0.734, sensitivity of 60.6%, specificity of 81.7% for detection of lung cancer patients compared with healthy controls |
| AUC 0.787, sensitivity of 72.7%, specificity of 85.4%, for detection in early-stage lung cancer compared healthy donors | ||||||
| TIMP1 | CRC | TIMP1 is expressed at high levels in CRC patients; TIMP1 mRNA can be transferred to CRC cells and promote tumor growth in vivo and in vitro | Transferred | RNA-seq and qRT-PCR | 86 | AUC 0.9583 (95%CI, 0.9363–0.9803) |
| TPM3 | BrCa | TPM3 is present at high level in patients with BrCa; TPM3 mRNA is transferred through microvescicles and enhances cancer cell migration | Transferred | RNA-seq and qRT-PCR | 85 | AUC 0.9705 (95% CI, 0.9494-0.9823) for detection of BrCa |
| AUC 0.8404 (95% CI, 0.7566-0.9242) for detection of metastatic BrCa | ||||||
| Panel of mRNAs | Sarcoma | Diagnosis of sarcoma patients | Endogenous | RNA-seq | 126 | Accuracy of 87%, AUC 0.93 (95% CI, 0.86-1) |
AUC, area under the curve; BrCa, breast cancer; CI, confidence interval; CRC, colorectal cancer; DE, differentially expressed; GBM, glioblastoma; HBC, hepatobiliary cancer; HD, healthy donor; MM, multiple myeloma; PAAD, pancreatic adenocarcinoma; PCa, prostate cancer; RNA-seq, RNA sequencing; SMM, smoldering multiple myeloma.