TABLE 1.

Diagnostic, prognostic and therapeutic utility of circulating cell free mRNA in cancer.

Study Focus	Patient Cohort	Sample Type	Gene Target	Major Findings	Clinical significance	Reference
hTERT mRNA and EFGR mRNA in serum as biomarker for lung cancer	112 patients (98 NSCLC, 5 SCLC, 1 LCLC and 8 benign tumor) 80 controls	Serum	hTERT and EGFR	EGFR- cell survival, cell proliferation, invasion, angiogenesis, metastasis, dissemination of cancer cells hTERT- size and number of tumors, tumor marker progression	Diagnostic markers	Miura et al. (2006)
Role of ccf mRNA in plasma as tumor marker for gastric cancer; primary and recurrent	52 gastric cancer patients (40 preopretaive + 12 postoperative) 20 healthy controls	Plasma	hTERT and MUC1	hTERT and MUC1- Over expression in gastric cancer as released from neovessels in cancer tissues. Tumor derived mRNA released from tumor tissues detected in circulation in the absence of circulating tumor cells.	Diagnostic markers for primary gastric cancer at an early stage. Diagnostic markers for clinically occult recurrences after gastrectomy.	Tani et al. (2007)
Role of mRNA in breast cancer patients and their clinical outcome	129 patients	Plasma	Cyclin D1 and thymidylate synthase (TYMS/ TS)	TYMS mRNA- poor prognosis, negative progesterone receptor, advanced stage in colon cancer Cyclin D1 mRNA- Vascular evasion, oncogenic transformation, no response to therapy, shorter overall survival	TYMS mRNA-prognostic biomarker for advanced stages. Cyclin D1- prognostic biomarker for overall survival and therapy resistance.	García et al. (2008)
Extracellular tumor related mRNA in lymphoma and survival	42 diffuse large B-cell lymphomas (DLBCL) 25 follicular lymphoma (FL) 16 Hodgkin's lymphoma (HL)	Plasma	MYC, CCND2 and BCL2-unfavourable biomarkers BCL6, LMO2 and FN1-favourable biomarkers	LMO2 (LIM Domain Only 2)-prolonged survivalMYC, CCND2 (cyclin D2) and BCL2 (B-cell lymphoma 2)-poor prognosis, short survival, poor outcome and partial response (MYC mRNA), treatment resistance (MYC or BCl2) BCL6-better survival, favorable outcome,absence of unfavorable biomarkers	MYC, CCND2, BCL2, and BCL6-prognostic biomarkers MYC and BCL2-therapy resistance	Garcia et al. (2009)
hTERT mRNA as a diagnostic biomarker for hepatoma	638 patients (303 HCC, 89 chronic hepatitis, and 45 liver cirrhosis) 201 controls	Serum	hTERT	hTERT mRNA tumor size, tumor differentiation, superior to AFP (α-feto protein), AFP-L3 and DCP (des-γ-carboxy prothrombin) in diagnosis recurrence of HCC at early stage	Diagnostic biomarker	Miura et al. (2010)
hTERT mRNA as prognostic biomarker for prostate cancer	105 patients 68 healthy volunteers	Plasma	hTERT	hTERT mRNA- discriminates clinically localized and locally advanced disease, recurrence of prostate cancer, poor prognosis, tumor stage, vascular and perineural invasion, tumor size, metastasis	Diagnostic biomarker, MRD detection, prognostic biomarker for recurrence	March-Villalba et al. (2012)
BRCA1 and TS mRNA as biomarker for chemotherapy against gastric cancer	150 patients	Plasma	BReast CAncer gene (BRCA1) and Thymidylate synthase (TS)	BRCA1 mRNA- biomarker for selecting chemotherapy during disease progression monitoring of neoadjuvant and adjuvant therapy chemosensitivity TS- pemetrexed-based chemotherapy BRCA1- Docetaxel therapy	Therapeutic biomarkers	Shen et al. (2014)
CfmRNA and miRNA as biomarkers for prostate cancer	102 untreated Prostate cancer 50 disease free controls	Plasma	OR51E2, SIM2 mRNA miR-200c and miR-200b	SIM2 and OR51E2- prostate cancer development and progression, target for immunotherapy, better diagnosis than PSA test when combined with miR-200c and miR-200b, cancer diagnosis with PSA≤4 ng/mL miR-200c- bone metastasis, PSA level > 10 ng/µL, Bilateral tumor	Prognostic biomarkers	Souza et al. (2017)
Role of cfmRNA in predicting high risk prostate cancer	60 prostate cancer	Plasma	AMACR, BCL2, NKX3-1, GOLM1, OR51E2, PCA3, SIM2 and TRPM8	AMACR, GOLM1, TRPM8 and NKX3-1- overexpressed, associated with disease, aggressiveness, extracapsular extension, tumor stage, vesicular seminal invasion GOLM1, TRPM8 and NKX3-1- identification of high-risk prostate cancer with high sensitivity and specificity NKX3-1- Prostate cell differentiation, Prostate cancer initiation, (loss of function), high gradeprostate cancer (overexpression) TRPM8- cell migration and tumor progression	Diagnostic biomarkers	De Souza et al. (2020)
Role of GRP78 as biomarker for endometrial cancer	32 patients with endometrial cancer 20 healthy controls	Plasma	GRP78	GRP78- overexpressed in patients with endometrial cancer	Diagnostic marker	Aynekin et al. (2022)