Table 3.

Potential biomarkers for PGCCs.

References	Potential Biomarkers	Type of Tumor
Herbein [213], Song et al. [214], and Zhang et al. [215]	Myc, PI3K, Akt, p53, Rb, and IL-6—elevated Myc expression, activation of the PI3K/Akt pathway, repression of p53 and Rb genes, and loss of Rb leading to increased IL-6 production, correlating with the appearance of PGCCs.	Cancer in general
	CD44, CD133, OCT4, SOX2, and Nanog—high expression in PGCCs reveals the potential for multidifferentiation and self-renewal capacity similar to embryonic stem cells, with such expression pattern transmissible to the produced diploid descendant cells.
	S100A4—expression is correlated with the invasive and metastatic ability of PGCCs and their progeny cells.
	ZEB1—increased expression in prostate cancer PGCCs.
	Twist, Slug, and Snail—expression buildup in colon cancer PGCCs.
	N-cadherin, vimentin, and cathepsin—increased expression in PGCCs of some cancer cell lines.
	SPO11 and Mos-kinase—meiotic and telomere-related mechanisms may play a role in PGCC neosis.
	ASAH1—elevated expression in radiation-induced PGCC in prostate cancer and lung cancer.
	AURK—correlated with induction of polyploid cells by regulating mitosis or the arrest of cell division.
	CSC, CD44, and CD133—expression of markers of stem cell properties in PGCCs.
	GCM1/syncytin-1—highlight the presence of cell fusion during the formation of PGCCs.
El Baba et al. [216] and Nehme et al. [217]	Ki67—a proliferative index marker, which is also strongly linked to tumor initiation, growth, and metastasis, able to evaluate the proliferation of PGCCs that acquired embryonic-like stemness and a hybrid epithelial–mesenchymal phenotype.	Breast cancer
	EZH2, SUZ12, and Myc—PGCCs show an overexpression of these proteins.
	Ki67, Vimentin, CD49f, CD44, CD24, OCT4, NANOG, and E-cadherin—call attention to the high expression when associated with PGCCs.
	EpCAM—highlighted a downregulation in PGCCs.
Liu et al. [218] and Liu et al. [219]	CDC25C—Regulation of its expression and subcellular localization correlates with the formation of PGCCs by activating cyclin B1–CDK1.	Breast and ovarian cancer
	p38MAPK-ERK-JNK—Cell cycle progression and formation of PGCCs by regulation of CDC25C.
Tagal and Roth [220] and Zhang et al. [221]	Aurora A and B—Inhibition induces PGCC formation.	Breast and lung cancer
Bowers et al. [222], Niu et al. [223], Silva et al. [224], and Yart et al. [225]	p21—marks a temporary arrest in the cell cycle of PGCCs similar to senescence.	Ovarian cancer
	LCB-II and p62/SQSTM1—autophagy markers with increased levels, but a low autophagic flow for PGCCs is highlighted, while their derived progeny has high rates of autophagy during neosis.
	TNF-α, NF-κB, lipopolysaccharide (LPS), and IL-6—more regulated in PGCCs, while pathways related to cell proliferation and division were inhibited. IL-6 facilitates PGCC formation and embryonic stem acquisition via an autocrine loop. PGCCs can use IL-6 protein as a paracrine mechanism to facilitate the transformation of fibroblasts into more tumor-promoting CAFs for chemoresistance.
	PAX 8, WT-1, Ki-67, ER, and p53—positive and aberrant expression (overexpression) correlated with the presence of PGCCs.
	GRP78—its overexpression is correlated with the UPR (unfolded protein response) activation marker aspect. UPR induces ovarian cancer cell fusion and the formation of PGCCs.
Thura et al. [226]	PRL3—induces the formation of PGCCs that express markers of embryonic stem cells, such as SOX2 and OCT4.	Ovarian cancer, melanoma and stomach cancer
Fu et al. [227], Li et al. [228], Peerpen et al. [229], and Zhao et al. [230]	PLK4—kinase overexpressed in PGCCs, and descendant cells showed strong migration and invasion abilities. Its interaction with CDC25C is associated with the formation of PGCCs.	Colorectal cancer
	GCM1, Syncytin-1, ASCT-2, OCT-4, NANOG, CD44, and CD133—correlated with the formation of PGCCs via GCM1-mediated cell fusion, regulating syncytin-1 expression, and generating offspring expressing embryonic stem cell markers, including and with increased expression of epithelial-to-mesenchymal transition (EMT) markers.
	ARID1A—its inhibition correlated with the increase in PGCCs and multicellular spheroids.
	S100A10, CD44, and CD133—correlated with expression and nuclear localization, modified by SUMOylation, with high proliferation and migration of PGCCs and their daughter cells (with stem cell properties), and with differentiation, metastases, and recurrences by regulation of the expression of ARHGEF18, PTPRN2, and DEFA3.
Liu et al. [231] and You et al. [232]	Cyclin B1, CDC25C, CDK1, E-cadherin, and EIF-4A—demonstrated lower expression in PGCCs when compared to normal cancer cells.	Head and neck cancer
	Vimentin and CD133—demonstrated increased expression in PGCCs.
	RIPK1—its overexpression was induced through the AMPK-mTOR pathway, which promoted the formation of PGCCs upon analysis of the transcriptional and epigenetic landscape of these cells.
Lu et al. [233] and White-Gilbertson et al. [234]	ASAH1—interferes with generation of PGCC offspring.	Melanoma and prostate cancer
	p53—inhibition promotes generation of PGCC.
	INSIG1—has lower expression in PGCCs and acts by negatively regulating cholesterol metabolism.
	SR-B1—is a type 1 class B scavenger receptor that presents high levels of expression in PGCCs.
Pustovalova et al. [235]	p53, OCT4 (low expression), NANOG (low expression), CD44 (present expression), CD133 (present expression), and p21—ionizing radiation influences the expression and accumulation of these proteins in a quiescent state (dormancy) and spontaneous formation of PGCCs with or without slow cycling, followed by re-entry into the cell cycle and formation of therapy-resistant clones with increased migratory and invasive activity.	Lung cancer
Voelkel-Johnson [236]	YAP—associated with ASAH1 promotes the formation of PGCC progeny.	Liver cancer

PGCCs: polyploid giant cancer cells; ER: estrogen receptor.