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Bibi et al. J Transl Genet Genom 2024;8:119-161 https://dx.doi.org/10.20517/jtgg.2023.50 Page 127

can be improved for better quality or accuracy through IHC to find mismatch repair-related proteins,
microsatellite instability analysis, and next-generation sequencing. Despite the rarity of this kind of event, it
has therapeutic value. Additionally, a study found that bladder cancer subjects with DNA mismatch repair
deficiency/microsatellite instability genotypes have a favorable prognosis for anti-PD-1/PD-L1
therapy [135-138] .

Prostein
Prostein is a transmembrane protein that is commonly produced in both healthy and cancerous prostate
tissues and may play a role in prostate cancer cell invasion and migration. Our research indicates that 87%
of the primary tumors have maintained or even raised transcript levels compared to autologous non-
malignant tissue samples. When compared to cancers that are not organ-confined, prostein expression is
notably higher in prostate cancer [138-142] . Researchers have discovered a peptide derived from prostein and
presented by HLA-A*0201, which activates tumor-reactive cytotoxic T lymphocytes (CTLs) when CD8+ T
cells are stimulated In vitro with dendritic cells filled with the peptide, and also found immunogenic T-cell
epitopes, such as HLA-Cw*0501 and HLA-B*5101 [111,140,143] .

According to findings by Wolfgang et al., prostein is not detectable in non-prostatic glands but can be identified
using immunohistochemical (IHC) methods in acinar, intra-ductal prostate-gland adenocarcinomas .
[144]

T-cell receptor gamma alternate reading frame protein
The non-rearranged T-cell receptor gamma-chain locus has a unique androgen-regulated gene that gives
rise to T-cell receptor gamma alternate reading frame protein (TARP). Mitochondria of PCa in men exhibit
TARP. Females with breast cancer can be identified by TARP [145,146] . Researchers discovered that androgen
upregulated TARP in the mitochondria of prostate cell lines using subcellular fractionation,
immunocytochemistry, and Western blot analysis. Immunohistochemistry and mitochondrial fractionation
data suggested that TARP was present in the outer mitochondrial membrane and that it might interact with
[147]
mitochondria to carry out its biological activity .

In vitro prostate and breast cancer cell-reactive cytotoxic T lymphocytes are activated by a number of
naturally occurring HLA-A*0201-restricted TARP peptides. Additionally, 2HLA class-II binding amino acid
residues generated with TARP have been demonstrated to trigger efficient CD4+ T cell responses [148-150] . In
order to evaluate TARP for both therapeutic and diagnostic purposes, a new targeted strategy using
antibodies that bind each HLA class-I peptide group on tumor cell surfaces.

The possibility of incorrect matching between the exogenous, endogenous T-cell receptor and T-cell
receptor chains is a significant drawback of employing TCR-engineered T cells. TCRs reactive against self-
antigens and TCRs with unexpected specificity could result from mispairing, which would produce
autoreactive T cells. Additionally, incorrectly paired transferred TCRs may compete with one another for
CD3, lowering the level of surface expression. There are a number of methods to prevent mispairing, such
as murinizing human TCRs to give them a comparative benefit for the interaction of CD3 [151-155] .

Transient receptor potential melastatin 8
Transient receptor potential melastatin 8 (TRPM8) is a calcium channel amino acid that is encoded by gene
TRPM8 and activated by cold temperatures, menthol, and other substances . TRPM8 is primarily
[156]
expressed in sensory neurons, which are responsible for mediating the cold sensation . Additionally,
[157]
TRPM8 is also expressed in non-neuronal organs, such as the prostate gland . Androgens, the male sex
[158]
hormones that increase the growth and functionality of the prostate, control TRPM8 expression inside the