Table 4 Expression of PIWI proteins in cancer compared to non-tumorous tissue and their association with clinicopathological data

PIWIL1

Colorectal cancer

Increased [147,148,149,150]

RT-qPCR [148, 150], RT-PCR [149], WB [150], IHC [147, 149, 150]

↓ [147, 149]

↑ [148, 149] / none [147]

PIWIL1 is an independent prognostic factor in patients without lymph node metastasis, but not in patients with lymph node metastasis [147]. More than two-fold higher expression of PIWIL1 mRNA in 16/46 (34.8%) of tumor tissues compared to healthy surrounding tissue [148]. PIWIL1 detected in 72/225 (32%) of tumors [147].

Pancreatic cancer

Increased [72]

IHC [72]

↓ [72]

↑ [72]

Gliomas

Increased [74, 84, 151]

RT-qPCR [74], RT-PCR [151], WB [151], IHC [84, 151]

↓ [151]

PIWIL1 expression associated with higher tumor grade [151].

Gastric cancer

Increased [74, 152, 153]

RT-qPCR [74], RT-PCR [152], IHC [74, 152, 153]

↓ [74, 153]

↑ [74] / none [153]

PIWIL1 mRNA expression associated with poor survival in patients with poorly differentiated or mixed-classification tumors and patients who underwent 5-fluorouracil-based adjuvant therapy [74].

Endometrial cancer

Increased[86]

RT-qPCR [86], IHC[86]

↑[86]

Seminoma

Increased [11] / Decreased [154]

RT-qPCR [154], RT-PCR [11]

No significant change in PIWIL1 mRNA in other germ cell testicular tumors and stromal cell testicular tumors [11, 154].

Breast cancer

Increased [155, 156] / variable expression [157]

RT-qPCR [155,156,157], WB [155, 156]

↓ [156]

↑ [155]

PIWIL1 mRNA expression associated with higher tumor grade [155].

Lung cancer (NSCLC)

Increased [13, 82, 158] / no change [159]

RT-qPCR [82, 158], RT-PCR [13, 159], WB [158, 159], IHC [159]

↓ [82]

PIWIL1 mRNA expressed in 11/71 (15.5%) of the tumor tissues and not detectable in the healthy adjacent tissue. PIWIL1 is an independent prognostic factor [82].

Hepatocellular carcinoma

Increased [160,161,162] / Not detected [96]

RT-qPCR [96, 161, 162], RT-PCR [160], WB [160, 161], IHC [160, 162]

↓ [160, 162]

↑ [160, 162]

Renal cell carcinoma

Increased [163] / Decreased [164]

RT-qPCR [164], IHC [163]

↑ [164]/↓ [163]

↓ [163]

PIWIL1 detected in 75/265 (28.3%) and 51/345 (14.8%) of tumors in two independent cohorts, no expression in adjacent tissues. PIWIL1 expression associated with higher tumor grade and worse survival [163]. PIWIL1 mRNA expression associated with lower tumor grade and higher piR-823 expression [164].

PIWIL2

Colorectal cancer

Increased [165, 166]

WB [165], IHC [165, 166]

↓ [165, 166]

↑ [165, 166] / none [166]

PIWIL2 expression associated with low degree of differentiation and perineural, but not lymphatic or venous invasion. No association with lymph node involvement and distant metastasis. PIWIL2 was not an independent prognostic factor [166].

Gliomas

Increased [167]

WB [167], IHC [167]

↓ [167]

PIWIL2 expression associated with higher tumor grade [167].

Lung cancer (NSCLC)

Increased [159] / Decreased [82]

RT-qPCR [82, 159], WB [159], IHC [159]

↓ [159]

Gastric cancer

Increased [153] / No change [74]

RT-qPCR [74], IHC [153]

↓ [153]

none [153]

PIWIL2 is not an independent prognostic factor [153].

Prostate cancer

Increased [168]

RT-qPCR [168], IHC [168]

↑ [168]

Breast cancer

Increased [12, 78, 156, 157, 169]

RT-qPCR [156, 157], WB [78, 156], IHC [12, 78, 169]

none [12, 156]

↑ [78]

PIWIL2 mRNA expression was significantly higher in 2/20 (10%) of the tissues in one of the studies [157]. PIWIL2 was higher in 334/1086 (30.7%) of the tissues in another study [78].

Soft tissue sarcoma

Increased [170]

RT-qPCR [170]

↑ [170]

High PIWIL2 mRNA expression associated with high PIWIL4 mRNA expression. No association with PIWIL3 [170].

Cervical cancer

Increased [94, 171]

WB [94], IHC [94, 171]

Hepatocellular carcinoma

Increased [96]

RT-qPCR [96]

Seminoma

Increased [172] / Decreased [154]

RT-qPCR [154], RNA microarray [172]

No change or decrease in PIWIL2 mRNA expression in non-seminoma testicular tumors [154, 172].

Renal cell carcinoma

No change [164]

RT-qPCR [164]

↑ [164]

PIWIL2 mRNA associated with lower tumor grade [164].

Non-melanoma skin cancer

No change [173]

IHC [173]

Concordant results in basal cell and squamous cell carcinomas [173].

Bladder cancer

Not detected [14]

RT-qPCR [14]

PIWIL3

Gastric cancer

Increased [153, 174] / No change [74]

RT-qPCR [74, 174], IHC [153]

none [153]

↑ [174] / none [153, 174]

PIWIL3 mRNA expression associated with presence of lymph node metastasis in diffuse-type but not in intestinal-type gastric cancer [174].

Soft tissue sarcoma

Increased [170]

RT-qPCR [170]

none [170]

Renal cell carcinoma

No change [164]

RT-qPCR [164]

none [164]

Lung cancer (NSCLC)

Increased [82] / No change [159]

RT-qPCR [82, 159], WB [159], IHC [159]

PIWIL3 mRNA detected in 5/71 (7%) of the tumor tissues, no expression in healthy adjacent tissue [82].

Breast cancer

No change [156]

RT-qPCR [156], WB [156]

Hepatocellular carcinoma

No change [96]

RT-qPCR [96]

Gliomas

Decreased [118]

WB [118]

PIWIL3 expression associated with lower tumor grade [118].

Seminoma

Decreased [154]

RT-qPCR [154]

PIWIL4

Soft tissue sarcoma

Increased [170]

RT-qPCR [170]

↑ [170]

High PIWIL4 mRNA expression associated with high PIWIL2 mRNA expression. No association with PIWIL3 [170].

Gastric cancer

Increased [153] / No change [74]

RT-qPCR [74], IHC [153]

none [153]

↑ [153]

Cervical cancer

Increased [175]

RT-qPCR [175]

Hepatocellular carcinoma

Increased [96]

RT-qPCR [96]

PIWIL4 mRNA expression not associated with piR-Hep1 expression [96].

Breast cancer

Increased [157] / no change [156]

RT-qPCR [156, 157], WB [156]

Renal cell carcinoma

No change [164]

RT-qPCR [164]

↑ [164]

PIWIL4 mRNA expression associated with lower tumor grade [164].

Lung cancer (NSCLC)

No change [159] / Decreased [82]

RT-qPCR [82, 159], WB [159], IHC [159]

↑ [82]

Seminoma

Decreased [154]

RT-qPCR [154]

Decrease in PIWIL4 mRNA expression in non-seminoma testicular tumors [154].