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Table 1 List of known biomarkers in prediction of ovarian cancer treatment response

From: Prediction of the treatment response in ovarian cancer: a ctDNA approach

Biomarkers utility Weakness
CA125 Can be assessed in epithelial, endometrial and clear cell types in patients with clinical stage I- IV [52]. • Cannot be elevated in some ovarian cancer patients.
• Can be elevated in healthy premenopausal women during menses, in pregnancy, in nonmalignant gynecologic diseases, such as ovarian cysts, endometriosis, adenomyosis, and uterine leiomyomas, in several nonmalignant nongynecological diseases, such as peritoneal, pleural, and musculoskeletal inflammatory disorders as well as pelvic inflammatory disease, liver, and renal as well as cardiac disease and in most types of advanced adenocarcinomas, including breast, colorectal, pancreas, lung, endometrium, and cervix as false positive.
• Is not expressed in pure mucinous tumors [53].
HE4 Can be assessed in epithelial ovarian adenocarcinomas high [54]. • Can be elevated in endometrioid and clear cell histology [55].
• Cannot be detected in epithelial/ nonepithelial ovarian cancer, including sex cord stromal tumors and germ cell tumors [54]
• Overexpressed in gastric cancer, pancreatic cancer as well as occasionally in colon and hepatocellular cancer [56, 57].
Ova1 Ova1 score ≥ 5 in premenopausal women and ≤ 5 postmenopausal ones were detected, and was considered with higher risk of malignancy [58]. • Ova1 demonstrated 92.5% sensitivity, but lower specificity of 42.8% [58]
VEGF VEGF level was independently associated with shorter disease-free survival and overall survival [59]. • Can be compared with traditional biomarkers, such as CA125 and HE4 moderately [60].
• It must be combined with CA-125 and HE4 to increase the diagnostic sensitivity up to 84% in stage I [36].
• Can be elevated in various cancers, including colorectal, [61], lung [62], gastric [63], endometrial [64] and breast cancer [65].
Kallikreins Level more than 4.4 mg/L indicated poor prognosis in patients [66]. • Exhibit low sensitivity in the early detection of ovarian cancer.
• It must be combined with CA-125 for higher specificity and sensitivity [67].
Osteopontin Has a sensitivity of 83.3% in the detection of ovarian cancer [68]. • Its specificity is low.
• It must be combined with CA-125 for higher sensitivity [69].
Mesothelin Elevate in patients with ovarian cancer compared with normal healthy [70]. • Is not useful markers for early detection [71].
M-CSF Elevated levels of M-CSF1 in serum and ascites are associated with a poor prognosis [72]. Serum M-CSF appears to improve the diagnostic reliability of serum CA 125 alone [73]. • This biomarker expressed also in other cancers [74].
Bikunin Mediates suppression of tumor cell invasion and metastasis.
Low expression is associated with late-stage disease.
Low response to chemotherapy, and reduced survival time [44].
• Bikunin is present predominantly in amniotic fluid and urine of healthy individuals [75].
EphA2 Overexpression is associated with poor prognosis [45]. • EphA2 is overexpressed in many human cancers [76, 77].
Transthyretin Efficient serum marker for the diagnosis [47]. • Plasma levels, affected by acute and chronic diseases.
• Its usage must be considerate [78].
Transferrin receptor 1 Overexpression in high-grade tumor tissues [79]. • Overexpressed in several cancers [80,81,82].
B7-H4 Over expression can be used as a tumor marker with negative prognostic effect for epithelial cell ovarian cancer potential immunotherapeutic target [83]. • B7-H4 is highly expressed in various human tumors, including breast, ovarian, lung, pancreatic, gastric and urothelial cell carcinoma [84, 85].
Prostasin Overexpress in ovarian cancer patients at levels significantly higher than normal controls [50]. • Many human cancers show unusual expression of prostasin like urinary bladder, uterine, prostate, gastric and ovarian cancers [86, 87].
EGF receptor Is associated with less favorable disease outcomes [88]. • Little or no difference to survival, either as maintenance treatment after first-line chemotherapy or in association with chemotherapy in recurrent cancer [89].
  1. Abbreviations: CA125 cancer antigen 125, HE4 human epididymis secretory protein 4, VEGF vascular endothelial growth factor, M-CSF macrophage colony stimulating factor, EphA2 ephrin type-A receptor 2, B7-H4 a molecule of B7 family