Biomarkers in endometriosis: challenges and opportunities

In the paper

“MicroRNA expression in normal endometrium exhibits dynamic changes across the menstrual cycle (105), where their involvement in nonpathologic mechanisms can be used to understand physiologic systems that have derailed into pathologic phenotypes.”

What the sources say

• Supported

  The Introduction reports that several studies found fluctuations in endometrial miRNA profiles across the menstrual cycle. The Discussion likewise describes differential expression in receptive and non-receptive endometrium. The paper’s finding of no significant change concerns circulating plasma miRNAs, not endometrial tissue. (LLM, conf=0.93)

  cites [105] Rekker, 2013, Circulating microRNA profile throughout the menstrual cycle, PLoS One source

In the paper

“In addition, Wang et al. (2016) showed that a combination of five lncRNAs can differentiate patients from disease-free control subjects with 89.7% sensitivity and 73.2% specificity, further demonstrating the potential of circulating lncRNA as a noninvasive diagnostic biomarker for endometriosis (112).”

What the sources say

• Supported

  The Results section, “Investigation of circulating lncRNAs for use in the diagnosis of endometriosis,” reports 89.66% sensitivity and 73.17% specificity for the five-lncRNA combination, matching the citing sentence after rounding. The Discussion identifies those circulating lncRNAs as potential non-invasive biomarkers for endometriosis. (LLM, conf=0.95)

  cites [112] Wang, 2016, Genome-wide long noncoding RNA analysis identified circulating lncRNAs as novel noninvasive diagnostic biomarkers for gynecological disease, Sci Rep source

In the paper

“They further identified 1,557 lncRNAs specific to the serum and 1,310 lncRNAs specific to the endometriotic tissues of endometriosis patients (112), demonstrating that the function of lncRNAs in serum may be different from that of lncRNAs found in tissue, echoing a similar pattern found in miRNA expression patterns in serum and tissue.”

What the sources say

• Supported

  The Results section on differential expression between tissue and serum explicitly says that the expression pattern and function of serum lncRNAs may differ from those in tissue. The same section reports 1,557 lncRNAs present only in the serum set and 1,310 present only in the endometriosis tissue set. (LLM, conf=0.95)

  cites [112] Wang, 2016, Genome-wide long noncoding RNA analysis identified circulating lncRNAs as novel noninvasive diagnostic biomarkers for gynecological disease, Sci Rep source

In the paper

“For decades, both basic and clinical research have been much focused on elucidating the pathogenesis of endometriosis, but they have lumped different phenotypes of the disease, including ovarian, peritoneal, and deep infiltrating endometriosis, as one entity.”

In the paper

“which have demonstrated that the endometrium of endometriosis patients displays aberrant molecular expression patterns that give it the ability to implant, invade, and develop into endometriotic foci (27)(28)(29)(30).”

What the sources say

• Not checked yetcites [27] Burney, 2007, Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis, Endocrinology source
• Not checked yetcites [28] Bulun, 2006, Progesterone resistance in endometriosis: link to failure to metabolize estradiol, Mol Cell Endocrinol source
• Not checked yetcites [29] Mehasseb, 2011, Estrogen and progesterone receptor isoform distribution through the menstrual cycle in uteri with and without adenomyosis, Fertil Steril source

In the paper

“For example, Naqvi et al. (26) observed five hypermethylated (MGMT, DUSP22, CDCA2, ID2, and RBBP7) and five hypomethylated (TNFRSF1B, MBPR1B, ZNF681, IGSF21, and TP73) genes in eutopic endometrium of patients compared with endometriosis-free control subjects.”

What the sources say

• Not checked yetcites [26] Naqvi, 2014, Altered genome-wide methylation in endometriosis, Reprod Sci source

In the paper

“Such heterogeneity of disease phenotype also increases the potential of false-negative laparoscopic surgery in symptomatic women, wherein a ''clean'' pelvic cavity might not necessarily indicate the absence of endometriosis in other areas of the body (Table 1).”

In the paper

“Unless accompanied by explorative laparoscopic surgery for complete diagnosis, accurate differential diagnosis in potential endometriosis patients based on symptoms proves to be a difficult challenge.”

In the paper

“The concentration of peripheral markers in blood and peritoneal fluid may be diluted with factors that are driving the development of conditions other than endometriosis in patients.”

In the paper

“Case studies have shown that symptoms of pelvic pain are not a useful diagnostic parameter to differentiate women with or without endometriosis (54), owing to the similarity of symptoms with other pelvic pain pathologies, such as irritable bowel disease.”

What the sources say

• Not checked yetcites [54] Ballard, 2010, Can specific pain symptoms help in the diagnosis of endometriosis? A cohort study of women with chronic pelvic pain, Fertil Steril source

In the paper

“It is highly likely, however, that the altered endometrial response was due to transitory modification in the genome imposed by the external presence of ectopic foci (9).”

What the sources say

• Not checked yetcites [9] Guo, 2009, Epigenetics of endometriosis, Mol Hum Reprod source

In the paper

“These conditions may also have underlying immunologic and inflammatory pathologic mechanisms with peripheral increase in cytokines commonly associated with endometriosis, thereby potentially introducing bias in studies using peripheral cytokines as diagnostic indicators of endometriosis.”

In the paper

“Owing to ethical constraints, it is unlikely that we will be able to study the early stages of endometriosis development by injecting menstrual fragments into the peritoneal cavity of women.”

In the paper

“These results suggest that women with incidental findings of endometriosis who do not suffer from typical symptoms of endometriosis perhaps have higher tolerance to pain.”

In the paper

“Indeed, asymptomatic endometriosis (55,56), which is the incidental finding of endometriotic foci during other laparoscopic surgeries, such as tubal ligation (46,57), complicates our understanding of the relationship between the presence of endometriotic foci and incidence of pelvic pain in symptomatic women.”

What the sources say

• Not checked yetcites [55] Rawson, 1991, Prevalence of endometriosis in asymptomatic women, J Reprod Med
• Not checked yetcites [56] Thomas, 1996, The relevance of asymptomatic endometriosis, Hum Reprod source
• Not checked yetcites [46] Faske, 2012, Incidental finding of decidualized vesical endometriosis in an asymptomatic obstetrical patient, J Ultrasound Med source

In the paper

“The ability of endometriosis to be found not only in the abdominopelvic cavity, but also in the thoracic cavity and even in nasal mucosa is an example that mechanisms aside from retrograde menstruation are involved in the pathogenesis of endometriosis.”

In the paper

“Those studies hint at the ''cross-talk'' between the ectopic endometriotic foci and the eutopic endometrium, wherein the presence of endometriosis likely programs hyperestrogen responsiveness and progesterone resistance into the eutopic endometrium as disease progresses (98) (Fig. 1).”

What the sources say

• Not checked yetcites [98] Afshar, 2013, Changes in eutopic endometrial gene expression during the progression of experimental endometriosis in the baboon, Papio anubis, Biol Reprod source

In the paper

“Using nonhuman primate models of endometriosis, it has been demonstrated that it is the presence of the menstrual fragments in the peritoneal cavity that directly influences gene expression pattern of the eutopic endometrium (97,98).”

What the sources say

• Not checked yetcites [97] Gashaw, 2006, Induced endometriosis in the baboon (Papio anubis) increases the expression of the proangiogenic factor CYR61 (CCN1) in eutopic and ectopic endometria, Biol Reprod source
• Not checked yetcites [98] Afshar, 2013, Changes in eutopic endometrial gene expression during the progression of experimental endometriosis in the baboon, Papio anubis, Biol Reprod source

In the paper

“Interestingly, functional neuroanatomic studies using magnetic resonance imaging have demonstrated that women with symptomatic endometriosis display hypersensitivity to pain owing to increased neuronal connectivity in areas of central pain perception (59).”

What the sources say

• Not checked yetcites [59] Brawn, 2014, Central changes associated with chronic pelvic pain and endometriosis, Hum Reprod Update source

In the paper

“Also, pelvic pain is not present in all endometriosis patients.”

What the sources say

• Not checked yetcites [55] Rawson, 1991, Prevalence of endometriosis in asymptomatic women, J Reprod Med
• Not checked yetcites [56] Thomas, 1996, The relevance of asymptomatic endometriosis, Hum Reprod source

In the paper

“A major limitation to using what we know to be molecularly different in endometrium of endometriosis patients as biomarkers is the overlap of similar findings in other gynecologic disorders.”

In the paper

“Currently, the use of DNA methylation pattern of the eutopic endometrium as a minimally invasive diagnostic biomarker for endometriosis seems to be, unfortunately, ineffective and not useful in predicting disease risk (101).”

What the sources say

• Not checked yetcites [101] Pagliardini, 2015, Replication and meta-analysis of previous genome-wide association studies confirm vezatin as the locus with the strongest evidence for association with endometriosis, Hum Reprod source

In the paper

“Already, findings by Saare et al. discourage the use of endometrial DNA methylome as biomarkers for endometriosis, because significant methylation pattern differences in the endometrium were not found that could discriminate patients from healthy women with acceptable sensitivity and specificity (82).”

What the sources say

• Not checked yetcites [82] Saare, 2016, The influence of menstrual cycle and endometriosis on endometrial methylome, Clin Epigenetics source

In the paper

“Noninvasive biomarkers with high specificity and sensitivity will be a challenge for endometriosis, not only because of heterogeneity of disease characteristics, but also because of comorbidities suffered by endometriosis patients.”

In the paper

“In accordance with numerous studies demonstrating progesterone resistance in the endometrium of patients in secretory phase, they also found the greatest differences in methylation patterns between the endometrium of patients and from control subjects in the midsecretory phase of menstrual cycle (100), further confirming molecular abnormalities apparent in eutopic endometrium of women with endomet”

What the sources say

• Not checked yetcites [100] Houshdaran, 2016, Aberrant endometrial DNA methylome and associated gene expression in endometriosis, Biol Reprod source

In the paper

“Furthermore, aberrant responsiveness to ovarian hormones is not a feature unique to endometriosis alone, but also shared with adenomyosis, a disease where endometrial tissue is found within the myometrium.”

In the paper

“These potential confounding factors hinder our progress of noninvasive biomarker discovery because they affect the analysis of scientific findings.”

In the paper

“As thoroughly reviewed by Guo et al. (9), the eutopic endometrium displays aberrant molecular regulatory mechanisms due to epigenetic changes in steroid hormone-responsive genes.”

What the sources say

• Not checked yetcites [9] Guo, 2009, Epigenetics of endometriosis, Mol Hum Reprod source

In the paper

“Equally important is the characteristic progesterone resistance of eutopic endometrium in women with moderate to severe endometriosis, where the unresponsiveness to progesterone results in incomplete transition of the endometrium from proliferative to early secretory phase of uterine cycle (85).”

What the sources say

• Not checked yetcites [85] Burney, 2009, MicroRNA expression profiling of eutopic secretory endometrium in women with versus without endometriosis, Mol Hum Reprod source

In the paper

“Indeed, similar gene expression patterns between women with endometriosis and other pelvic/ uterine pathology (adenomyosis, uterine prolapse, and uterine fibroids) were also observed by Tamaresis et al., which suggested that the gene expression pattern of endometrium might be similarly perturbed across women with different pelvic pathologies (93).”

What the sources say

• Not checked yetcites [93] Tamaresis, 2014, Molecular classification of endometriosis and disease stage using high-dimensional genomic data, Endocrinology source

In the paper

“It is important to emphasize that the endometrium of women with endometriosis has been documented to respond differently to ovarian hormones (83-86), and we can use this fact to discover new potential biomarkers through minimally invasive means (87).”

What the sources say

• Not checked yetcites [83] Gui, 1999, Regulation of HOXA-10 and its expression in normal and abnormal endometrium, Mol Hum Reprod source
• Not checked yetcites [84] Kim, 2007, Altered expression of HOXA10 in endometriosis: potential role in decidualization, Mol Hum Reprod source
• Not checked yetcites [85] Burney, 2009, MicroRNA expression profiling of eutopic secretory endometrium in women with versus without endometriosis, Mol Hum Reprod source

In the paper

“Furthermore, Wessels et al. demonstrated the effectiveness of plasma brain-derived neurotropic factor as a noninvasive biomarker for detecting patients with stage I-II endometriosis with 91.7% sensitivity and 69.4% specificity (78).”

What the sources say

• Not checked yetcites [78] Wessels, 2016, Assessing brain-derived neurotrophic factor as a novel clinical marker of endometriosis, Fertil Steril source

In the paper

“Indeed, it will be a daunting task to develop a specific set of diagnostic biomarkers that is capable in differentiating different types and degrees of endometriosis in suspected women based on symptomatology alone (14).”

What the sources say

• Not checked yetcites [14] Vercellini, 2007, Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients, Hum Reprod source

In the paper

“A meta-analysis of eight GWASs published to date (24) demonstrated SNPs in six genetic loci, including 7p15.2,WNT4, VEZT, CDKN2B-AS1, ID4, and GREB1 across European, American, and Japanese women with stage III-IV endometriosis.”

What the sources say

• Not checked yetcites [24] Rahmioglu, 2014, Genetic variants underlying risk of endometriosis: Insights from meta-analysis of eight genome-wide association and replication datasets, Hum Reprod Update source

In the paper

“This is critical to elucidate why only 10% of women develop endometriosis although the phenomenon of retrograde menstruation occurs in 76%-90% of reproductive-age women (94)(95)(96).”

What the sources say

• Not checked yetcites [94] Halme, 1984, Retrograde menstruation in healthy women and in patients with endometriosis, Obstet Gynecol
• Not checked yetcites [95] Liu, 1986, Endometriosis: its association with retrograde menstruation, dysmenorrhoea and tubal pathology, Br J Obstet Gynaecol source
• Not checked yetcites [96] Blumenkrantz, 1981, Retrograde menstruation in women undergoing chronic peritoneal dialysis, Obstet Gynecol

In the paper

“Furthermore, Jia et al. demonstrated the applicability of the circulating level of miR-17-5p, miR-20a, and miR-22 in discriminating patients with severe endometriosis from control cohorts with an area under the curve value of 0.90 (110), further verifying the potential use of circulating miRNA as a diagnostic marker for endometriosis.”

What the sources say

• Not checked yetcites [110] Jia, 2013, Plasma miR-17-5p, miR-20a and miR-22 are down-regulated in women with endometriosis, Hum Reprod source

In the paper

“This inappropriate selection of control led to their inability to discriminate endometriosis patients from others with nonendometriosisrelated pelvic inflammation and pain (115), effectively demonstrating that proinflammatory cytokines may not be suitable candidates for a noninvasive biomarker for endometriosis, unless proper control subjects can be established.”

What the sources say

• Not checked yetcites [115] Vodolazkaia, 2012, Evaluation of a panel of 28 biomarkers for the noninvasive diagnosis of endometriosis, Hum Reprod source

In the paper

“Burney et al., based on their previous transcriptomics analysis (27) and with the use of computational analysis, discovered a potential functional relationship between decreased expression of miR-9 and miR-34 families in early secretoryphase eutopic endometrium of patients and their role in the delayed transition from proliferative to secretory phase in women with severe endometriosis (85).”

What the sources say

• Not checked yetcites [27] Burney, 2007, Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis, Endocrinology source
• Not checked yetcites [85] Burney, 2009, MicroRNA expression profiling of eutopic secretory endometrium in women with versus without endometriosis, Mol Hum Reprod source

In the paper

“This inappropriate selection of control led to their inability to discriminate endometriosis patients from others with nonendometriosisrelated pelvic inflammation and pain (115), effectively demonstrating that proinflammatory cytokines may not be suitable candidates for a noninvasive biomarker for endometriosis, unless proper control subjects can be established.”

What the sources say

• Not checked yetcites [115] Vodolazkaia, 2012, Evaluation of a panel of 28 biomarkers for the noninvasive diagnosis of endometriosis, Hum Reprod source

In the paper

“In addition, Wang et al. (2016) showed that a combination of five lncRNAs can differentiate patients from disease-free control subjects with 89.7% sensitivity and 73.2% specificity, further demonstrating the potential of circulating lncRNA as a noninvasive diagnostic biomarker for endometriosis (112).”

What the sources say

• Not checked yetcites [112] Wang, 2016, Genome-wide long noncoding RNA analysis identified circulating lncRNAs as novel noninvasive diagnostic biomarkers for gynecological disease, Sci Rep source

In the paper

“In addition, Joshi et al. recently demonstrated, in a nonhuman primate model of endometriosis, the functional implication of increased expression of miR-29c in endometrial progesterone resistance (108).”

What the sources say

• Not checked yetcites [108] Joshi, 2016, Progesterone resistance in endometriosis is modulated by the altered expression of microRNA-29c and FKBP4, J Clin Endocrinol Metab source

In the paper

“Using genome-wide microarray approach, Wang et al. in 2015 (113) found 1,277 lncRNAs that were dysregulated in the secretory-phase eutopic endometrium of patients compared with the menstrual-phase-matched endometrium from a control cohort.”

What the sources say

• Not checked yetcites [113] Wang, 2015, Genome-wide microarray analysis of long noncoding RNAs in eutopic secretory endometrium with endometriosis, Cell Physiol Biochem source

In the paper

“As cautioned by Hull and Nisenblat, and echoed by the conclusions from Cochrane Database of Systematic Reviews, the interpretation of data can not be hindered by the heterogeneity of study designs, where the results apply only to the cohort of patients and control subjects selected for that study (87).”

What the sources say

• Not checked yetcites [87] Louise Hull, 2013, Tissue and circulating microRNA influence reproductive function in endometrial disease, Reprod Biomed Online source

In the paper

“Mihalyi et al. showed the possibility of diagnosing minimal to mild endometriosis with the use of a combination of cytokines (interleukin [IL] 6, IL-8, tumor necrosis factor [TNF] a, cancer antigen [CA] 125, CA-19-9, and high-sensitivity C-reactive protein) with 60%-71% specificity and 87%-92% sensitivity (114).”

What the sources say

• Not checked yetcites [114] Mihalyi, 2010, Noninvasive diagnosis of endometriosis based on a combined analysis of six plasma biomarkers, Hum Reprod source

In the paper

“For example, despite finding significant methylation differences in CpG islands in the secretory phase of the menstrual cycle when endometrium samples are compared by disease (with or without endometriosis), the methylation patterns between disease and control were not simply robust to be useful as diagnostic biomarkers independently from menstrual cycle (82,100,104).”

What the sources say

• Not checked yetcites [82] Saare, 2016, The influence of menstrual cycle and endometriosis on endometrial methylome, Clin Epigenetics source
• Not checked yetcites [100] Houshdaran, 2016, Aberrant endometrial DNA methylome and associated gene expression in endometriosis, Biol Reprod source
• Not checked yetcites [104] Yamagata, 2014, Genome-wide DNA methylation profiling in cultured eutopic and ectopic endometrial stromal cells, PLoS One source

In the paper

“Indeed, there is merit for the circulating and tissue miRNA to be used as noninvasive or minimally invasive biomarkers for endometriosis, especially for severe cases of endometriosis (110).”

What the sources say

• Not checked yetcites [110] Jia, 2013, Plasma miR-17-5p, miR-20a and miR-22 are down-regulated in women with endometriosis, Hum Reprod source

In the paper

“They further identified 1,557 lncRNAs specific to the serum and 1,310 lncRNAs specific to the endometriotic tissues of endometriosis patients (112), demonstrating that the function of lncRNAs in serum may be different from that of lncRNAs found in tissue, echoing a similar pattern found in miRNA expression patterns in serum and tissue.”

What the sources say

• Not checked yetcites [112] Wang, 2016, Genome-wide long noncoding RNA analysis identified circulating lncRNAs as novel noninvasive diagnostic biomarkers for gynecological disease, Sci Rep source

In the paper

“Owing to an increase in incidence of early menarche in young girls displaying endometriosis-related symptoms at an earlier age (12), the need to identify this cohort by means of a reliable diagnostic marker is imperative.”

What the sources say

• Not checked yetcites [12] Ballweg, 2004, Impact of endometriosis on women’s health: comparative historical data show that the earlier the onset, the more severe the disease, Best Pract Res Clin Obstet Gynaecol source

In the paper

“Wang et al. in 2016 (112), using a larger cohort of samples from serum and tissue, identified 1,682 and 1,435 lncRNAs with dysregulated expression in the serum and ectopic endometriotic tissues, respectively, of patients (112).”

What the sources say

• Not checked yetcites [112] Wang, 2016, Genome-wide long noncoding RNA analysis identified circulating lncRNAs as novel noninvasive diagnostic biomarkers for gynecological disease, Sci Rep source

In the paper

“Wang et al. (2016) further analyzed the serum samples accounting for different stages of endometriosis and found the expression level of one lncRNA-ENST00000482343-to be correlated with disease progression, suggesting the potential usefulness of the expression pattern of lncRNA in detecting the severity of disease (112).”

What the sources say

• Not checked yetcites [112] Wang, 2016, Genome-wide long noncoding RNA analysis identified circulating lncRNAs as novel noninvasive diagnostic biomarkers for gynecological disease, Sci Rep source

In the paper

“Chronic inflammation induced by the ectopic presence of endometrial fragments (damage-associated molecular patterns [DAMPs]) lead to potential epigenetic modification programming within the eutopic endometrium.”

• Also stated in: § CONCLUSION · plain

  “This shows that endometriosis is indeed a chronic inflammatory disease wherein the sterile inflammation induced by the cyclic deposition of menstrual fragments can lead to pathogenic epigenetic changes in the eutopic endometrium.”

What the sources say

• Not checked yetcites [97] Gashaw, 2006, Induced endometriosis in the baboon (Papio anubis) increases the expression of the proangiogenic factor CYR61 (CCN1) in eutopic and ectopic endometria, Biol Reprod source

In the paper

“Furthermore, there seems to be a discrepancy between the level of miRNA expression in tissues (111) and in blood (109).”

What the sources say

• Not checked yetcites [111] Petracco, 2011, MicroRNA 135 regulates HOXA10 expression in endometriosis, J Clin Endocrinol Metab source
• Not checked yetcites [109] Cho, 2015, Circulating microRNAs as potential biomarkers for endometriosis, Fertil Steril source

In the paper

“Cho et al. showed that the circulating level of let-7b can be used as a reliable biomarker with 83.3% sensitivity and 100% specificity in diagnosis of endometriosis (109).”

What the sources say

• Not checked yetcites [109] Cho, 2015, Circulating microRNAs as potential biomarkers for endometriosis, Fertil Steril source

In the paper

“Aberrant regulation of gene transcription and post-translational regulatory mechanisms through noncoding RNAs likely contribute to development of progesterone resistance and heightened response to estrogen, which are two key characteristics of the eutopic endometrium of women with endometriosis.”

In the paper

“They further identified 1,557 lncRNAs specific to the serum and 1,310 lncRNAs specific to the endometriotic tissues of endometriosis patients (112), demonstrating that the function of lncRNAs in serum may be different from that of lncRNAs found in tissue, echoing a similar pattern found in miRNA expression patterns in serum and tissue.”

What the sources say

• Not checked yetcites [112] Wang, 2016, Genome-wide long noncoding RNA analysis identified circulating lncRNAs as novel noninvasive diagnostic biomarkers for gynecological disease, Sci Rep source

In the paper

“Of particular relevance is the significance of the fact that the initial presence of the ectopic foci can influence the gene expression pattern of the eutopic endometrium with disease progression (97).”

What the sources say

• Not checked yetcites [97] Gashaw, 2006, Induced endometriosis in the baboon (Papio anubis) increases the expression of the proangiogenic factor CYR61 (CCN1) in eutopic and ectopic endometria, Biol Reprod source

In the paper

“This shows that endometriosis is indeed a chronic inflammatory disease wherein the sterile inflammation induced by the cyclic deposition of menstrual fragments can lead to pathogenic epigenetic changes in the eutopic endometrium.”

What the sources say

• Not checked yetcites [97] Gashaw, 2006, Induced endometriosis in the baboon (Papio anubis) increases the expression of the proangiogenic factor CYR61 (CCN1) in eutopic and ectopic endometria, Biol Reprod source

In the paper

“It is more likely that instead of a single biomarker, a group of biomarkers will provide improved diagnostic performance and minimize false positives and negatives during differential diagnosis.”

In the paper

“As a transcriptional regulator, it is likely that aberrant expression of miRNA translates to dysregulated gene expression in the eutopic endometrium of patients.”

In the paper

“Interestingly, though, they found increased levels of proinflammatory markers, including TNF-a, IL-6, and IL-1b, in the control group rather than the endometriosis group in the training data set, remarking on the possibility of nonendometriotic pelvic pathology contributing to the increase in the control group of women.”

What the sources say

• Not checked yetcites [115] Vodolazkaia, 2012, Evaluation of a panel of 28 biomarkers for the noninvasive diagnosis of endometriosis, Hum Reprod source

In the paper

“Wang et al. in 2016 (112), using a larger cohort of samples from serum and tissue, identified 1,682 and 1,435 lncRNAs with dysregulated expression in the serum and ectopic endometriotic tissues, respectively, of patients (112).”

What the sources say

• Not checked yetcites [112] Wang, 2016, Genome-wide long noncoding RNA analysis identified circulating lncRNAs as novel noninvasive diagnostic biomarkers for gynecological disease, Sci Rep source