KRT17 (Keratin 17)

The detection of K17 in 10% or greater of PDAC cells identified patients with shortest survival. Among patients with low K17 PDACs, 5-FU-based treatment was more likely than gemcitabine-based therapies to extend survival.

P1, N=19, Recruiting, Kamari Pharma Ltd | Phase classification: P1b --> P1 | N=11 --> 19 | Trial completion date: Dec 2023 --> Aug 2024 | Trial primary completion date: Dec 2023 --> Aug 2024

P1, N=18, Recruiting, Kamari Pharma Ltd | N=10 --> 18 | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

We found that CK20/CD44/p53, individually or in combination, could not distinguish urothelial neoplasia from non-neoplasia. Full thickness CK17 urothelial localization by immunohistochemistry was highly reproducible with excellent interobserver agreement and may play a supplementary role in distinguishing upper tract urothelial neoplasia from benign urothelium.

XCHD showed the therapeutic effect on psoriasis by regulating keratinocyte differentiation, and suppressing inflammation and angiogenesis, which provided a theoretical basis for further experiments and clinical research.

Limitations include cross-sectional design and convenience sampling. URO17 may improve sensitivity of urine cytology in the detection of urothelial cancer, though further study is required to refine the application of this biomarker in clinical practice.

The largest group included 10 genes: TIMP1, TIMP2, WEE1, YAP, HIF1A, PI3KCA, UTP14A, APIP, PTEN, and SLC26A6. The genetic signatures associated with smoking habits that we have found may serve as a prerequisite for the development of diagnostic panels/tests predicting responses to different therapeutic strategies for HNSCC.

Concerning the second objective, we prospectively analyzed the time courses of EV mRNA markers while NMIBC patients (n = 189) (median follow-up 19 months). The expression of EV mRNA KRT17 was significantly high in patients with recurrence, while it gradually decreased over time in those without recurrence (p < 0.01).

KRT17-high intermediate cell population with elevated CXCL8 expression informed elevated myeloid infiltration status in tumors and associated with pro-tumorigenic signatures in peripheral granulocytes from pancreatic cancer patients. Further, CXCL8 plasma levels were found to resemble KRT17+/CXCL8+ abundance in tumors, in which higher levels predicted worse patient outcomes.

These findings support the substantial role of RHCG in psoriatic inflammation development and suggest that RHCG serves as a potential target for psoriasis treatment.

Combination treatment with onalespib and paclitaxel had an acceptable toxicity profile and showed anti-tumor activity in patients with advanced TNBC. Gene expression analysis of patient tumor samples suggest that TNBCs with greater activation of immune checkpoint pathways and those with proteins dependent on HSP90 activity, including p53 and HER2, may be more susceptible to HSP90 inhibition.ClinicalTrials.gov study identification: NCT02474173

The silenced KRT17 remarkably downregulated the expression of cyclinD1, Cyclin Dependent Kinase 1 (CDK1), CDK2, Phospho-Focal Adhesion Kinase (p-FAK), p-Src, and p-ERK proteins in the PC cells. Generally, an essential signaling cascade of miRNA-485-5p/KRT17/FAK/Src/ERK influences the biological functions of PC cells.

Notably, low KRT17TB can specifically identify those patients with a poor prognosis among colorectal cancer patients with low TB and high T-lymphocyte infiltration. KRT17 can be employed as a new indicator for distinguishing different immunological TBs.

Distinguishing non-muscle invasive subtypes benefits from Keratin 17. Neu5Gc-modified UMOD glycoproteins pose potential in BC diagnosis, while fibronectin, laminin-5, collagen type IV, and lamprey immunity protein in early detection of BC.

Additionally, KGS-high tumor cells exhibited increased sensitivity to several targeted agents, including gefitinib, erlotinib, lapatinib, and trametinib, in comparison to KGS-low cells. This study developed a KGS score that independently predicts the prognosis in LUAD. High expression of KGS score, accompanied by upregulation of TGF-β and WNT-β catenin signaling pathways, confers more aggressive EMT and tumor progression.

Instead, stress keratins are consistently co-regulated with genes with roles in differentiation, inflammation, and/or activation of innate immunity at the single-cell level. These findings provide a roadmap toward explaining the broad diversity and contextual regulation of keratins.

FSTL3 is significantly associated with the prognosis and progression of lung adenocarcinoma and the infiltration of immune cells. Thus, targeting FSTL3 and its associated genes in immunotherapy could be potentially beneficial for the treatment of lung adenocarcinoma.

Keratin 17 but not oral brush cytology can help identify patients with differentiated dysplasia with higher risk for malignant transformation.

Our analysis suggests that K17 is a negative prognostic factor in the majority of studied cancer types, including HPV-associated types such as HNSCC and cervical cancer (13/17), and a positive prognostic factor in 2/17 studied cancer types (urothelial carcinoma of the upper urinary tract and breast cancer). In three out of four predictive studies, K17 was a negative predictive factor for chemotherapy and immune checkpoint blockade therapy response.

Low intensity induction (Lo) included hypomethylating agent with/without venetoclax... The clinical outcomes of TP53 mutated MDS/AML remains discouraging. Select patients may benefit from HSCT but a large proportion of patients still experience post-transplant relapse. Better treatment strategy is direly needed for this distinct patient population.

Gene set enrichment analysis reveals that SGG-induced strong ER- (endoplasmic reticulum) stress and UPR- (unfolded protein response) activation in colonic epithelial cells. Our results suggest that SGG induces a pro-tumoral shift in human colonic cells particularly in transformed cells potentially accelerating tumor development in the colon.

The treatment of SiHa cells with HIV Tat and gp120 proteins induces EMT and activates the Wnt/β-catenin pathway, suggesting that the Wnt/β-catenin pathway may play a crucial role in promoting EMT progression in cervical lesion tissues of HIV-infected patients.

In sum, these strongly concurrent spatial transcriptome and protein data suggest that B7-H3 and the immune suppressive network of ILC may be a promising target for early stage lobular breast cancer. B7-H3 Inhibitors could be explored in the neoadjuvant setting to evaluate the efficacy of immunotherapy in primary ILC.

However, further research is necessary to delve into the differential genomic characteristics that contribute to the unfavorable prognosis observed in patients diagnosed with HR+ EBC before the age of 40. Key clinical and molecular features in 441 biopsies

Through single cell analysis of PDAC samples we identified KRT17High/CXCL8+ cancer cells as an intermediary subtype, marked by a unique cytokine profile and capable of influencing myeloid cells in the tumor microenvironment and systemically. The abundance of this cell population should be considered for patient stratification in precision immunotherapy.

CK17 RNA expression was predictive of PFS and OS in 552 pembrolizumab-treated cancer patients. Our findings indicate that high CK17 expression may predict resistance to ICB in HNSCC patients and beyond.

Conclusions We identified CCL2 and galectin-3 as tumor factors regulated by K17 expression. Validation studies are needed to confirm their protein expressions and their direct role in tumor-macrophage communications.

Among patients receiving pembrolizumab-based therapy (n=21), there were 12 (57...There was no correlation between K17 and individual markers. Conclusions Our findings suggest an inverse trend between K17 expression and clinical outcomes, pending further validation in an expanded patient cohort.

In conclusion, the improved outcomes of pembrolizumab treatment in mUC are restricted to patients with lower NLR. Our findings begin to elucidate a distinct molecular pattern for the presence of TLS according to the NLR in peripheral blood.

The persistence of GATA6 and KRT17 cells post-CTX was significantly associated with poor survival after mFOLFIRINOX (mFFX), but not gemcitabine (GEM), treatment. Analysis of organoid models derived from chemo-naive and post-CTX samples demonstrated that CYP3A expression is a predictor of chemotherapy response and that CYP3A-expressing drug detoxification pathways can metabolize the prodrug irinotecan, a constituent of mFFX. These findings identify CYP3A-expressing drug-tolerant cell phenotypes in residual disease that may ultimately inform adjuvant treatment selection.

KRT17 can inhibit the Wnt/β-catenin signaling pathway, thereby reducing the proliferation and invasion ability of TNBC-Dox-resistant cells.

Western blot analysis revealed a greater differential expression of PGR-A and total progesterone (PGR-A and PGR-B) in tumors from Black compared with tumors from White patients. Collectively, we identified a set of genes uniquely expressed in a race/ethnicity-dependent manner, which could form the underlying mechanisms for the racial disparity in fibroids and their associated symptoms.

In a cohort of patients with colorectal cancer receiving pembrolizumab, high KRT17 expression was found within the tumors of responders. Collectively, we elucidated a critical role of KRT17 in CRC to prevent immune escape. These findings present new insights into potential therapeutic strategies and effective markers of immunotherapy reactivity against pMMR tumors.

Funding: ZonMw (the Netherlands Organisation for Health Research and Delevopment) "Goed Gebruik Geneesmiddelen"-programma, project 848101012.Background: The first-line treatment for metastasized pancreatic ductal adenocarcinoma (PDAC) is a combination treatment with fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX). Our results indicate that the predictive value of transcriptomic subtyping can be translated into a large Dutch real-world cohort, consisting of academic and regional hospitals. Given that only half of the prospectively included patients yielded evaluable biopsies for RNA-sequencing, probably surrogate biomarkers for transcriptome-based subtyping, such as immunohistochemistry, will be more feasible in clinical practice to predict FOLFIRINOX response.

Subsequent analyses indicated that estrogen treatment induces a systemic immunosuppressive state in MmuPV1-infected animals and that both estrogen and K17 modulate the local intratumoral immune microenvironment within MmuPV1-induced neoplastic lesions. Collectively, these findings suggest that estrogen and K17 act at multiple stages of papillomavirus-induced disease at least in part via immunomodulatory mechanisms.

The levels of Matrix-metalloproteinases such as MMP-2, MMP-9 were significantly reduced in CAC mice treated with HQT; The mRNA expression for Krt17, App, CD44 and WNT pathway related sites such as Lrrc15, Cldn-1, Mpc1, Agr2 which are related factors affecting the epithelial mesenchymal transition were significantly reduced in CAC mice treated with HQT; the aberrant mRNA expression of inflammasome components that drive pyroptosis, including Nlrp3, Caspase-1, ASC, GSDMD and its mediated product IL-18 have been improved. Our findings provide preliminary clarification that inhibiting the progression of CAC by using HQT is effective, the mechanism of action may be relatedto the inhibition of epithelial mesenchymal transition and induction of pyroptosis during tumorigenesis.

Furthermore, the rescue assay verified that TP63 could facilitate KRT17 expression to activate the AKT signaling pathway, which in turn stimulated TC cell invasion and migration, and induced EMT. All these results verified that TP63 facilitates TC malignant progression by promoting KRT17 expression and inducing EMT.

Activating driver mutations were identified in invasive cancers only. High mutational load correlated with metastases, which in turn represented clonal disease.

NR120519 activated the AKT/mTOR pathway and EMT by blocking KRT17 to promote cell proliferation and the migration of hypopharyngeal carcinoma.

Keratin 17 is highly expressed in almost all cases of urothelial carcinoma including those of papillary and squamous characteristics, confirming the high sensitivity of K17 in detecting all categories of urothelial carcinoma. Keratin 17 was also observed in many benign and premalignant conditions such as cystitis, PUNLMP, and metaplasia suggesting the K17 expression can result from a trauma to urothelium that could lead to activation of K17 in regenerating urothelial cells. Additional studies are ongoing to confirm and expand the utility of the K17 biomarker in bladder cancer.