Distinct Local and Systemic Molecular Signatures in the Esophageal and Gastric Cancers: Possible Therapy Targets and Biomarkers for Gastric Cancer

Bednarz−Misa, Iwona; Fortuna, Paulina; Diakowska, Dorota; Jamrozik, Natalia; Krzystek−Korpacka, Małgorzata

doi:10.3390/ijms21124509

Cited by 22 publications

(22 citation statements)

References 46 publications

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“…Regarding the link between receptor expression and overall malignant potential, the changes were occurring in both normal and neoplastic tissue. Of note, it has been repeatedly demonstrated that the macroscopically normal tissue adjacent to tumors might be already altered at the molecular level, preceding histological and morphological changes, in a manner reflecting disease advancement [ 32 , 33 , 34 ]. This phenomenon—referred to as the “tumor molecular margin”—is clinically important as it is held responsible for cancer recurrence following surgery and for the simultaneous occurrence of multiple tumors [ 35 , 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Biphasic Expression of Atypical Chemokine Receptor (ACKR) 2 and ACKR4 in Colorectal Neoplasms in Association with Histopathological Findings

et al. 2020

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Facilitating resolution of inflammation using atypical chemokine receptors (ACKR) as an anticancer strategy is considered but requires a deeper understanding of receptor role in carcinogenesis. We aimed at transcriptional analysis (RTqPCR) of ACKR2 and ACKR4 expression in colorectal adenoma-adenocarcinoma sequence in paired normal-neoplastic tissues from 96 polyps and 51 cancers. On average, ACKR2 was downregulated in neoplastic as compared to non-affected tissue in polyp (by 2.7-fold) and cancer (by 3.1-fold) patients. The maximal downregulation (by 8.2-fold) was observed in adenomas with the highest potential for malignancy and was gradually lessening through cancer stages I-IV, owing to increased receptor expression in tumors. On average, ACKR4 was significantly downregulated solely in adenocarcinomas (by 1.5-fold), less so in patients with lymph node metastasis, owing to a gradual decrease in ACKR4 expression among N0-N1-N2 cancers in non-affected tissue without changes in tumors. In adenomas, ACKR4 downregulation in neoplastic tissue increased with increasing potential for malignancy and contribution of villous growth pattern. ACKR4 expression increased in non-affected tissue with a concomitant decrease in pathological mucosa. In conclusion, the changes in ACKRs expression occur already in precancerous colorectal lesions, culminating in the adenomas with the highest potential for malignancy. Therefore, chemoprevention by manipulating ACKRs’ expression is worth exploration.

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Section: Discussionmentioning

confidence: 99%

Biphasic Expression of Atypical Chemokine Receptor (ACKR) 2 and ACKR4 in Colorectal Neoplasms in Association with Histopathological Findings

et al. 2020

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“…It also corroborates findings of an inverse relationship between tumor infiltration by eosinophils and the metastatic potential of colorectal cancer as well as the progression from adenoma to carcinoma (reviewed in [41]). The 3-NT is considered a footprint of NOS2 activity [5], and NOS2 expression in tumors of the digestive tract is elevated [8][9][10]. Therefore, the inverse 3-NT correlation with lymph node and distant metastasis observed here seems counterintuitive.…”

Section: Discussionmentioning

confidence: 62%

“…The macrophage NOS2 has been implicated in cancer promotion [6,7]. Local NOS2 overexpression has been shown in the digestive tract tumors [8,9], including those in the colon and rectum [10], predicting poor prognosis [11].…”

Section: Introductionmentioning

confidence: 99%

Simultaneous LC-MS/MS-Based Quantification of Free 3-Nitro-l-tyrosine, 3-Chloro-l-tyrosine, and 3-Bromo-l-tyrosine in Plasma of Colorectal Cancer Patients during Early Postoperative Period

et al. 2020

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Quantification with satisfactory specificity and sensitivity of free 3-Nitro-l-tyrosine (3-NT), 3-Chloro-l-tyrosine (3-CT), and 3-Bromo-l-tyrosine (3-BT) in biological samples as potential inflammation, oxidative stress, and cancer biomarkers is analytically challenging. We aimed at developing a liquid chromatography–tandem mass spectrometry (LC-MS/MS)-based method for their simultaneous analysis without an extract purification step by solid-phase extraction. Validation of the developed method yielded the following limits of detection (LOD) and quantification (LOQ) for 3-NT, 3-BT, and 3-CT: 0.030, 0.026, 0.030 ng/mL (LODs) and 0.100, 0.096, 0.098 ng/mL (LOQs). Coefficients of variation for all metabolites and tested concentrations were <10% and accuracy was within 95–105%. Method applicability was tested on colorectal cancer patients during the perioperative period. All metabolites were significantly higher in cancer patients than healthy controls. The 3-NT was significantly lower in advanced cancer and 3-BT showed a similar tendency. Dynamics of 3-BT in the early postoperative period were affected by type of surgery and presence of surgical site infections. In conclusion, a sensitive and specific LC-MS/MS method for simultaneous quantification of free 3-NT, 3-BT, and 3-CT in human plasma has been developed.

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“…As mentioned earlier, it may result from applied antibody being not optimal but may also indicate a cancer-associated accumulation of the interleukin in tumor-adjacent tissue. As has been repeatedly demonstrated [ 22 , 23 , 36 , 37 , 38 ], alterations in molecular profile of still non-transformed cells in tumor vicinity are common and may precede morphological and histological changes. The “tumor molecular margin” phenomenon predispose to neoplastic transformation and accounts for cancer recurrence and the synchronous tumors [ 39 , 40 , 41 ].…”

Section: Discussionmentioning

confidence: 88%

“…Data on relative expression of IL4 , IL4Ra , IL7 , IL7Ra , IL10 , IL10Ra , IL13 , IL13Ra , ACTA2 , BCL2 , BCLxL , CCL2 , CDKN1A , CLDN2 , SLC2A1 , HIF1A , Ki67 , NOS2 , ODC1 , PTGS2 , TJP1 , and VEGFA in tissue samples investigated were available for 45 cancer patients and were retrieved from our earlier studies [ 22 , 23 ] for the purpose of correlation analysis.…”

Section: Methodsmentioning

confidence: 99%

Local and Systemic Interleukin-32 in Esophageal, Gastric, and Colorectal Cancers: Clinical and Diagnostic Significance

Diakowska

Krzystek−Korpacka

2020

Diagnostics

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Little is known on clinical and diagnostic relevance of interleukin-32 in gastrointestinal tract (GIT) cancers. We determined its mRNA (n = 52) and protein (n = 63) expression in paired (tumor-normal) samples from esophageal squamous cell carcinoma (ESCC) and gastric (GC) and colorectal cancer (CRC) patients, with reference to cancer-associated genes, and quantified circulating interleukin-32 in 70 cancer patients and 28 controls. IL32 expression was significantly upregulated solely in ESCC, reflecting T stage in non-transformed tumor-adjacent tissue. Fold-change in IL32 and IL-32 was higher in left-sided CRC, owing to high interleukin expression in non-transformed right-sided colonic mucosa. IL32 was independently and positively associated with Ki67, HIF1A, and ACTA2 and negatively with TJP1 in tumors and with IL10Ra and BCLxL in non-transformed tumor-adjacent tissue. IL-32 protein was significantly upregulated in colorectal tumors. In ESCC, advanced stage and lymph node metastasis were associated with significant IL-32 upregulation. Circulating interleukin was significantly elevated in cancer patients, more so in ESCC and GC than CRC. As biomarker, IL-32 detected gastroesophageal cancers with 99.5% accuracy. In conclusion, IL-32 is upregulated in GIT cancers at local and systemic level, reflecting hypoxia and proliferative and invasive/metastatic capacity in tumors and immunosuppressive and antiapoptotic potential in non-transformed mucosa, while being an accurate biomarker of gastroesophageal cancers.

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Distinct Local and Systemic Molecular Signatures in the Esophageal and Gastric Cancers: Possible Therapy Targets and Biomarkers for Gastric Cancer

Cited by 22 publications

References 46 publications

Biphasic Expression of Atypical Chemokine Receptor (ACKR) 2 and ACKR4 in Colorectal Neoplasms in Association with Histopathological Findings

Biphasic Expression of Atypical Chemokine Receptor (ACKR) 2 and ACKR4 in Colorectal Neoplasms in Association with Histopathological Findings

Simultaneous LC-MS/MS-Based Quantification of Free 3-Nitro-l-tyrosine, 3-Chloro-l-tyrosine, and 3-Bromo-l-tyrosine in Plasma of Colorectal Cancer Patients during Early Postoperative Period

Local and Systemic Interleukin-32 in Esophageal, Gastric, and Colorectal Cancers: Clinical and Diagnostic Significance

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