CTHRC1 expression is a novel shared diagnostic and prognostic biomarker of survival in six different human cancer subtypes
Nuzhat SialMukhtiar AhmadMuhammad Safdar HussainMuhammad Junaid IqbalYasir HameedMehran KhanMustansar AbbasAsif RizwanJalil Ur RehmanMuhammad AtifMuhammad Rashid KhanZahid HameedHina SaeedRida TanveerSaba SaeedAneeqa SharifHafiz Muhammad Asif
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According to the previous reports, the collagen triple helix repeat containing 1 (CTHRC1) causes tumorigenesis by modulating the tumor microenvironment, however, the evidence is limited to a few human cancer subtypes. In the current study, we analyzed and validated the CTHRC1 expression variations in 24 different human cancer tissues paired with normal tissues using publically available databases. We observed that CTHRC1 was overexpressed in all the 24 major subtypes of human cancers and its overexpression was significantly associated with the reduced overall survival (OS) duration of head and neck squamous cell carcinoma (HNSC), kidney renal clear cell carcinoma (KIRC), liver hepatocellular carcinoma (LIHC), Lung adenocarcinoma (LUAD), stomach adenocarcinoma (STAD), and Uterine corpus endometrial carcinoma (UCEC). This implies that CTHRC1 plays a significant role in the development and progression of these cancers. We further noticed that CTHRC1 was also overexpressed in HNSC, KIRC, LIHC, LUAD, STAD, and UCEC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of CTHRC1 associated genes in seven diverse pathways. We also explored few interesting correlations between CTHRC1 expression and promoter methylation, genetic alterations, CNVs, CD8+ T immune cells infiltration, and tumor purity. In conclusion, CTHRC1 can serve as a shared diagnostic and prognostic biomarker in HNSC, KIRC, LIHC, LUAD, STAD, and UCEC patients of different clinicopathological features.Keywords:
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Abstract Background & Aims Currently, using biopsy specimens to confirm suspicious liver lesions of early hepatocellular carcinoma are not entirely reliable because of insufficient sampling amount and inaccurate sampling location. It is necessary to develop a signature to aid early hepatocellular carcinoma diagnosis using biopsy specimens even when the sampling location is inaccurate. Methods Based on the within‐sample relative expression orderings of gene pairs, we identified a simple qualitative signature to distinguish both hepatocellular carcinoma and adjacent non‐tumour tissues from cirrhosis tissues of non‐hepatocellular carcinoma patients. Results A signature consisting of 19 gene pairs was identified in the training data sets and validated in 2 large collections of samples from biopsy and surgical resection specimens. For biopsy specimens, 95.7% of 141 hepatocellular carcinoma tissues and all (100%) of 108 cirrhosis tissues of non‐hepatocellular carcinoma patients were correctly classified. Especially, all (100%) of 60 hepatocellular carcinoma adjacent normal tissues and 77.5% of 80 hepatocellular carcinoma adjacent cirrhosis tissues were classified to hepatocellular carcinoma. For surgical resection specimens, 99.7% of 733 hepatocellular carcinoma specimens were correctly classified to hepatocellular carcinoma, while 96.1% of 254 hepatocellular carcinoma adjacent cirrhosis tissues and 95.9% of 538 hepatocellular carcinoma adjacent normal tissues were classified to hepatocellular carcinoma. In contrast, 17.0% of 47 cirrhosis from non‐hepatocellular carcinoma patients waiting for liver transplantation were classified to hepatocellular carcinoma, indicating that some patients with long‐lasting cirrhosis could have already gained hepatocellular carcinoma characteristics. Conclusions The signature can distinguish both hepatocellular carcinoma tissues and tumour‐adjacent tissues from cirrhosis tissues of non‐hepatocellular carcinoma patients even using inaccurately sampled biopsy specimens, which can aid early diagnosis of hepatocellular carcinoma.
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Foreword. Preface. 1. The background to hepatocellular carcinoma and the liver. 2. Premalignant lesions of hepatocellular carcinoma. 3. Pathomorphologic characteristics of early-stage small hepatocellular carcinoma. 4. Morphologic evolution of hepatocellular carcinoma: from early to advanced. 5. Angioarchitecture of hepatocellular carcinoma. 6. Advanced hepatocellular carcinoma. 7. Multicentric occurrence of hepatocellular carcinoma. 8. Combined hepatocellular carcinoma and cholangiocarcinoma. 9. Nodular lesions mimicking hepatocellular carcinoma. 10. Biopsy diagnosis of tumorous lesions of the liver. 11. Chemoprevention of hepatocellular carcinoma. Index
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Hepatocellular carcinoma is the most common malignancy among males and the 7th among female patients in the Kingdom of Saudi Arabia. This is due to the endemicity of hepatitis B and hepatitis C. Spontaneous rupture of hepatocellular carcinoma is rare. We report 4 cases of spontaneous rupture of hepatocellular carcinoma. Initial control of bleeding was achieved surgically in 3 patients and by embolization in the 4th patient. All patients had very good hepatic reserve as reflected by Child-Pugh scoring (A & B). We found that the incidence of ruptured hepatocellular carcinoma among 85 patients was 4.7%. The prognosis of this subgroup of patients is poor as reflected by the low median survival ranging from 6-16 weeks.
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The problem and approaches to the treatment of hepatocellular carcinoma as seen in Japan are reported. Current Japanese methods for the detection of hepatocellular carcinoma and the methods used to treat hepatocellular carcinoma are described. Included in the latter discussion is a description of the untoward effects of each treatment. Finally an alogorithm for the treatment of hepatocellular carcinoma is presented based upon the Japanese experience.
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Orthotopic liver transplant is the treatment of choice for hepatocellular carcinoma in cirrhotic patients with satisfactory oncologic and survival outcomes. Incidental hepatocellular carcinoma is frequently a reported finding in the explant pathology after orthotopic liver transplant.The present study retrospectively analyzed the tumor characteristics and outcomes of 50 incidental hepatocellular carcinomas compared with 252 transplants for known hepatocellular carcinoma.Patients with incidental hepatocellular carcinoma had lower peak alpha-fetoprotein level (P = .001), lower pretransplant alpha-fetoprotein level (P = .002), smaller total tumor size (P = .0001), fewer tumor numbers (P = .0001), lower level of microvascular invasion (P = .001), more cases within Milan criteria (P = .005), and more well-differentiated tumors (P = .017). However, no difference in survival rates was observed between the 2 groups. In 35 patients (70%) who had incidental hepatocellular carcinoma, pretransplant imaging studies were normal; ultrasonography was used as the only screening tool in 25 of 35 patients (71%) who had incidental hepatocellular carcinoma, and 15 patients (30%) who had incidental hepatocellular carcinoma had regenerative or dysplastic nodules. The accuracy of ultrasonography in our unit for diagnosing hepatocellular carcinoma was 97.5%. A quarter of hepatitis B recipients had incidental hepatocellular carcinoma with a younger median recipient age. Tumor recurrence was higher with incidental hepatocellular carcinoma in hepatitis C recipients (22%). However, the overall recurrence was similar between all hepatitis and nonhepatitis recipients who were transplanted for incidental or known hepatocellular carcinoma.Incidental hepatocellular carcinoma has similar outcome as known hepatocellular carcinoma. Early screening of hepatitis B patients is recommended, and cross-sectional imaging is not mandatory for hepatocellular carcinoma screening in patients who are on the waiting list.
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Direct acting antivirals stabilize or improve liver function in the majority of patients with hepatitis C virus cirrhosis. Hepatic decompensation is the main driver of death of patients with early, successfully treated hepatocellular carcinoma superimposed to cirrhosis. Treatment with direct acting antivirals could improve the prognosis of these subjects, independently from the subsequent course of hepatocellular carcinoma, if the efficacy in obtaining viral clearance is as high as in patients without a history of hepatocellular carcinoma, and if the risk of hepatocellular carcinoma recurrence is unaffected. When dealing with hepatocellular carcinoma patients, direct acting antivirals can be indicated in two different settings: (a) subjects in which hepatocellular carcinoma has been already successfully treated ("cured" hepatocellular carcinoma), or (b) subjects whose hepatocellular carcinoma is still untreated or untreatable ("active" hepatocellular carcinoma). Although there are abundant data on "cured" hepatocellular carcinoma, evidence supporting treatment decisions in patients with "active" hepatocellular carcinoma is at best scarce and controversial, since these patients as well as patients with hepatocellular carcinoma listed for liver transplantation are usually excluded from treatment.
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The aim of this study was to determine the characteristics of hepatocellular carcinoma at a major health center in southern Turkey. Computed tomography was compared to the combination of ultrasonography and serum alpha-fetoprotein determination in the diagnosis of hepatocellular carcinoma.Of 226 patients with liver cirrhosis, 35 were diagnosed with hepatocellular carcinoma on first admission or during follow-up in the period between 1999 and 2002. The features investigated were, age at time of hepatocellular carcinoma diagnosis, etiology of cirrhosis, severity of cirrhosis at presentation, tumor pattern, stage of hepatocellular carcinoma, serum alpha-fetoprotein level, and dynamic computed tomography findings. Results were compared to previous findings in Turkey and elsewhere.In the hepatocellular carcinoma patients, the male:female ratio was 4:1 and the mean age at presentation was 61 years. Chronic hepatitis B virus infection (65.7%) and chronic hepatitis C virus infection (28.6%) were the most frequently identified risk factors for hepatocellular carcinoma. Forty percent of the patients had Child-Pugh A cirrhosis when they were diagnosed with hepatocellular carcinoma. Sixty-seven percent of patients had fewer than three hepatocellular carcinoma nodules in the liver at the time of diagnosis. Only three of the hepatocellular carcinoma cases were Okuda stage I. The combination of ultrasonography and serum alpha-fetoprotein >20 ng/ml identified hepatocellular carcinoma in 32 of the 35 total cases.The results indicate that hepatitis B virus infection in patients with cirrhosis is still the leading risk factor for the development of hepatocellular carcinoma. Also, early-stage hepatocellular carcinoma is rarely diagnosed in cirrhosis patients from this region of Turkey. Surveillance with computed tomography for early diagnosis of hepatocellular carcinoma seems not to be mandatory.
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Objective To evaluate serum AFP levels and their influence factors in patients with hepatocellular carcinoma.Methods From January 1995 to December 1999,140 patients were subjected to hepatectomy in our hospital,AFP levels of the patients were evaluated.The data of the patients were analyzed by nonconditional logistic regression with SPSS10.0.Results The positive rate of AFP was 62.9% in patients with hepatocellular carcinoma.The positive rate of AFP of small hepatocellular carcinoma(52.0%) was significantly higher than that of large hepatocellular carcinoma (73.9%) ( P 0.05).It was showed that the AFP levels were related to tumor size and cirrhosis through logistic regression( P 0.05).Conclusion Sensitivity of AFP in hepatocellular carcinoma diagnosis,especially in small hepatocellular cancer was lower.It was notably increased when combined with other diagnostic methods.
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